Halogenated anti-infective agent that is used against trematode and cestode infestations.
A phenol obtained from thyme oil or other volatile oils used as a stabilizer in pharmaceutical preparations, and as an antiseptic (antibacterial or antifungal) agent. It was formerly used as a vermifuge.
Reduction of pharmacologic activity or toxicity of a drug or other foreign substance by a living system, usually by enzymatic action. It includes those metabolic transformations that make the substance more soluble for faster renal excretion.
Functionalization of exogenous substances to prepare them for conjugation in PHASE II DETOXIFICATION. Phase I enzymes include CYTOCHROME P450 enzymes and some OXIDOREDUCTASES. Excess induction of phase I over phase II detoxification leads to higher levels of FREE RADICALS that can induce CANCER and other cell damage. Induction or antagonism of phase I detoxication is the basis of a number of DRUG INTERACTIONS.
The conjugation of exogenous substances with various hydrophilic substituents to form water soluble products that are excretable in URINE. Phase II modifications include GLUTATHIONE conjugation; ACYLATION; and AMINATION. Phase II enzymes include GLUTATHIONE TRANSFERASE and GLUCURONOSYLTRANSFERASE. In a sense these reactions detoxify phase I reaction products.
A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.
A group of mental disorders associated with organic brain damage and caused by poisoning from alcohol.
The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.
Nitro-phenanthrenes occurring in ARISTOLOCHIACEAE and other plants. They derive from stephanine (APORPHINES) by oxidative ring cleavage. The nitro group is a reactive alkylator (ALKYLATING AGENTS) that binds to biological macromolecules. Ingestion by humans is associated with nephropathy (NEPHRITIS). There is no relationship to the similar named aristolochene (SESQUITERPENES).
Pigment obtained by the oxidation of epinephrine.
A potent hepatotoxic and hepatocarcinogenic mycotoxin produced by the Aspergillus flavus group of fungi. It is also mutagenic, teratogenic, and causes immunosuppression in animals. It is found as a contaminant in peanuts, cottonseed meal, corn, and other grains. The mycotoxin requires epoxidation to aflatoxin B1 2,3-oxide for activation. Microsomal monooxygenases biotransform the toxin to the less toxic metabolites aflatoxin M1 and Q1.
Aminopyrine N-Demethylase is an enzyme, specifically a cytochrome P450 isoform, involved in the metabolism of drugs and xenobiotics, responsible for catalyzing the N-demethylation reaction.
A liver microsomal cytochrome P-450 monooxygenase capable of biotransforming xenobiotics such as polycyclic hydrocarbons and halogenated aromatic hydrocarbons into carcinogenic or mutagenic compounds. They have been found in mammals and fish. This enzyme, encoded by CYP1A1 gene, can be measured by using ethoxyresorufin as a substrate for the ethoxyresorufin O-deethylase activity.
Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.
A flavoprotein that reversibly catalyzes the oxidation of NADH or NADPH by various quinones and oxidation-reduction dyes. The enzyme is inhibited by dicoumarol, capsaicin, and caffeine.
A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke.
A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.
The products of chemical reactions that result in the addition of extraneous chemical groups to DNA.
Agents that reduce the frequency or rate of spontaneous or induced tumors independently of the mechanism involved.
Substituted thioglucosides. They are found in rapeseed (Brassica campestris) products and related cruciferae. They are metabolized to a variety of toxic products which are most likely the cause of hepatocytic necrosis in animals and humans.
Organic derivatives of thiocyanic acid which contain the general formula R-SCN.
A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.
Carboxylesterase is a serine-dependent esterase with wide substrate specificity. The enzyme is involved in the detoxification of XENOBIOTICS and the activation of ester and of amide PRODRUGS.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
A cytochrome P450 enzyme subtype that has specificity for relatively planar heteroaromatic small molecules, such as CAFFEINE and ACETAMINOPHEN.
Organic compounds with the general formula R-NCS.
An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.
Pyrazines are heterocyclic organic compounds containing a six-membered ring with two nitrogen atoms at opposite positions, often responsible for the characteristic flavors and aromas found in various foods, beverages, and some biological systems, but they do not have a direct medical definition as they are not a drug, treatment, or a significant component of human physiology or pathology.
Enzymes which catalyze the hydrolysis of carboxylic acid esters with the formation of an alcohol and a carboxylic acid anion.
Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.
A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.
F344 rats are an inbred strain of albino laboratory rats (Rattus norvegicus) that have been widely used in biomedical research due to their consistent and reliable genetic background, which facilitates the study of disease mechanisms and therapeutic interventions.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
The rate dynamics in chemical or physical systems.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.

Methemoglobin formation by hydroxylamine metabolites of sulfamethoxazole and dapsone: implications for differences in adverse drug reactions. (1/796)

Differences in the incidence of adverse drug reactions to trimethoprim-sulfamethoxazole and dapsone may result from differences in the formation, disposition, toxicity, and/or detoxification of their hydroxylamine metabolites. In this study, we examine whether differences in the biochemical processing of sulfamethoxazole hydroxylamine (SMX-NOH) and dapsone hydroxylamine (DDS-NOH) by erythrocytes [red blood cells (RBCs)] contribute to this differential incidence. The methemoglobin (MetHgb)-forming capacity of both metabolites was compared after a 60-min incubation with washed RBCs from four healthy human volunteers. DDS-NOH was significantly more potent (P =.004) but equally efficacious with SMX-NOH in its ability to form MetHgb. The elimination of potential differences in disposition by lysing RBCs did not change the MetHgb-forming potency of either hydroxylamine. At pharmacologically relevant concentrations, greater reduction to the parent amine occurred with DDS-NOH. Maintenance of MetHgb-forming potency was dependent on recycling with glutathione, but no difference in cycling efficiency was observed between DDS-NOH and SMX-NOH. In contrast, the pharmacodynamics of hydroxylamine-induced MetHgb formation were not changed by pretreatment with the glucose 6-phosphate dehydrogenase inhibitor epiandrosterone or by compounds that alter normal antioxidant enzyme activity. Methylene blue, which stimulates NADPH-dependent MetHgb reductase activity, decreased MetHgb levels but did not alter the differential potency of these hydroxylamines. DDS-NOH was also significantly more potent when incubated with purified human hemoglobin A0. Collectively, these data suggest that the inherently greater reactivity of DDS-NOH with hemoglobin, the greater conversion of DDS-NOH to its parent amine, and potential differences in disposition of hydroxylamine metabolites may contribute to the preferential development of dapsone-induced hemotoxicity and sulfamethoxazole-induced hypersensitivity reactions.  (+info)

Glutathione S-transferase GSTM3 and GSTP1 genotypes and larynx cancer risk. (2/796)

Glutathione S-transferases (GSTs) are involved in detoxification of reactive metabolites of carcinogens and, therefore, could be potentially important in susceptibility to cancer. The associations between larynx cancer risk and GSTM3 and GSTP1 gene polymorphisms, either separately or in combination with GSTM1 and GSTT1 gene polymorphisms, were evaluated using peripheral blood DNA from 129 cancer patients and 172 controls, all regular smokers. The frequencies of GSTM3 AA, AB, and BB genotypes were 60.5%, 36.4%, and 3.1% in cases and 72.7%, 24.4%, and 2.9% in controls, respectively. The frequencies of GSTP1 AA, AG, and GG genotypes were 48.1%, 40.3%, and 11.6% in cases and 50.0%, 37.2%, and 12.8% in controls, respectively. Multivariate logistic regression analyses did not reveal any association between the GSTP1 (AG or GG) genotype and larynx cancer [odds ratio, 1.1; 95% confidence interval (CI), 0.7-2.0]. In contrast, a significant increase in risk was related to the GSTM3 (AB or BB) genotype (odds ratio, 2.0; 95% CI, 1.1-3.4). The combined GSTM3 (AB or BB) and GSTM1-null genotype conferred a 4-fold risk (95% CI, 1.6-10.1) of larynx cancer as compared with the combined GSTM3 AA and GSTM1-positive genotype. However, the effect of GSTM3 (AB or BB) genotype was similar among individuals with GSTM1-positive or GSTM1-null genotypes.  (+info)

Pregnenolone esterification in Saccharomyces cerevisiae. A potential detoxification mechanism. (3/796)

While studying the effect of steroids on the growth of the yeast Saccharomyces cerevisiae, we found that pregnenolone was converted into the acetate ester. This reaction was identified as a transfer of the acetyl group from acetyl-CoA to the 3beta-hydroxyl group of pregnenolone. The corresponding enzyme, acetyl-CoA:pregnenolone acetyltransferase (APAT) is specific for Delta5- or Delta4-3beta-hydroxysteroids and short-chain acyl-CoAs. The apparent Km for pregnenolone is approximately 0.5 microm. The protein associated with APAT activity was partially purified and finally isolated from an SDS/polyacrylamide gel. Tryptic peptides were generated and N-terminally sequenced. Two peptide sequences allowed the identification of an open reading frame (YGR177c, in the S. cerevisiae genome database) translating into a 62-kDa protein of hitherto unknown function. This protein encoded by a gene known as ATF2 displays 37% identity with an alcohol acetyltransferase encoded by the yeast gene ATF1. Disruption of ATF2 led to the complete elimination of APAT activity and consequently abolished the esterification of pregnenolone. In addition, a toxic effect of pregnenolone linked to the disruption of ATF2 was observed. Pregnenolone toxicity is more pronounced when the atf2-Delta mutation is introduced in a yeast strain devoid of the ATP-binding cassette transporters, PDR5 and SNQ2. Our results suggest that Atf2p (APAT) plays an active role in the detoxification of 3beta-hydroxysteroids in association with the efflux pumps Pdr5p and Snq2p.  (+info)

Relation of structure of curcumin analogs to their potencies as inducers of Phase 2 detoxification enzymes. (4/796)

A series of naturally occurring as well as synthetic structural analogs of the dietary constituent curcumin were examined in order to elucidate which portions of the molecule are critical for the ability to induce Phase 2 detoxification enzymes in murine hepatoma cells, and hence to assess the chemoprotective potential of these compounds. Two groups of compounds were studied: classical Michael reaction acceptors such as curcumin and related beta-diketones such as dibenzoylmethane which lack direct Michael reactivity. The presence of two structural elements was found to be required for high inducer potency: (i) hydroxyl groups at ortho-position on the aromatic rings and (ii) the beta-diketone functionality. All curcuminoids elevate the specific activity of quinone reductase in both wild type and mutant cells defective in either the aryl hydrocarbon (Ah) receptor or cytochrome P4501A1 activity. This indicates that neither binding to this receptor, nor metabolic activation by P4501A1 are required for the signaling process originating from this family of electrophiles and ultimately resulting in Phase 2 enzyme induction.  (+info)

Molecular basis for hepatic detoxifying enzyme induction by 2-(allylthio)pyrazine in rats in comparison with oltipraz: effects on prooxidant production and DNA degradation. (5/796)

The expression of hepatic microsomal epoxide hydrolase (mEH) and glutathione S-transferases (GSTs) by 2-(allylthio)pyrazine (2-AP), an experimental chemopreventive agent, was investigated in rats. Northern blot analysis revealed that 2-AP caused increases in mEH, rGSTA2/3/5, and rGSTM1/2 mRNA levels. mEH and rGSTA2 proteins were also induced. Molecular basis of the enzyme induction by 2-AP was studied in comparison with oltipraz (Olt). Rats exposed to buthionine sulfoximine, a GSH-depleting agent, before treatment with either 2-AP or Olt exhibited greater increases in the mRNA levels than the individual treatment. Conversely, increases of the mRNAs were prevented by cysteine treatment, indicating that metabolic intermediates or reactive oxygens produced from the agents could be reduced by cysteine. Gel shift analysis revealed that nuclear factor-kappaB, which is associated with the altered cellular redox state, was not activated by the agents. Effects of these agents on the breakage of phix-174 DNA were compared in vitro. 2-AP effectively reduced the conversion of supercoiled DNA to the open circular form induced by benzenetriol and prevented benzenetriol- and iron-catalyzed degradation of DNA, whereas Olt failed to prevent strand breakage of DNA. These results provided evidence that: 1) 2-AP was effective in elevating the hepatic mEH and GST gene expression in rats, which might be mediated with the production of reactive oxygen species; 2) nuclear factor-kappaB activation was not involved in the induction of the detoxifying enzymes by either 2-AP or Olt in spite of their production of reactive oxygens in vivo; and 3) the antioxidant effect of 2-AP in vitro differed from that of Olt.  (+info)

Tolerance to toxic metals by a gene family of phytochelatin synthases from plants and yeast. (6/796)

Phytochelatins play major roles in metal detoxification in plants and fungi. However, genes encoding phytochelatin synthases have not yet been identified. By screening for plant genes mediating metal tolerance we identified a wheat cDNA, TaPCS1, whose expression in Saccharomyces cerevisiae results in a dramatic increase in cadmium tolerance. TaPCS1 encodes a protein of approximately 55 kDa with no similarity to proteins of known function. We identified homologs of this new gene family from Arabidopsis thaliana, Schizosaccharomyces pombe, and interestingly also Caenorhabditis elegans. The Arabidopsis and S.pombe genes were also demonstrated to confer substantial increases in metal tolerance in yeast. PCS-expressing cells accumulate more Cd2+ than controls. PCS expression mediates Cd2+ tolerance even in yeast mutants that are either deficient in vacuolar acidification or impaired in vacuolar biogenesis. PCS-induced metal resistance is lost upon exposure to an inhibitor of glutathione biosynthesis, a process necessary for phytochelatin formation. Schizosaccharomyces pombe cells disrupted in the PCS gene exhibit hypersensitivity to Cd2+ and Cu2+ and are unable to synthesize phytochelatins upon Cd2+ exposure as determined by HPLC analysis. Saccharomyces cerevisiae cells expressing PCS produce phytochelatins. Moreover, the recombinant purified S.pombe PCS protein displays phytochelatin synthase activity. These data demonstrate that PCS genes encode phytochelatin synthases and mediate metal detoxification in eukaryotes.  (+info)

Candidate genetic modifiers of individual susceptibility to renal cell carcinoma: a study of polymorphic human xenobiotic-metabolizing enzymes. (7/796)

The steady increase in sporadic renal cell carcinoma (RCC) observed in industrialized countries supports the notion that certain carcinogens present in the environment (tobacco smoke, drugs, pollutants, and dietary constituents) may affect the occurrence of RCC. Many of the enzymes dealing with such environmental factors are polymorphic and may, therefore, confer variable susceptibility to RCC. This case-control study was designed to test for an association between genetic polymorphism of enzymes involved in xenobiotic metabolism and the risk of sporadic RCC. Genomic DNA was obtained from 173 patients with RCC and 211 controls of Caucasian origin. We used PCR-RFLP to investigate polymorphism for the most common alleles at two cytochrome-P450 mono-oxygenases (CYP1A1 and CYP2D6), one NAD[P]H:quinone oxidoreductase (NQO1), three glutathione S-transferases (GSTM1, GSTT1, and GSTP1), and one N-acetyltransferase (NAT2) loci. The CYP1A1 (m) "variant" genotype, which contains at least one copy of the CYP1A1 variant alleles, was found to be associated with a 2.1-fold [95% confidence interval (CI), 1.1-3.9] increase in the risk of RCC. There was also a higher risk of RCC for subjects with the CYP1A1 (m) variant genotype combined with any of the following genotypes: GSTT1 (+) "active" [odds ratio (OR), 2.3; 95% CI, 1.2-4.5], GSTP1 (m) variant (OR, 2.4; 95% CI, 1.0-5.4), or NAT2 (-) "slow acetylator" (OR, 2.5; 95% CI, 1.1-5.5). A significant association was also found for the GSTM1 (-) "null" and GSTP1 (m) genotypes combined with either NAT2 (-) (OR, 2.6; 95% CI, 1.2-5.8) or CYP1A1 (m) (OR, 3.5; 95% CI, 1.1-11.2). The CYP2D6 (-) "poor metabolizer " and the NQO1 (-) "defective" genotypes were not clearly associated with a higher risk of RCC. Our data demonstrate for the first time a significant association between a group of pharmacogenetic polymorphisms and RCC risk. These positive findings suggest that interindividual variation in the metabolic pathways involved in the functionalization and detoxification of specific xenobiotics is an important susceptibility factor for RCC in Caucasians.  (+info)

Genetic and dietary predictors of CYP2E1 activity: a phenotyping study in Hawaii Japanese using chlorzoxazone. (8/796)

Cytochrome P4502E1 (CYP2E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitrosoamines and low molecular weight organic compounds. An RsaI polymorphism is present in the 5'-flanking region of the CYP2E1 gene, which could possibly affect its transcription. However, the relationship between genotype and the phenotypic catalytic activity of the enzyme has not been defined. Also, the effects in humans of specific dietary factors, other than ethanol, which have been shown in animal and in vitro studies to modulate CYP2E1 activity, are unknown. Accordingly, the CYP2E1-mediated metabolism of chlorzoxazone to its 6-hydroxy metabolite was investigated in 50 healthy Japanese of both sexes in Hawaii. The oral clearance of the in vivo probe, the trait measure of CYP2E1 activity, was smaller than that reported in European-Americans. Significantly, after adjustment for age and sex, the oral clearance of chlorzoxazone decreased with the number of variant c2 alleles, and its mean in the c2/c2 genotype (147 ml/min) was statistically lower (P < or = 0.05) than that for either the homozygous wild-type (238 ml/min) or the heterozygote (201 ml/min) genotypes. Stepwise multiple regression analysis indicated that body weight was a major contributor to the interindividual variability in the oral clearance of chlorzoxazone, accounting for 43% of the variance. Consumption of lettuce, broccoli, and black tea explained additional components of the variability (7, 5, and 6%, respectively), as did medication use (3%), age (4%), and CYP2E1 genotype (5%). Overall, 73% of the variance could be accounted for by these variables. Body weight, lettuce, and use of medications were associated with increased CYP2E1 activity, and the other covariates were associated with reduced enzyme function. Because of the role that CYP2E1 plays in procarcinogen activation, especially of N-nitrosamines involved in lung cancer, the identified factors may account in part for observed differences in individual susceptibility to disease and may also have implications for cancer prevention.  (+info)

Bithionol is an oral antiparasitic medication that has been used to treat infections caused by certain types of tapeworms, such as Paragonimus westermani (lung fluke) and Fasciolopsis buski (intestinal fluke). It works by inhibiting the metabolic processes of the parasites, which helps to eliminate them from the body.

Bithionol is no longer commonly used due to the availability of safer and more effective antiparasitic drugs. Its use may be associated with several side effects, including nausea, vomiting, diarrhea, abdominal pain, dizziness, and skin rashes. In some cases, it may also cause liver damage or allergic reactions.

It is important to note that bithionol should only be used under the supervision of a healthcare professional, as its use requires careful monitoring and dosage adjustment based on the patient's response to treatment.

Thymol is not a medical condition or term, but rather it's an organic compound that is commonly used in the medical and pharmaceutical fields. Thymol is a natural monoterpene phenol derivative of cymene, found in oil of thyme and other essential oils. It has antiseptic, antibiotic, and antifungal properties, which makes it useful as a disinfectant and preservative in various medical and dental applications.

In some contexts, thymol may be used to treat conditions related to fungal or bacterial infections, but it is not typically used as a standalone treatment. Instead, it's often combined with other active ingredients in medications such as mouthwashes, throat lozenges, and topical creams.

It's important to note that thymol should be used under the guidance of a healthcare professional, as its misuse or overuse can lead to adverse effects.

Metabolic detoxification, in the context of drugs, refers to the series of biochemical processes that the body undergoes to transform drugs or other xenobiotics into water-soluble compounds so they can be excreted. This process typically involves two phases:

1. Phase I Detoxification: In this phase, enzymes such as cytochrome P450 oxidases introduce functional groups into the drug molecule, making it more polar and reactive. This can result in the formation of metabolites that are less active than the parent compound or, in some cases, more toxic.

2. Phase II Detoxification: In this phase, enzymes such as glutathione S-transferases, UDP-glucuronosyltransferases, and sulfotransferases conjugate these polar and reactive metabolites with endogenous molecules like glutathione, glucuronic acid, or sulfate. This further increases the water solubility of the compound, allowing it to be excreted by the kidneys or bile.

It's important to note that while these processes are essential for eliminating drugs and other harmful substances from the body, they can also produce reactive metabolites that may cause damage to cells and tissues if not properly regulated. Therefore, maintaining a balance in the activity of these detoxification enzymes is crucial for overall health and well-being.

Metabolic detoxification, Phase I, also known as biotransformation, is the first step in the body's process of breaking down and eliminating potentially harmful substances. This phase involves a group of enzymes, primarily found in the endoplasmic reticulum of cells in the liver, that chemically modify lipophilic (fat-soluble) toxic substances into more hydrophilic (water-soluble) intermediates. These intermediate metabolites are often more reactive and potentially toxic than the original substance, which makes Phase II detoxification crucial for further neutralization and elimination.

The main enzyme systems involved in Phase I detoxification include:

1. Cytochrome P450 (CYP450) mixed-function oxidases: These enzymes catalyze oxidation, reduction, and hydrolysis reactions, introducing polar functional groups such as hydroxyl (-OH), carboxyl (-COOH), or amino (-NH2) groups into the toxic substance.
2. Flavin-containing monooxygenases (FMO): These enzymes catalyze oxidation reactions, primarily introducing oxygen atoms into substrates.
3. Alcohol and aldehyde dehydrogenases: These enzymes catalyze the oxidation of alcohols to aldehydes or ketones, which can then be further metabolized in Phase II detoxification.
4. Epoxide hydrolases: These enzymes catalyze the hydrolysis of epoxides (three-membered rings containing a single oxygen atom) into diols (two hydroxyl groups), reducing their reactivity and toxicity.

It is important to note that some Phase I metabolites can be more harmful than the original substance, so an efficient and balanced Phase II detoxification process is essential for overall health and well-being. Additionally, certain factors such as genetics, age, lifestyle, environmental exposures, and nutritional status can influence the efficiency and capacity of Phase I detoxification.

Metabolic Detoxification, Phase II, also known as conjugation, is the second step in the body's process of neutralizing and eliminating potentially harmful substances. During this phase, the liver cells add a molecule, such as glucuronic acid, sulfuric acid, glycine, or glutathione, to the substance, which has been previously modified during Phase I. This conjugation makes the substance water-soluble, allowing it to be excreted from the body through urine or bile.

In this process, various enzymes, such as UDP-glucuronosyltransferases (UGTs), sulfotransferases (SULTs), N-acetyltransferases (NATs), glutathione S-transferases (GSTs), and methyltransferases, play a crucial role in the transfer of these molecules to the substrate. Proper functioning of Phase II detoxification is essential for the effective elimination of drugs, environmental toxins, endogenous waste products, and other harmful substances from the body.

Glutathione transferases (GSTs) are a group of enzymes involved in the detoxification of xenobiotics and endogenous compounds. They facilitate the conjugation of these compounds with glutathione, a tripeptide consisting of cysteine, glutamic acid, and glycine, which results in more water-soluble products that can be easily excreted from the body.

GSTs play a crucial role in protecting cells against oxidative stress and chemical injury by neutralizing reactive electrophilic species and peroxides. They are found in various tissues, including the liver, kidneys, lungs, and intestines, and are classified into several families based on their structure and function.

Abnormalities in GST activity have been associated with increased susceptibility to certain diseases, such as cancer, neurological disorders, and respiratory diseases. Therefore, GSTs have become a subject of interest in toxicology, pharmacology, and clinical research.

Alcoholic psychosis is a term used to describe a group of psychiatric disorders that are directly related to alcohol abuse or withdrawal. The two most common types of alcoholic psychosis are Wernicke's encephalopathy and Korsakoff's syndrome, which often occur together and are referred to as Wernicke-Korsakoff syndrome.

Wernicke's encephalopathy is a acute neurological disorder characterized by confusion, memory loss, difficulty with muscle coordination, and abnormal eye movements. It is caused by a thiamine (vitamin B1) deficiency that is often seen in people who are chronic alcoholics.

Korsakoff's syndrome, on the other hand, is a chronic memory disorder characterized by severe memory loss and confusion. People with Korsakoff's syndrome often have difficulty learning new information and may confabulate, or make up information, to fill in gaps in their memory.

Both Wernicke's encephalopathy and Korsakoff's syndrome are serious conditions that require immediate medical attention. Treatment typically involves administering thiamine and other vitamins, as well as providing supportive care to help manage symptoms. In some cases, hospitalization may be necessary.

It is important to note that alcohol abuse can also lead to other types of psychosis, such as delirium tremens (DTs), which is a severe form of alcohol withdrawal that can cause confusion, hallucinations, and seizures. If you or someone you know is struggling with alcohol abuse, it is important to seek professional help as soon as possible.

Biotransformation is the metabolic modification of a chemical compound, typically a xenobiotic (a foreign chemical substance found within an living organism), by a biological system. This process often involves enzymatic conversion of the parent compound to one or more metabolites, which may be more or less active, toxic, or mutagenic than the original substance.

In the context of pharmacology and toxicology, biotransformation is an important aspect of drug metabolism and elimination from the body. The liver is the primary site of biotransformation, but other organs such as the kidneys, lungs, and gastrointestinal tract can also play a role.

Biotransformation can occur in two phases: phase I reactions involve functionalization of the parent compound through oxidation, reduction, or hydrolysis, while phase II reactions involve conjugation of the metabolite with endogenous molecules such as glucuronic acid, sulfate, or acetate to increase its water solubility and facilitate excretion.

Aristolochic acids are a group of naturally occurring chemical compounds that are found in certain plants of the Aristolochiaceae family, including Aristolochia and Asarum species. These compounds have been identified as nephrotoxic (kidney-damaging) and carcinogenic (cancer-causing) agents in humans and animals.

Aristolochic acids are present in the roots, rhizomes, and fruits of these plants, and they have been used in traditional medicine for various purposes, such as treating inflammation, pain, and gastrointestinal disorders. However, their use has been linked to severe kidney damage and upper urinary tract urothelial carcinoma (a type of kidney cancer) in humans.

The nephrotoxicity and carcinogenicity of aristolochic acids are believed to be due to their ability to form DNA adducts, which can lead to mutations and chromosomal damage in the kidneys and other organs. As a result, the use of products containing aristolochic acids has been banned or restricted in many countries, and they are considered to be unsafe for human consumption.

Adrenochrome is a chemical compound that is formed when adrenaline (epinephrine) is oxidized. It is not a naturally occurring hormone or neurotransmitter, but rather a byproduct of the breakdown of these substances. The existence of adrenochrome in the human body is controversial and its effects on the human brain are not well understood.

In popular culture, adrenochrome has been associated with theories about its psychoactive properties and alleged use as a drug in illegal or illicit activities. However, there is no scientific evidence to support these claims and they should be regarded with skepticism. The misinformation surrounding adrenochrome may have originated from Hunter S. Thompson's book "Fear and Loathing in Las Vegas," where it was described as a drug that produces intense hallucinations and feelings of euphoria. However, this portrayal is not based on any scientific evidence and should be considered fiction.

Aflatoxin B1 is a toxic metabolite produced by certain strains of the fungus Aspergillus flavus and Aspergillus parasiticus. It is a potent carcinogen and is classified as a Group 1 carcinogen by the International Agency for Research on Cancer (IARC). Aflatoxin B1 contamination can occur in a variety of agricultural products, including grains, nuts, spices, and dried fruits, and is a particular concern in regions with hot and humid climates. Exposure to aflatoxin B1 can occur through the consumption of contaminated food and has been linked to various health effects, including liver cancer, immune suppression, and stunted growth in children.

Aminopyrine N-demethylase is an enzyme that plays a role in the metabolism of drugs and other xenobiotics. It is primarily found in the liver and is responsible for catalyzing the N-demethylation of aminopyrine, a compound with analgesic and anti-inflammatory properties.

The enzyme works by transferring a methyl group from the aminopyrine molecule to a cofactor called NADPH, resulting in the formation of formaldehyde and dimethylaniline as products. This reaction is an important step in the biotransformation of many drugs and other foreign substances, allowing them to be more easily excreted from the body.

Aminopyrine N-demethylase is classified as a cytochrome P450 enzyme, which is a group of heme-containing proteins that are involved in oxidative metabolism. The activity of this enzyme can be influenced by various factors, including genetic polymorphisms, age, sex, and exposure to certain drugs or chemicals.

In addition to its role in drug metabolism, aminopyrine N-demethylase has also been used as a marker of liver function and as a tool for studying the regulation of cytochrome P450 enzymes.

Cytochrome P-450 CYP1A1 is an enzyme that is part of the cytochrome P450 family, which are a group of enzymes involved in the metabolism of drugs and other xenobiotics (foreign substances) in the body. Specifically, CYP1A1 is found primarily in the liver and lungs and plays a role in the metabolism of polycyclic aromatic hydrocarbons (PAHs), which are chemicals found in tobacco smoke and are produced by the burning of fossil fuels and other organic materials.

CYP1A1 also has the ability to activate certain procarcinogens, which are substances that can be converted into cancer-causing agents (carcinogens) within the body. Therefore, variations in the CYP1A1 gene may influence an individual's susceptibility to cancer and other diseases.

The term "P-450" refers to the fact that these enzymes absorb light at a wavelength of 450 nanometers when they are combined with carbon monoxide, giving them a characteristic pink color. The "CYP" stands for "cytochrome P," and the number and letter designations (e.g., 1A1) indicate the specific enzyme within the family.

Carcinogens are agents (substances or mixtures of substances) that can cause cancer. They may be naturally occurring or man-made. Carcinogens can increase the risk of cancer by altering cellular DNA, disrupting cellular function, or promoting cell growth. Examples of carcinogens include certain chemicals found in tobacco smoke, asbestos, UV radiation from the sun, and some viruses.

It's important to note that not all exposures to carcinogens will result in cancer, and the risk typically depends on factors such as the level and duration of exposure, individual genetic susceptibility, and lifestyle choices. The International Agency for Research on Cancer (IARC) classifies carcinogens into different groups based on the strength of evidence linking them to cancer:

Group 1: Carcinogenic to humans
Group 2A: Probably carcinogenic to humans
Group 2B: Possibly carcinogenic to humans
Group 3: Not classifiable as to its carcinogenicity to humans
Group 4: Probably not carcinogenic to humans

This information is based on medical research and may be subject to change as new studies become available. Always consult a healthcare professional for medical advice.

Glutathione is a tripeptide composed of three amino acids: cysteine, glutamic acid, and glycine. It is a vital antioxidant that plays an essential role in maintaining cellular health and function. Glutathione helps protect cells from oxidative stress by neutralizing free radicals, which are unstable molecules that can damage cells and contribute to aging and diseases such as cancer, heart disease, and dementia. It also supports the immune system, detoxifies harmful substances, and regulates various cellular processes, including DNA synthesis and repair.

Glutathione is found in every cell of the body, with particularly high concentrations in the liver, lungs, and eyes. The body can produce its own glutathione, but levels may decline with age, illness, or exposure to toxins. As such, maintaining optimal glutathione levels through diet, supplementation, or other means is essential for overall health and well-being.

DNA adducts are chemical modifications or alterations that occur when DNA molecules become attached to or bound with certain harmful substances, such as toxic chemicals or carcinogens. These attachments can disrupt the normal structure and function of the DNA, potentially leading to mutations, genetic damage, and an increased risk of cancer and other diseases.

DNA adducts are formed when a reactive molecule from a chemical agent binds covalently to a base in the DNA molecule. This process can occur either spontaneously or as a result of exposure to environmental toxins, such as those found in tobacco smoke, certain industrial chemicals, and some medications.

The formation of DNA adducts is often used as a biomarker for exposure to harmful substances, as well as an indicator of potential health risks associated with that exposure. Researchers can measure the levels of specific DNA adducts in biological samples, such as blood or urine, to assess the extent and duration of exposure to certain chemicals or toxins.

It's important to note that not all DNA adducts are necessarily harmful, and some may even play a role in normal cellular processes. However, high levels of certain DNA adducts have been linked to an increased risk of cancer and other diseases, making them a focus of ongoing research and investigation.

Anticarcinogenic agents are substances that prevent, inhibit or reduce the development of cancer. They can be natural or synthetic compounds that interfere with the process of carcinogenesis at various stages, such as initiation, promotion, and progression. Anticarcinogenic agents may work by preventing DNA damage, promoting DNA repair, reducing inflammation, inhibiting cell proliferation, inducing apoptosis (programmed cell death), or modulating immune responses.

Examples of anticarcinogenic agents include chemopreventive agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and retinoids; phytochemicals found in fruits, vegetables, and other plant-based foods; and medications used to treat cancer, such as chemotherapy, radiation therapy, and targeted therapies.

It is important to note that while some anticarcinogenic agents have been shown to be effective in preventing or reducing the risk of certain types of cancer, they may also have potential side effects and risks. Therefore, it is essential to consult with a healthcare professional before using any anticarcinogenic agent for cancer prevention or treatment purposes.

Glucosinolates are naturally occurring compounds found in various plants, particularly in cruciferous vegetables such as broccoli, Brussels sprouts, cabbage, and mustard greens. They are sulfur-containing glucosides that can be hydrolyzed by the enzyme myrosinase when the plant tissue is damaged, leading to the formation of biologically active compounds like isothiocyanates, thiocyanates, and nitriles. These breakdown products have been shown to exhibit various health benefits, such as anti-cancer, anti-inflammatory, and antimicrobial activities. However, excessive intake or exposure may also cause adverse effects in some individuals.

Thiocyanates are chemical compounds that contain the thiocyanate ion (SCN-), which consists of a sulfur atom, a carbon atom, and a nitrogen atom. The thiocyanate ion is formed by the removal of a hydrogen ion from thiocyanic acid (HSCN). Thiocyanates are used in various applications, including pharmaceuticals, agrochemicals, and industrial chemicals. In medicine, thiocyanates have been studied for their potential effects on the thyroid gland and their use as a treatment for cyanide poisoning. However, excessive exposure to thiocyanates can be harmful and may cause symptoms such as irritation of the eyes, skin, and respiratory tract, as well as potential impacts on thyroid function.

The Cytochrome P-450 (CYP450) enzyme system is a group of enzymes found primarily in the liver, but also in other organs such as the intestines, lungs, and skin. These enzymes play a crucial role in the metabolism and biotransformation of various substances, including drugs, environmental toxins, and endogenous compounds like hormones and fatty acids.

The name "Cytochrome P-450" refers to the unique property of these enzymes to bind to carbon monoxide (CO) and form a complex that absorbs light at a wavelength of 450 nm, which can be detected spectrophotometrically.

The CYP450 enzyme system is involved in Phase I metabolism of xenobiotics, where it catalyzes oxidation reactions such as hydroxylation, dealkylation, and epoxidation. These reactions introduce functional groups into the substrate molecule, which can then undergo further modifications by other enzymes during Phase II metabolism.

There are several families and subfamilies of CYP450 enzymes, each with distinct substrate specificities and functions. Some of the most important CYP450 enzymes include:

1. CYP3A4: This is the most abundant CYP450 enzyme in the human liver and is involved in the metabolism of approximately 50% of all drugs. It also metabolizes various endogenous compounds like steroids, bile acids, and vitamin D.
2. CYP2D6: This enzyme is responsible for the metabolism of many psychotropic drugs, including antidepressants, antipsychotics, and beta-blockers. It also metabolizes some endogenous compounds like dopamine and serotonin.
3. CYP2C9: This enzyme plays a significant role in the metabolism of warfarin, phenytoin, and nonsteroidal anti-inflammatory drugs (NSAIDs).
4. CYP2C19: This enzyme is involved in the metabolism of proton pump inhibitors, antidepressants, and clopidogrel.
5. CYP2E1: This enzyme metabolizes various xenobiotics like alcohol, acetaminophen, and carbon tetrachloride, as well as some endogenous compounds like fatty acids and prostaglandins.

Genetic polymorphisms in CYP450 enzymes can significantly affect drug metabolism and response, leading to interindividual variability in drug efficacy and toxicity. Understanding the role of CYP450 enzymes in drug metabolism is crucial for optimizing pharmacotherapy and minimizing adverse effects.

Carboxylesterase is a type of enzyme that catalyzes the hydrolysis of ester bonds in carboxylic acid esters, producing alcohol and carboxylate products. These enzymes are widely distributed in various tissues, including the liver, intestines, and plasma. They play important roles in detoxification, metabolism, and the breakdown of xenobiotics (foreign substances) in the body.

Carboxylesterases can also catalyze the reverse reaction, forming esters from alcohols and carboxylates, which is known as transesterification or esterification. This activity has applications in industrial processes and biotechnology.

There are several families of carboxylesterases, with different substrate specificities, kinetic properties, and tissue distributions. These enzymes have been studied for their potential use in therapeutics, diagnostics, and drug delivery systems.

The liver is a large, solid organ located in the upper right portion of the abdomen, beneath the diaphragm and above the stomach. It plays a vital role in several bodily functions, including:

1. Metabolism: The liver helps to metabolize carbohydrates, fats, and proteins from the food we eat into energy and nutrients that our bodies can use.
2. Detoxification: The liver detoxifies harmful substances in the body by breaking them down into less toxic forms or excreting them through bile.
3. Synthesis: The liver synthesizes important proteins, such as albumin and clotting factors, that are necessary for proper bodily function.
4. Storage: The liver stores glucose, vitamins, and minerals that can be released when the body needs them.
5. Bile production: The liver produces bile, a digestive juice that helps to break down fats in the small intestine.
6. Immune function: The liver plays a role in the immune system by filtering out bacteria and other harmful substances from the blood.

Overall, the liver is an essential organ that plays a critical role in maintaining overall health and well-being.

Cytochrome P-450 CYP1A2 is a specific isoform of the cytochrome P-450 enzyme system, which is involved in the metabolism of various xenobiotics, including drugs and toxins, in the body. This enzyme is primarily located in the endoplasmic reticulum of hepatocytes, or liver cells, and plays a significant role in the oxidative metabolism of certain medications, such as caffeine, theophylline, and some antidepressants.

CYP1A2 is induced by various factors, including smoking, charcoal-grilled foods, and certain medications, which can increase its enzymatic activity and potentially affect the metabolism and clearance of drugs that are substrates for this enzyme. Genetic polymorphisms in the CYP1A2 gene can also lead to differences in enzyme activity among individuals, resulting in variable drug responses and potential adverse effects.

In summary, Cytochrome P-450 CYP1A2 is a liver enzyme involved in the metabolism of various drugs and toxins, with genetic and environmental factors influencing its activity and impacting individual responses to medications.

Isothiocyanates are organic compounds that contain a functional group made up of a carbon atom, a nitrogen atom, and a sulfur atom, with the formula RN=C=S (where R can be an alkyl or aryl group). They are commonly found in cruciferous vegetables such as broccoli, brussels sprouts, and wasabi. Isothiocyanates have been studied for their potential health benefits, including their anticancer and anti-inflammatory properties. However, they can also be toxic in high concentrations.

Enzyme induction is a process by which the activity or expression of an enzyme is increased in response to some stimulus, such as a drug, hormone, or other environmental factor. This can occur through several mechanisms, including increasing the transcription of the enzyme's gene, stabilizing the mRNA that encodes the enzyme, or increasing the translation of the mRNA into protein.

In some cases, enzyme induction can be a beneficial process, such as when it helps the body to metabolize and clear drugs more quickly. However, in other cases, enzyme induction can have negative consequences, such as when it leads to the increased metabolism of important endogenous compounds or the activation of harmful procarcinogens.

Enzyme induction is an important concept in pharmacology and toxicology, as it can affect the efficacy and safety of drugs and other xenobiotics. It is also relevant to the study of drug interactions, as the induction of one enzyme by a drug can lead to altered metabolism and effects of another drug that is metabolized by the same enzyme.

I'm sorry for any confusion, but "pyrazines" is not a term commonly used in medical definitions. Pyrazines are actually a class of organic compounds that contain a ring made up of two nitrogen atoms and three carbon atoms. They are found in various foods and contribute to their flavors. If you have any questions about organic chemistry or food science, I'd be happy to try to help!

Carboxylic ester hydrolases are a class of enzymes that catalyze the hydrolysis of ester bonds in carboxylic acid esters, producing alcohols and carboxylates. This group includes several subclasses of enzymes such as esterases, lipases, and thioesterases. These enzymes play important roles in various biological processes, including metabolism, detoxification, and signal transduction. They are widely used in industrial applications, such as the production of biodiesel, pharmaceuticals, and food ingredients.

Microsomes, liver refers to a subcellular fraction of liver cells (hepatocytes) that are obtained during tissue homogenization and subsequent centrifugation. These microsomal fractions are rich in membranous structures known as the endoplasmic reticulum (ER), particularly the rough ER. They are involved in various important cellular processes, most notably the metabolism of xenobiotics (foreign substances) including drugs, toxins, and carcinogens.

The liver microsomes contain a variety of enzymes, such as cytochrome P450 monooxygenases, that are crucial for phase I drug metabolism. These enzymes help in the oxidation, reduction, or hydrolysis of xenobiotics, making them more water-soluble and facilitating their excretion from the body. Additionally, liver microsomes also host other enzymes involved in phase II conjugation reactions, where the metabolites from phase I are further modified by adding polar molecules like glucuronic acid, sulfate, or acetyl groups.

In summary, liver microsomes are a subcellular fraction of liver cells that play a significant role in the metabolism and detoxification of xenobiotics, contributing to the overall protection and maintenance of cellular homeostasis within the body.

Oxidation-Reduction (redox) reactions are a type of chemical reaction involving a transfer of electrons between two species. The substance that loses electrons in the reaction is oxidized, and the substance that gains electrons is reduced. Oxidation and reduction always occur together in a redox reaction, hence the term "oxidation-reduction."

In biological systems, redox reactions play a crucial role in many cellular processes, including energy production, metabolism, and signaling. The transfer of electrons in these reactions is often facilitated by specialized molecules called electron carriers, such as nicotinamide adenine dinucleotide (NAD+/NADH) and flavin adenine dinucleotide (FAD/FADH2).

The oxidation state of an element in a compound is a measure of the number of electrons that have been gained or lost relative to its neutral state. In redox reactions, the oxidation state of one or more elements changes as they gain or lose electrons. The substance that is oxidized has a higher oxidation state, while the substance that is reduced has a lower oxidation state.

Overall, oxidation-reduction reactions are fundamental to the functioning of living organisms and are involved in many important biological processes.

Isoenzymes, also known as isoforms, are multiple forms of an enzyme that catalyze the same chemical reaction but differ in their amino acid sequence, structure, and/or kinetic properties. They are encoded by different genes or alternative splicing of the same gene. Isoenzymes can be found in various tissues and organs, and they play a crucial role in biological processes such as metabolism, detoxification, and cell signaling. Measurement of isoenzyme levels in body fluids (such as blood) can provide valuable diagnostic information for certain medical conditions, including tissue damage, inflammation, and various diseases.

High-performance liquid chromatography (HPLC) is a type of chromatography that separates and analyzes compounds based on their interactions with a stationary phase and a mobile phase under high pressure. The mobile phase, which can be a gas or liquid, carries the sample mixture through a column containing the stationary phase.

In HPLC, the mobile phase is a liquid, and it is pumped through the column at high pressures (up to several hundred atmospheres) to achieve faster separation times and better resolution than other types of liquid chromatography. The stationary phase can be a solid or a liquid supported on a solid, and it interacts differently with each component in the sample mixture, causing them to separate as they travel through the column.

HPLC is widely used in analytical chemistry, pharmaceuticals, biotechnology, and other fields to separate, identify, and quantify compounds present in complex mixtures. It can be used to analyze a wide range of substances, including drugs, hormones, vitamins, pigments, flavors, and pollutants. HPLC is also used in the preparation of pure samples for further study or use.

F344 is a strain code used to designate an outbred stock of rats that has been inbreeded for over 100 generations. The F344 rats, also known as Fischer 344 rats, were originally developed at the National Institutes of Health (NIH) and are now widely used in biomedical research due to their consistent and reliable genetic background.

Inbred strains, like the F344, are created by mating genetically identical individuals (siblings or parents and offspring) for many generations until a state of complete homozygosity is reached, meaning that all members of the strain have identical genomes. This genetic uniformity makes inbred strains ideal for use in studies where consistent and reproducible results are important.

F344 rats are known for their longevity, with a median lifespan of around 27-31 months, making them useful for aging research. They also have a relatively low incidence of spontaneous tumors compared to other rat strains. However, they may be more susceptible to certain types of cancer and other diseases due to their inbred status.

It's important to note that while F344 rats are often used as a standard laboratory rat strain, there can still be some genetic variation between individual animals within the same strain, particularly if they come from different suppliers or breeding colonies. Therefore, it's always important to consider the source and history of any animal model when designing experiments and interpreting results.

Substrate specificity in the context of medical biochemistry and enzymology refers to the ability of an enzyme to selectively bind and catalyze a chemical reaction with a particular substrate (or a group of similar substrates) while discriminating against other molecules that are not substrates. This specificity arises from the three-dimensional structure of the enzyme, which has evolved to match the shape, charge distribution, and functional groups of its physiological substrate(s).

Substrate specificity is a fundamental property of enzymes that enables them to carry out highly selective chemical transformations in the complex cellular environment. The active site of an enzyme, where the catalysis takes place, has a unique conformation that complements the shape and charge distribution of its substrate(s). This ensures efficient recognition, binding, and conversion of the substrate into the desired product while minimizing unwanted side reactions with other molecules.

Substrate specificity can be categorized as:

1. Absolute specificity: An enzyme that can only act on a single substrate or a very narrow group of structurally related substrates, showing no activity towards any other molecule.
2. Group specificity: An enzyme that prefers to act on a particular functional group or class of compounds but can still accommodate minor structural variations within the substrate.
3. Broad or promiscuous specificity: An enzyme that can act on a wide range of structurally diverse substrates, albeit with varying catalytic efficiencies.

Understanding substrate specificity is crucial for elucidating enzymatic mechanisms, designing drugs that target specific enzymes or pathways, and developing biotechnological applications that rely on the controlled manipulation of enzyme activities.

In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."

1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.

2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.

3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.

4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).

Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.

Sprague-Dawley rats are a strain of albino laboratory rats that are widely used in scientific research. They were first developed by researchers H.H. Sprague and R.C. Dawley in the early 20th century, and have since become one of the most commonly used rat strains in biomedical research due to their relatively large size, ease of handling, and consistent genetic background.

Sprague-Dawley rats are outbred, which means that they are genetically diverse and do not suffer from the same limitations as inbred strains, which can have reduced fertility and increased susceptibility to certain diseases. They are also characterized by their docile nature and low levels of aggression, making them easier to handle and study than some other rat strains.

These rats are used in a wide variety of research areas, including toxicology, pharmacology, nutrition, cancer, and behavioral studies. Because they are genetically diverse, Sprague-Dawley rats can be used to model a range of human diseases and conditions, making them an important tool in the development of new drugs and therapies.

... detoxication by inducible cytochrome P450 is more important than metabolic activation". Molecular Pharmacology. 65 (5): 1225-37 ... Ma Q, Lu AY (Jul 2007). "CYP1A induction and human risk assessment: an evolving tale of in vitro and in vivo studies". Drug ... He J, Wang C, Zhu Y, Ai D (Dec 2015). "Soluble epoxide hydrolase: A potential target for metabolic diseases". Journal of ... CYP1A1 is involved in phase I xenobiotic and drug metabolism (one substrate of it is theophylline). It is inhibited by ...
... detoxication by inducible cytochrome P450 is more important than metabolic activation". Molecular Pharmacology. 65 (5): 1225-37 ... Beresford, AP (1993). "CYP1A1: friend or foe?". Drug Metab Rev. 25 (4): 503-17. doi:10.3109/03602539308993984. PMID 8313840. ...
... metabolic detoxication, drug MeSH G12.091.690.140.600.500 - metabolic detoxication, phase i MeSH G12.091.690.140.600.750 - ... drug antagonism MeSH G12.361.477 - drug synergism MeSH G12.361.511 - food-drug interactions MeSH G12.361.755 - herb-drug ... drug resistance, fungal MeSH G12.392.269.383.500 - drug resistance, multiple, fungal MeSH G12.392.269.420 - drug resistance, ... drug resistance, multiple, fungal MeSH G12.392.300.750 - drug resistance, multiple, viral MeSH G12.392.395 - drug resistance, ...
... metabolic detoxication, drug MeSH G06.535.780.202.820.500 - metabolic detoxication, phase i MeSH G06.535.780.202.820.750 - ... metabolic detoxication, phase ii MeSH G06.535.780.559 - therapeutic equivalency MeSH G06.535.780.917 - tissue distribution MeSH ...
... is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More ... This field became defined as a separate area of study with the publication by Richard Williams of the book Detoxication ... Mizuno N, Niwa T, Yotsumoto Y, Sugiyama Y (September 2003). "Impact of drug transporter studies on drug discovery and ... For example, the rate of metabolism determines the duration and intensity of a drug's pharmacologic action. Drug metabolism ...
Local anesthetic receptor site binds local anesthetics, antiarrhythmic drugs and antiepileptic drugs NSTX and other site 1 ... García C, Barriga A, Díaz JC, Lagos M, Lagos N (January 2010). "Paralytic Route of metabolization and detoxication of ... Some evidence suggest the presence of metabolic pathways for the sequential oxidation and glucuronidation of PST in vitro, both ... accessed: May 6, 2012)[11] U.S. Food and Drug Administration. Fish and Fishery Products Hazards and Controls Guidance, Fourth ...
The ability of one P450 substrate to affect the concentrations of another in this manner is the basis for so-called drug-drug ... Glucose induction of bile acid synthesis have an important implication in metabolic control of glucose, lipid, and energy ... Metabolism of foreign chemicals frequently results in successful detoxication of the irritant; However, the actions of P450 ... In the early 1960s, P450 was thought to be one enzyme, and by the mid 1960s it was associated with drug and steroid metabolism ...
"Lisdexamfetamine - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022. Drugs of Abuse (PDF). Drug Enforcement ... The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation, N-oxidation, N- ... role in bioactivation and detoxication". Journal of Pharmacology and Experimental Therapeutics. 288 (3): 1251-1260. PMID ... Drugs with non-standard legal status, Multiple chemicals in Infobox drug, Chemicals using indexlabels, Drug has EMA link, ...
These processes are particularly well-studied as part of drug metabolism, as they influence the pharmacokinetics of a drug in ... xenobiotic metabolic process (2013-04-13). "AmiGO: xenobiotic metabolic process Details". Amigo.geneontology.org. Archived from ... Detoxification or detoxication (detox for short) is the physiological or medicinal removal of toxic substances from a living ... Detoxification may be achieved drug-free or may use medications as an aspect of treatment. Often drug detoxification and ...
The metabolic and clinical manifestations of TMAU are generally regarded as benign, as there is no associated organ dysfunction ... Schmidt AC, Leroux JC (2020). "Treatments of trimethylaminuria: where we are and where we might be heading". Drug Discov Today ... 1998). "Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication". Human ... Trimethylaminuria (TMAU), also known as fish odor syndrome or fish malodor syndrome, is a rare metabolic disorder that causes a ...
Table 5: N-containing drugs and xenobiotics oxygenated by FMO Cashman JR, Xiong YN, Xu L, Janowsky A (March 1999). "N- ... In species where aromatic hydroxylation of amphetamine is the major metabolic pathway, p-hydroxyamphetamine (POH) and p- ... role in bioactivation and detoxication". Journal of Pharmacology and Experimental Therapeutics. 288 (3): 1251-1260. PMID ... The percent of the drug hydroxylated to hydroxynorephedrine was comparable in all subjects (6.5-9.62) (Table 3). Freeman JJ, ...
Infobox drug with local INN variant, Drugs not assigned an ATC code, Drugs with non-standard legal status, ECHA InfoCard ID ... In species where aromatic hydroxylation of amphetamine is the major metabolic pathway, p-hydroxyamphetamine (POH) and p- ... role in bioactivation and detoxication". Journal of Pharmacology and Experimental Therapeutics. 288 (3): 1251-1260. PMID ... If it is intended as an immediate follow up to another mydriatic drug (cocaine or apraclonidine), then the patient must wait ...
"Drugs Banned In India". Dte.GHS, Ministry of Health and Family Welfare, Government of India. Central Drugs Standard Control ... In species where aromatic hydroxylation of amphetamine is the major metabolic pathway, p-hydroxyamphetamine (POH) and p- ... role in bioactivation and detoxication". Journal of Pharmacology and Experimental Therapeutics. 288 (3): 1251-1260. PMID ... In the United States, the Food and Drug Administration (FDA) issued a public health advisory against the use of the drug in ...
Due to illicit drug labs using phenylacetone to make amphetamines, phenylacetone was declared a schedule II controlled ... In species where aromatic hydroxylation of amphetamine is the major metabolic pathway, p-hydroxyamphetamine (POH) and p- ... Role in Bioactivation and Detoxication". Journal of Pharmacology and Experimental Therapeutics. 288 (3): 1251-1260. ISSN 0022- ... Drug Enforcement Administration. 11 February 1980. Archived (PDF) from the original on 3 March 2022. Retrieved 16 January 2023 ...
Drugs missing an ATC code, Drugs with no legal status, Articles containing unverified chemical infoboxes, Amphetamine, ... In species where aromatic hydroxylation of amphetamine is the major metabolic pathway, p-hydroxyamphetamine (POH) and p- ... role in bioactivation and detoxication". Journal of Pharmacology and Experimental Therapeutics. 288 (3): 1251-1260. PMID ... Table 5: N-containing drugs and xenobiotics oxygenated by FMO Cashman JR, Xiong YN, Xu L, Janowsky A (March 1999). "N- ...
The known metabolic pathways include: Methamphetamine and amphetamine are often measured in urine or blood as part of a drug ... role in bioactivation and detoxication". J. Pharmacol. Exp. Ther. 288 (3): 1251-1260. PMID 10027866. "Chemical and Physical ... cite encyclopedia}}: ,work= ignored (help) "Methamphetamine". Drug profiles. European Monitoring Centre for Drugs and Drug ... The latter is no longer produced and is a extended-release form of the drug, flattening the curve of the effect of the drug ...
N-containing drugs and xenobiotics oxygenated by FMO Table 6: S-containing drugs and xenobiotics oxygenated by FMO Table 7: FMO ... 1998). "Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication". Hum. ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to ... substrate specificity and role in drug metabolism". Curr. Drug Metab. 1 (2): 181-191. doi:10.2174/1389200003339135. PMID ...
Roy Jensen in 1976 theorised that primordial enzymes had to be highly promiscuous in order for metabolic networks to assemble ... Jakoby WB, Ziegler DM (December 1990). "The enzymes of detoxication". The Journal of Biological Chemistry. 265 (34): 20715-8. ... drug binding and subsequent reaction is a promiscuous activity as the enzyme catalyses an inactivating reaction towards a novel ... As a consequence, many central-metabolic enzymes have structural homologues that diverged before the last universal common ...
"Drugs@FDA: Dexedrine". U.S. Food and Drug Administration (FDA). Retrieved 28 March 2022. "Drugs@FDA: Dexedrine". U.S. Food and ... The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation, N-oxidation, N- ... role in bioactivation and detoxication". Journal of Pharmacology and Experimental Therapeutics. 288 (3): 1251-1260. PMID ... Drugs acting on the cardiovascular system, Drugs acting on the nervous system, Enantiopure drugs, Ergogenic aids, Euphoriants, ...
"National Drug Code Amphetamine Search Results". National Drug Code Directory. United States Food and Drug Administration. ... The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation, N-oxidation, N- ... role in bioactivation and detoxication". Journal of Pharmacology and Experimental Therapeutics. 288 (3): 1251-1260. PMID ... Combination drugs, Drugs acting on the cardiovascular system, Drugs acting on the nervous system, Ergogenic aids, Euphoriants, ...
... and predict metabolic stability as well as drug-drug interactions. Additionally, HepaRG has been used to evaluate acute and ... and Detoxication". Toxicological Sciences. 147 (2): 412-424. doi:10.1093/toxsci/kfv136. PMC 4583060. PMID 26160117. Tolosa, ... The high reproducibility of the drug-induced metabolic enzyme levels between batches enables routine high-throughput analysis ... "Comparison of Cryopreserved HepaRG Cells with Cryopreserved Human Hepatocytes for Prediction of Clearance for 26 Drugs". Drug ...
European Monitoring Centre for Drugs and Drug Addiction. Retrieved 5 February 2019. European Monitoring Centre for Drugs Drug ... The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation, N-oxidation, N- ... role in bioactivation and detoxication". Journal of Pharmacology and Experimental Therapeutics. 288 (3): 1251-1260. PMID ... "National Drug Code Amphetamine Search Results". National Drug Code Directory. United States Food and Drug Administration. ...
  • Genetic polymorphism of drug metabolism enzymes (GSTM1, GSTT1 and GSTP1) in the healthy Malian population. (harvard.edu)
  • CYP1A1 is involved in phase I xenobiotic and drug metabolism (one substrate of it is theophylline). (wikipedia.org)
  • Xenobiotic metabolism is the set of metabolic pathways that chemically modify xenobiotics , which are compounds foreign to an organism's normal biochemistry, such as drugs and poisons. (bionity.com)
  • The reactions in these pathways are of particular interest in medicine as part of drug metabolism and as a factor contributing to multidrug resistance in infectious diseases and cancer chemotherapy . (bionity.com)
  • The actions of some drugs as substrates or inhibitors of enzymes involved in xenobiotic metabolism are a common reason for hazardous drug interactions . (bionity.com)
  • It has numerous functions e.g. manufacture and secretion of bile, maintenance of blood sugar level, regulation of protein and fat metabolism, formation of ketone bodies and plasma proteins, detoxication, Erythropoiesis etc. (harshulayurpharma.com)
  • Termination of drug metabolism. (inhn.org)
  • Furthermore, PON1 participates in metabolism of some drugs which contain lactone and cyclic carbonates. (biochemia-medica.com)
  • Resvero-SE Active is designed to support the immune system, the gastrointestinal system, and metabolic pathways with a concentrated source of resveratrol. (apexenergetics.com)
  • Taking lots of vitamins and supplements without addressing and supporting the main detoxication pathways is often overlooked. (drkaslow.com)
  • A couple of years later Bernard Brodie and his associates revealed that the main pathways used by the organism for metabolizing drugs are: (1) oxidation by microsomal enzymes in the liver, (2) other oxidative reactions, such as dehydrogenation, oxidative deamination, (3) reduction reactions, (4) O-methylation, (5) hydrolysis (of esters and amides) and (6) conjugation (Brodie, Axelrod, Cooper et al. (inhn.org)
  • The transcription factor networks that regulate basal and xenobiotic-modulated expression of the hepatic sulfotransferases affect the dynamics of xenobiotic detoxication, carcinogen bioactivation and metabolic homeostasis. (eurekaselect.com)
  • Everyone is constantly being exposed to environmental, microbial, and metabolic toxins even if they "eat organic" and drink "purified water" and so on. (drkaslow.com)
  • nutrients are converted to their useable forms, what is redundant gets separated for elimination, and toxins - both, those originated externally, and those created during the metabolic process - have to be either neutralized, or safely eliminated. (healthknot.com)
  • These findings boost the design that seizures are the cause of the immune and inflamma- tory disorders observed in patients with drug-resistant epilepsy. (daubnet.com)
  • Liver carcinogenesis is a multistep, long process associated with multiple risk factors, e.g. viral hepatitis, alcohol abuse, metabolic disorders, and obesity [ 2 ]. (aging-us.com)
  • 2 FMOs are involved in the pathogenic process of trimethylaminuria, atherosclerosis, cardiovascular disease, diabetes, and metabolic disorders. (xiahepublishing.com)
  • Hence, we investigated whether other factors considered as potential causes of BEN [a mycotoxin ochratoxin A (OTA), Cd, Pb, Se and As ions and organic compounds (i.e. phthalates) released from lignite deposits in BEN areas] can influence detoxication of AAI, whose concentrations are crucial for BEN development. (nel.edu)
  • Relevant of mutagenicity and clastogenici- angiosarcomas of the liver, which carcinogens discussed in this chap- ty, including the induction of sister are rare tumours, were identified in ter do not include pharmaceutical chromatid exchange (SCE), chro- humans, rats, and mice exposed to drugs classified in Group 1, which mosomal aberrations (CA), and mi- vinyl chloride. (who.int)
  • It prevents the drugs from being metabolized or oxidized when they first pass through the liver. (curejoy.com)
  • Where drug pharmacokinetics becomes an important factor, this statement has potential implications for sensitization of cyst cells in vivo. (hdacassay.com)
  • The psychomotor stimulant cocaine is inactivated primarily by hydrolysis to benzoylecgonine, the major urinary metabolite of the drug. (inra.fr)
  • The enzymatic activity suggests that it may play an important role in regulating the detoxication of cocaine and in the formation of the active metabolite cocaethylene. (inra.fr)
  • It speeds up the absorption of drugs from the gastrointestinal tract and reduces the time it takes to travel through the tract. (curejoy.com)
  • To overcome these detractions and develop an improved tier 1 screening system that reduces the cost and time required for new compound evaluation, 490 BioTech proposes to develop a panel of multiple continuously bioluminescent human cell lines that will permit the simultaneous monitoring of each line to ascertain both the individual effects of compound treatment as well as the downstream effects of a compound's biotransformed metabolic breakdown products in real-time. (inknowvation.com)
  • en] In vitro repeated dose testing for the assessment of chronic drug-induced effects is a huge challenge in preclinical pharmaceutical drug development. (uni.lu)
  • The drug has anti-inflammatory, antispasmodic and sedative effects. (altmeyers.org)
  • The results show low effects of BBP, cadmium and selenium ions, and/or their combinations on AAI detoxication. (nel.edu)
  • Since our resources are somewhat limited, we need indigenous medicines free from undesirable side effects and using simpler technologies than that being utilized by the multinational drug industry, to serve our needs in the field of human health-care. (harshulayurpharma.com)
  • Adaptocrine is formulated to counter the metabolic effects of temporary stress and support the body when energetically spent. (apexenergetics.com)
  • In this study, we maintained primary human hepatocytes in a serum-free cultivation medium for more than 3 weeks and analyzed physiology, viability and drug metabolizing capacities of the hepatocytes. (uni.lu)
  • Chronic toxicity results in discontinuation of therapy or post-marketing withdrawal of drugs despite in vivo preclinical screening. (uni.lu)
  • In fact, benzoylecgonine can last in the body for a very long time (a few days) and, thus, is responsible for the long-term toxicity of cocaine and a commonly used marker for drug addiction diagnosis in pre-employment drug tests. (inra.fr)
  • Because of this toxicity, the removal of even minute amounts is essential for safe parenteral administration of drugs and also for septic shock patients' care. (fh-aachen.de)
  • Forget about hazardous, dangerous drugs and enjoy nature's calming influence instead. (nuubuofficial.com)
  • Trimethylaminuria is a currently confirmed rare inherited metabolic disorder associated with abnormal amounts of dietary-derived trimethylamine and is caused by the mutations in FMO3. (xiahepublishing.com)
  • The drug discovery process requires that upwards of 10,000 molecules be screened for each new lead compound developed and relies upon an expensive and time consuming combination of in vitro cell culture-based and in vivo whole animal-based models to identify, validate, and ensure the safety of any resulting potential therapeutic agents. (inknowvation.com)
  • In contrast, OTA might influence this process, by inhibition of AAI detoxication. (nel.edu)
  • So it is assumed that the native activity of PON1 may be lactonase activity and that physiological substrate may be some lactones which are consumed as food ingredients, drug metabolites (statins, spironolactone and glucocorticoid γ-lactones) and derivatives of fatty acid oxidation process such as 5-hydroxy6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HETE) lactone that resides in HDL (13). (biochemia-medica.com)
  • These include affecting structure and function of organs and cells, changing metabolic functions, raising body temperature, triggering the coagulation cascade, modifying hemodynamics and causing septic shock. (fh-aachen.de)
  • Cytochrome P450-dependent alpha-hydroxylation, followed by sulfonation, represents a metabolic activation pathway, producing products capable of covalent DNA adduction. (oregonstate.edu)
  • With an average of 10,000 novel molecules that must be screened for each new lead compound developed, and an average of 10 to 15 years of research and development at a cost of up to $1B to manufacture one new drug, pharmaceutical companies must develop new testing regimens that provide more data at a lower cost in order to achieve the economics necessary to remain profitable. (inknowvation.com)
  • Bioavailability is the rate at which a drug is absorbed by the body and successfully reaches the target tissue. (curejoy.com)
  • Pharmacodynamic properties are responsible for the differential effect of a psychotropic drug in different psychiatric diagnoses, whereas pharmacokinetic properties for the differential effect of the same drug within a particular diagnosis. (inhn.org)
  • Additionally, the tumour suppressor p53 has been shown to impact CYP1A1 expression thereby modulating the metabolic activation of several environmental carcinogens such as PAHs. (wikipedia.org)
  • It is involved in the metabolic activation of aromatic hydrocarbons (polycyclic aromatic hydrocarbons, PAH), for example, benzo[a]pyrene (BaP), by transforming it to an epoxide. (wikipedia.org)
  • The risk:benefit depends on the rate of metabolic activation versus detoxication. (oregonstate.edu)
  • Mechanistic knowledge is also useful in forming the basis for therapy and the design of new drugs for treatment of human disease. (cloudaccess.net)
  • Oxidative detoxication of carcinogenic 2-nitroanisole by human, rat and rabbit cytochrome P450. (nel.edu)
  • With current in vitro screening assays now representing a $1.4B market with a predicted 12% annual growth rate, we believe we possess a product capable of significantly impacting the chemical/drug screening market and, here in particular, advancing our understanding of cytotoxic chemical biotransformations as they pertain to public health and consumer safety. (inknowvation.com)
  • This graph shows the total number of publications written about "Metabolic Detoxication, Phase II" by people in Harvard Catalyst Profiles by year, and whether "Metabolic Detoxication, Phase II" was a major or minor topic of these publication. (harvard.edu)
  • While there is no end to the hype of these "magic" cures, lets evaluate the real science of the detoxication claim. (chooseanamazinglife.com)
  • Moody JC, Trait AC, Todrick A. Plasma levels of imipramine and desmethylimipramine during drug therapy. (inhn.org)
  • It is implies that the use of the nanosorbents for the attachment of the probiotical microorganisms are highly perspective for decision the important problems, such as the probiotical preparations delivery to the right address and their attachment to intestines mucosa with the following detoxication of gastro-intestinal tract and the normalization of it's microecology. (fh-aachen.de)
  • Below are the most recent publications written about "Metabolic Detoxication, Phase II" by people in Profiles. (harvard.edu)
  • The respectable one, he says, is the medical treatment of people with life-threatening drug addictions. (chooseanamazinglife.com)
  • The usage of vector modified hematopoietic stem cell therapy by which myelocytotoxic and IS drugs are given to the host to create space in the bone marrow for the homing and development of gene adjusted cells will not be examined. (hdacassay.com)
  • Nutrients or drugs are not effective if they aren't absorbed completely. (curejoy.com)
  • Mortal Institutes of Health discount 100mg kamagra mastercard most effective erectile dysfunction drugs. (wgc2010.sk)
  • Cocaine is one of the most addictive drugs without a U.S. Food and Drug Administration (FDA)-approved medication. (inra.fr)
  • In other cases, however, the added sulfuryl may change a relatively harmless molecule into a powerful carcinogen, or in the case of minoxidil, may convert a neutral molecule into an active drug. (rcsb.org)
  • Metabolic Detoxication, Phase II" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (harvard.edu)
  • Dr. Ward was perceived as a skeptic about alternative medicine because she had written a negative paper on Andrew Ivy, M.D., proponent of the unconventional drug Krebiozen, who had once been president of her medical school. (gerson-research.org)