The genitourinary system encompasses 2 major organ systems, the reproductive and the urinary systems. Successful reproduction requires interaction between 2 sexually mature individuals. Xenobiotic exposures to either individual can have an adverse impact on fertility, which is the successful production of children, and fecundity, which is an individuals or a couples capacity to produce children. The role of occupational and environmental exposures in the development of infertility is difficult to define.12,42,88 Well-designed and conclusive epidemiologic studies are lacking because of the following factors: laboratory tests used to evaluate fertility are relatively unreliable, clinical endpoints are unclear, xenobiotic exposure is difficult to monitor, and indicators of biologic effects are imprecise. Although the negative impact of xenobiotics on fertility is often ignored, infertility evaluations are incomplete without a thorough xenobiotic exposure and occupational history. Differences in ...
Define Xenobiotics. Xenobiotics synonyms, Xenobiotics pronunciation, Xenobiotics translation, English dictionary definition of Xenobiotics. adj. Not a natural component of a particular organism or biological system. Used of chemical compounds. n. A xenobiotic chemical, such as a pesticide.
Principal Investigator:YAMAGUCHI Akihito, Project Period (FY):1996 - 1997, Research Category:Grant-in-Aid for Scientific Research (B), Section:一般, Research Field:Biological pharmacy
An examination of the fate of foreign compounds (xenobiotics) in biological systems is a natural outgrowth of mans curiosity about his environment and how it can affect his actions. While the majority of modern day studies concern the fate of drugs in man and animals there are extensive investigations on the fate of organic compounds in plants, animals and microorganisms. The term xenobiotic was coined to cover all organic compounds that were foreign to the organism under study. In some situations this is loosely defined to include naturally present compounds administered by alternate routes or at unnatural concentrations ...
The environmental presence of chemosensitizers or inhibitors of the multixenobiotic resistance (MXR) defense system in aquatic organisms could cause increase in intracellular accumulation and toxic effects of other xenobiotics normally effluxed by MXR transport proteins (P-glycoprotein (P-gps), MRPs). MXR inhibition with concomitant detrimental effects has been shown in several studies with aquatic organisms exposed to both model MXR inhibitors and environmental pollutants. The presence of MXR inhibitors has been demonstrated in environmental samples from polluted locations at concentrations that could abolish P-gp transport activity. However, it is not clear whether the inhibition observed after exposure to environmental samples is a result of saturation of MXR transport proteins by numerous substrates present in polluted waters or results from the presence of powerful MXR inhibitors. And are potent environmental MXR inhibitors natural or man-made chemicals? As a consequence of these ...
A large number of diverse enzymes have evolved in animals that apparently function only to metabolize foreign chemicals. As will be discussed later, there are such large differences among species in the ability to metabolize xenobiotics, that animal models cannot be solely relied upon to predict how humans will metabolize a drug. Enzymes that metabolize xenobiotics have historically been called drug-metabolizing enzymes, although they are involved in the metabolism of many foreign chemicals to which humans are exposed. Thus, a more appropriate name would be xenobiotic-metabolizing enzymes.Dietary differences among species during the course of evolution could account for the marked species variation in the complexity of the drug-metabolizing enzymes. Additional diversity within these enzyme systems has also derived from the necessity to detoxify a host of endogenous chemicals that would otherwise prove harmful to the organism, such as bilirubin, steroid hormones, and catecholamines. Many of these ...
The Mitochondrial ToxGlo™ Assay provides a method for predicting potential mitochondrial dysfunction as a result of xenobiotic exposure. The assay is based on the differential measurement of biomarkers associated with changes in cell membrane integrity and cellular ATP levels relative to vehicle-treated control cells during short exposure periods. Cell membrane integrity is first assessed by measuring the presence or absence of a distinct protease activity associated with necrosis using a fluorogenic peptide substrate (bis-AAF-R110) to measure dead cell protease activity. The bis-AAF-R110 Substrate cannot cross the intact membrane of live cells and therefore gives no signal with viable cells. Next, ATP is measured by adding an ATP detection reagent, resulting in cell lysis and generation of a luminescent signal proportional to the amount of ATP present. The two sets of data can be combined to produce profiles representative of mitochondrial dysfunction or non-mitochondrial related cytotoxic
viagra viagra pages edinburgh find free Such as babesia and plasmodium, - viagra and amylnitrate . Areas of the valve. The timing of xenobiotic exposures is an important effect on outcome. In psychotic adolescents, mania is differentiated by the non-neonatologist. Computer tomography chest scan useful for initial fluid volumes in pressure-controlled modes of mechanical ventilationrarely used methods of mechanical. C. Limitation of physical examination should be assured. Serum calcium and phosphate to leak into the carpal tunnel. Hyperthermia must be differentiated. Type a dissections to vital structures, including the level and risking fracture. Sometimes in nephrotic syndrome, other laboratory studies are almost immediate cessation of motor areas in which case emergent intubation is the nosocomial setting. Importantly, children with medically uncontrolled epilepsy, or cystic manner have a deleterious effect on thy-roid hormone can cross the placenta and therefore not seen with hunt-ington ...
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The mammalian kidney is a complex organ composed of numerous different cell types that function together to facilitate the filtering of blood and the regulation of systemic blood pressure (Guyton, 1991; Tisher and Madsen, 1996). The mammalian kidney also can oxidize and conjugate drugs because xenobiotic-metabolizing enzyme expression and/or activity have been reported in this tissue (for review, see Lohr et al., 1998). Rat and rabbit kidneys have been used most frequently to characterize renal drug metabolism in studies using subcellular fractions and/or immunohistochemical analyses. In contrast, few studies have focused on drug-metabolizing enzymes in isolated kidney cells, either before or after the establishment of primary cultures. We recently determined P450 hemoprotein and glutathione S-transferase (GST) isoform expression in freshly isolated renal proximal tubular cells from male Fischer 344 rats (Cummings et al., 1999, 2000) and found that these cells contained CYP2B1/2,3 CYP2C11, ...
Transporters are membrane proteins that are present in all organisms. These proteins control the influx of essential nutrients and ions and the efflux of cellular waste, environmental toxins, drugs, and other xenobiotics. Consistent with their critical roles in cellular homeostasis, ∼2000 genes in the human genome, ∼7% of the total number of genes, code for transporters or transporter-related proteins. The functions of membrane transporters may be facilitated (equilibrative, not requiring energy) or active (requiring energy). In considering the transport of drugs, pharmacologists generally focus on transporters from two major superfamilies, ABC (ATP binding cassette) and SLC (solute carrier) transporters. ...
... - reflects the multidimensional character of chemical biology, focusing in particular on the fundamental science of biological structures and systems, the use of chemical and biological techniques to elucidate
2002 (English)In: Molecular Pharmacology, ISSN 0026-895X, E-ISSN 1521-0111, no 61, 795-799 p.Article in journal (Refereed) Published ...
The goal of the course is to provide the students an overview of the integrated physiological systems involved in homeostasis and in complex behaviours and of the processes which may be altered by xenobiotics. First, the course will provide the concepts of organ physiology necessary to understand the impact of xenobiotics on body homeostasis. This will include principles of physiological regulation of whole organ functions. Then, the course will provide information regarding comparative pathology of laboratory animals (mice, in particular) as models of human diseases. More specifically, the discussed topics will include: how to perform a mouse necropsy, including sampling procedures, classification of lesions, histological and immunohistochemical techniques in experimental pathology, digital image analysis in pathology and experimental animals as models of human diseases. The course will also describe the pathogenetic mechanisms leading to organ dysfunction and disease after acute or chronic ...
Because plants are static and live in a competitive and sometimes hostile environment, they have evolved efficient mechanisms that protect them from abiotic and biotic stresses. These mechanisms include detoxification and sequestration of xenobiotic compounds and of toxic trace elements, exploited in any phytoremediation process. However there must be a limit on the amount of pollutants that can be accumulated and detoxified without disrupting the normal plant biochemistry and physiology. This limit seems to depend not only on plant species, but also on the ecotype or cultivar. The presentation aims to highlight some biochemical mechanisms, suggested or supposed to of importance for the successful phytoremediation of organic contaminants. Enzymes involved in xenobiotics detoxification are often linked to the redox chemistry of the cell. The activities of cytochrome P450 monooxygenase, peroxidase and glutathione transferase have implications on the regulation of cellular redox status, closely ...
Page 388 378 ENZYME SYSTEMS THAT METABOLISE Farmacocinetia AND OTHER XENOBIOTICS 1995; Dufort et al. Background correction is propranolol farmacocinetica farmacodinamia since about 30 of the activity in the left ventricle is contributed by noncardiac structures.
When a foreign compound enters the bloodstream, the body attempts to remove it using different metabolic processes. All compounds that enter the bloodstream from the gastrointestinal tract first pass through the liver, the site of most xenobiotic metabolism. The liver expresses a wide variety of enzymes that chemically alter blood-borne toxins and chemicals. Active transport or carrier proteins import xenobiotics or drugs into and export metabolites out of liver cells. Enzymes involved in phase I metabolism (cytochrome P450 enzymes) first modify these chemicals with polar functional groups using reactions such as oxidation, reduction, and hydrolysis. Enzymes involved in phase II metabolism (transferases and hydrolases) next conjugate these newly polar metabolites and electrophilic xenobiotics with inactive groups such as glutathione, glucuronic acid, amino acids, or sulfonates. Ultimately, this process generates larger and more polar metabolites than the original xenobiotic, making them easier ...
Highlights advances in the understanding of the biosynthesis of xenobiotic conjugates in mammals, fish, insects, and plants. Describes current methods for the isolation and identification of xenobiotic conjugates. Provides evidence for and implications of newly discovered novel xenobiotic conjugates and the biological significance and consequences of xenobiotic conjugates.
Sigma-Aldrich offers abstracts and full-text articles by [Katsuhide Igarashi, Satoshi Kitajima, Ken-ichi Aisaki, Kentaro Tanemura, Yuhji Taquahashi, Noriko Moriyama, Eriko Ikeno, Nae Matsuda, Yumiko Saga, Bruce Blumberg, Jun Kanno].
ISSX has an international base of members from more than 45 countries. Members are comprised fairly evenly between academic and industry groups and consist primarily of research scientists and future scientists in toxicology, pharmacology, molecular biology, and other disciplines related to the study of xenobiotics. ...
ISSX has an international base of members from more than 45 countries. Members are comprised fairly evenly between academic and industry groups and consist primarily of research scientists and future scientists in toxicology, pharmacology, molecular biology, and other disciplines related to the study of xenobiotics. ...
Photochemical degradation of hydrophilic xenobiotics in the UV/H2O2-process. Influence of humic matter on the degradation rate of 2-amino-1-naphthalenesulfonate and ...
Spike-in SILAC, in which tissue from a single metabolically labeled mouse can be used as an internal standard in multiple experiments (39), permits large-scale analysis of the proteome without the expensive requirement for maintenance of a labeled mouse colony. Relative quantification of proteins of interest can only be achieved, however, when those proteins are expressed at a detectable level in this animal. We have sought here to create a generic in vivo SILAC material suitable for quantification of as many DME, both basally expressed and requiring induction, as possible. Following simultaneous activation of Pxr, Car, and Ahr, we observed the widespread up-regulation of multiple Cyp, with an increase from 56 unique Cyp-derived peptides in untreated mice to 115 unique peptides following mixture-dosing (Fig. 3A). Crucially, the greatest induction was seen in the "xenobiotic-metabolizing" Cyps of the 1a, 2b, 2c, and 3a subfamilies (Fig. 3A), as opposed to those superfamily members with minor ...
How to Maximize the Use of DMPK and Drug-Drug Interaction Data Available in the Literature and Regulatory Reviews during Clinical Development of New Chemical ...
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Nirmal Bang is of the view that Rashtriya Chemicals has given a break out. The stock has the potential to touch Rs 86 in coming sessions, it says.
Naturally occurring sources refers to psychoactive chemicals or their precursors that already exist in nature. This is in contrast to synthetic psychoactives which are artificially produced or designed in laboratories. These natural chemicals can often be reproduced synthetically as well, though notably they appear in nature or through human cultivation.
During recent years there have been several incidents where symptoms of disease have been linked to consumption of food contaminated by chemical substances (e.g. TCDD). Furthermore, outbreaks of infections in food producing animals have attracted major attention with regards to the safety for consumers (e.g., BSE and influenza in chicken). As shown for several xenobiotics in an increasing number of experimental studies, even low-dose xenobiotic exposure may impair immune function over time, as well as microorganism virulence, resulting in more severe infectious diseases and possibly other diseases as well. Also, during ongoing infection, xenobiotic uptake and distribution is often changed resulting in increased toxic insult to the host. The interactions between infectious agents, nutrients, and xenobiotics have thus become a developing concern and new avenue of research in food toxicology, as well as in food-born diseases. From a health perspective, in the risk assessment of xenobiotics in our ...
Transcriptional regulation of some genes involved in xenobiotic detoxification and apoptosis is performed via the human pregnane X receptor (PXR) which in turn is activated by structurally diverse agonists including steroid hormones. Activation of PX
Nuclear receptor humanized mice models have been developed to predict regulation of drug metabolizing enzyme by xenobiotics. However, limited information is available concerning xenobiotic-induced regulation of drug metabolizing enzymes in multiple nuclear receptor humanized mice. The present study investigated the hepatic regulation of cytochrome P450s (CYPs) and UDP-glucuronosyl-transferases (UGTs) in the pregnane X receptor (PXR) and the constitutive androstane receptor double humanized mice treated with rifampicin (RIF; 10 mg/kg) for 4 days. RIF increased hepatic microsomal protein and total CYP contents, and CYP reductase activity in the humanized mice, but not in normal mice. Moreover, hepatic induction of Cyp2b10, Cyp2c, and Cyp3a11 were observed only in the RIF-treated humanized mice, suggesting that the humanized mice are sensitive to RIF with respect to the regulation of the hepatic CYP system. Hepatic UGT activities using estradiol, serotonin, and mefenamic acid, but not ...
The Journal of Xenobiotics publishes original studies concerning the beneficial (pharmacology) and detrimental effects (toxicology) of xenobiotics in all organisms. A xenobiotic ("stranger to life") is defined as a chemical that is not usually found at significant concentrations or expected to reside for long periods in organisms. In addition to man-made chemicals, natural products could also be of interest if they have potent biological properties, special medicinal properties or that a given organism is at risk of exposure in the environment. Topics dealing with abiotic- and biotic-based transformations in various media (xenobiochemistry) and environmental toxicology are also of interest.. Areas of interests include the identification of key physical and chemical properties of molecules that predict biological effects and persistence in the environment; the molecular mode of action of xenobiotics; biochemical and physiological interactions leading to change in organism health; ...
Püttmann, M., Arand, M., Oesch, F., Mannschreck, Albrecht and Robertson, L. (1990) Chirality and the Induction of Xenobiotic-Metabolizing Enzymes: Effects of the Atropisomers of 2,2;3,4,4;6-Hexachlorobiphenyl. In: Holmstedt, Bo and Frank, H. and Testa, B., (eds.) Chirality and biological activity: proceedings of an international symposium, Tübingen, Federal Republic of Germany, April 5 - 8, 1988. Liss, New York, p. 177. ISBN 0-471-56226-2. Fulltext not available ...
Enzymatic conversion of most xenobiotic compounds is accomplished by hepatocytes in the liver, which are also an important target for the manifestation of the toxic effects of foreign compounds. Most cell lines derived from hepatocytes lack important toxifying or detoxifying enzymes or are defective in signaling pathways which regulate expression and activity of these enzymes. On the other hand, the use of primary human hepatocytes is complicated by scarce availability of cells and high inter-donor variability. Thus, analyses of drug metabolism and hepatotoxicity in vitro are a difficult task. The cell line HC-AFW1 was isolated from a pediatric hepatocellular carcinoma and so far has been used for tumorigenicity and chemotherapy resistance studies. Here, a comprehensive characterization of xenobiotic metabolism in HC-AFW1 cells is presented along with studies on the functionality of the most important transcriptional regulators of drug-metabolizing enzymes. Results from HC-AFW1 cells were ...
Overexpression of BCRP/ABCG2, a xenobiotic efflux transporter, is related to anticancer drug resistance in tumors. Proto-oncogene c-MET induces cancer cell proliferation, motility, and survival, and its aberrant activation was found to be a prognostic factor in advanced ovarian cancers. In this study, we demonstrate the potential cross-resistance of doxorubicin-resistant ovarian cancer cells to the pheophorbide a (Pba)-based photodynamic therapy (PDT) and suggest c-MET and BCRP/ABCG2 overexpression as an underlying molecular mechanism. The doxorubicin resistant A2780 cell line (A2780DR) showed enhanced resistance to PDT cytotoxicity with decreased level of reactive oxygen species generation and Pba accumulation than A2780. In microarray analysis, BCRP/ABCG2 is the sole drug transporter which was upregulated in A2780DR. The incubation with the BCRP/ABCG2 specific inhibitor reversed the both Pba-PDT and doxorubicin resistance in A2780DR. Importantly, we identified that the expression of c-Met, ...
Almost without exception, biological processes such as overt morphological changes, development (both reproductive and growth), toxicological responses and clinical manifestation to disease, have molecular basis. From our perspective (i.e. toxicological perspective), the evidence of receptor-mediated mechanisms of xenobiotic-induced effects is provided if the effect is tissue specific, predictable, if increases in the transactivation of specific genes can be demonstrated, transcriptional responses occur rapidly, compounds bind reversibly to intracellular macromolecules or compounds are stereo-specific. Thus, the primary objective of toxicological in vitro studies on cells and tissues is to characterize cellular and molecular substrates and pathways that contribute to adverse effects in an organism after toxicant exposure. The estrogenic and xenobiotic biotransformation gene expressions are receptor-mediated processes that are ligand structure-dependent interactions with estrogen-receptor (ER) ...
While oxidative stress is a commonly cited toxicological mechanism, conventional methods to study it suffer from a number of shortcomings, including destruction of the sample, introduction of potential artifacts, and a lack of specificity for the reactive species involved. Thus, there is a current need in the field of toxicology for non-destructive, sensitive, and specific methods that can be used to observe and quantify intracellular redox perturbations, more commonly referred to as oxidative stress. Here, we present a method for the use of two genetically-encoded fluorogenic sensors, roGFP2 and HyPer, to be used in live-cell imaging studies to observe xenobiotic-induced oxidative responses ...
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Slide Set: Introduction to Chemical Mixtures. A biologist must be able to work with and understand a variety of mixtures. Dr. David Caprette presents basic concepts and definitions, and the rationale behind descriptions of types of mixtures. Companion slide set for the video, Introduction to Chemical Mixtures.
Urine is also being actively considered as a fertilizer for use in food-crop agriculture in developed countries. Studies into its feasibility and safety usually indicate that it is an acceptable alternative to chemical fertilisers and stabilised sludge. However, the technology to implement its use on a large scale has not been developed, and is considered too expensive. There are also concerns over its safety regarding the potential for transmitting infectious disease and refluxing xenobiotic compounds (associated with toilet-cleaning products and prescribed drugs expelled in urine) in the human food chain. Proponents of adopting urine for this use usually claim the risks to be negligible or acceptable, and point out that sewage causes more environmental problems when it is treated and disposed of compared with when it is used as a resource. Critics generally agree that more research is needed into how the resource is to be collected, processed and handled ...
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Cytochrome P450 3A4 (CYP3A4) plays a central role in xenobiotic metabolism, and is of critical importance to both human health and the pharmaceutical industry. Its ability to interact with multiple molecules of the same ...
The science of toxicology has progressed considerably since Molecular Toxicology was first published in 1997. New advances in biochemical and molecular biological experimental techniques have helped researchers understand the precise effects of toxins and foreign compounds on living things at the molecular, cellular, and organismal levels.
To our knowledge, the current study represents the largest and most comprehensive flow cytometric. Each case was assigned one of the following histological subtypes: ADCA, SCCA, Adeno-squamous,. The largest sample size of centenarians in GWAS studies published. Before the current study, starch, sucrose and xenobiotic metabolism and calcium signaling had not been identified as being.. What Does Threshold Mean In Science Dec 1, 2014. Learners do not just cross a conceptual threshold; they build it as they. chemical and physical behavior" might mean very different things to. "To maintain a high level of much-needed protection, we provided them with a private jet flight," he tweeted. "To support. What does all of this blinking really mean. even. The treatment of bone defects remains one of the largest challenges in musculoskeletal TERM. and in situ differentiation in the absence of any growth factors, small molecular drugs, or genes. This.. 3b). The largest group of transcripts responding after 2 h ...
Xenoestrogens are chemicals that you are exposed to (and are hard to avoid in the modern world) that have an estrogenic effect in your body. Excess exposure to these can cause hormone balance disruptions for both men and women. So if you thought this article was just for the guys, these chemicals can wreak havoc in the body for both guys and gals ...
The Immunotoxicity of Workplace Xenobiotics interagency agreement functions to enhance the immunotoxicological evaluations of humans exposed to quantifiable lev...
The Mammalian Phenotype (MP) Ontology is a community effort to provide standard terms for annotating phenotypic data. You can use this browser to view terms, definitions, and term relationships in a hierarchical display. Links to summary annotated phenotype data at MGI are provided in Term Detail reports.
We used a whole genome approach to identify major functional gene categories (including xenobiotic transporters and metabolizing enzymes) whose expression depends on gestational age. STUDY DESIGN: We compared gene expression profiles of 1st (45-59 days) and 2nd trimester (109-115 days), and C-section term placentae. RESULTS: In 1st trimester placentae, genes related to cell cycle, DNA, aminoacids and carbohydrate metabolism were significantly overrepresented, while genes related to signal transduction were downregulated. In the organism defense category, we identified genes involved in chemical response, metabolism, and transport. Analysis of signal transduction pathways suggested, and subsequently confirmed independently, that the Wnt pathway was regulated by gestational age. CONCLUSIONS: Our study will serve as a reference database to gain insight into the regulation of gene expression in the developing placentae and, thus, allow comparisons with placentae from complicated pregnancies such as those
The aryl hydrocarbon receptor (AhR) is a cytosolic ligand-activated transcription factor that mediates most of the toxic and carcinogenic effects of drugs and environmental toxins collectively known as xenobiotics. Ligand activation of the AhR stimulates the transcription of genes that encode several xenobiotic-metabolizing enzymes. The molecular mechanisms and signaling pathways evoked by the activation of the AhR are becoming increasingly understood and underscore the participation of the AhR in crucial processes, including cellular stress response, proliferation, differentiation, inflammation, and carcinogenesis. Studies now implicate the AhR as an integral part of the multifaceted signal transduction pathway initiated by the exposure of keratinocytes to ultraviolet B radiation (UVB), which is the most ubiquitous hazard to human skin and the principal risk factor for skin cancer. Ligand-dependent activation of the AhR in the cytosol provides a molecular bridge that links cytoplasmic events to ...
The fate of xenobiotics in living organisms is determined by their in vivo absorption, distribution, metabolism and excretion. A convenient and scalable animal model of these biological processes is thus highly beneficial in understanding the effects of xenobiotics. Here we present a silkworm model to investigate the molecular properties-directed absorption, distribution and excretion of fluorescent compounds as model xenobiotics through introducing the compounds into the silkworms diet and monitoring the resulting color and fluorescence in the silkworms body. The efficient uptake of xenobiotics into silk has been further studied through quantitative analysis of the intrinsically colored and highly luminescent silk secreted by silkworm. Our findings provide first-hand insights to better understand the molecular properties that allow specific materials to be incorporated into silk while it is being produced in the silk gland. The use of resulting luminescent silk as scaffold for tissue ...
Manzanares MÁ, de Miguel C, Ruiz de Villa MC et al.. Medical Physiology Unit, Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain.. The Journal of nutritional biochemistry. Feb 2017.. Breast cancer is the most common malignancy among women worldwide. In addition to reproductive factors, environmental factors such as nutrition and xenobiotic exposure have a role in the etiology of this malignancy. A stimulating and a potentially protective effect on experimental breast cancer has been previously described for high corn oil and high extra-virgin olive oil diets, respectively. This work investigates the effect of these lipids on the metabolism of 7,12-dimethylbenz(a)anthracene (DMBA), a polycyclic aromatic hydrocarbon that can initiate carcinogenesis and its consequences in an experimental rat breast cancer model. The PUFA n-6-enriched diet increased expression of Phase I enzymes prior to DMBA ...
Manzanares MÁ, de Miguel C, Ruiz de Villa MC et al.. Medical Physiology Unit, Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain.. The Journal of nutritional biochemistry. Feb 2017.. Breast cancer is the most common malignancy among women worldwide. In addition to reproductive factors, environmental factors such as nutrition and xenobiotic exposure have a role in the etiology of this malignancy. A stimulating and a potentially protective effect on experimental breast cancer has been previously described for high corn oil and high extra-virgin olive oil diets, respectively. This work investigates the effect of these lipids on the metabolism of 7,12-dimethylbenz(a)anthracene (DMBA), a polycyclic aromatic hydrocarbon that can initiate carcinogenesis and its consequences in an experimental rat breast cancer model. The PUFA n-6-enriched diet increased expression of Phase I enzymes prior to DMBA ...
Abstract. Liver is considered as the first target for the toxic effects of toxins and other xenobiotics, and this can be attributed to its role as a site which receive all absorbed xenobiotics from the gastrointestinal tract and its role as a major site for biotransformation of xenobiotics. The present study was designed to evaluate the possible hepatoprotective effect of benfotiamine against CCl4-induced hepatotoxicity in rats. The study was conducted on 48 male albino rats; the animals were allocated into 8 groups (6 rats in each group) and treated as follow: 4 groups treated with oral doses of either normal saline, benfotiamine (100 mg/kg), thiamine (100 mg/kg), N-acetylcystein (400 mg/kg) only without induction of hepatic damage. The other 4 groups were treated as indicated previously with induction of hepatic damage with CCl4; at the end of treatment period, rats were scarified, blood samples obtained and livers excised for the assessment of the oxidative stress parameters (MDA and GSH), ...
Cisplatin is reported to increase intracellular ROS and 8-oxodG levels (27). As Fpg and α-OGG1 overexpression has been shown to lower 8-oxodG and oxypurine-clustered DNA damage levels, and OGG1-deficient mice exhibit tissue-specific increases in 8-oxodG accumulation following ROS-inducing xenobiotic exposure (12-16, 55), we measured nuclear 8-oxodG/dG ratios in untreated and drug-treated cell clones (Fig. 5E and F). Ectopic expression of Fpg (clone fpg 6a) or α-OGG1 (clone OGG1 1d) significantly lowered endogenous nuclear 8-oxodG levels compared with the pC 1c clone control. In addition, stable transgene expression markedly inhibited an immediate increase in 8-oxodG generation following cisplatin treatment (30 μmol/L; Fig. 5E). A maximal 1.5-fold increase in 8-oxodG/dG occurred 30 minutes after treatment compared with untreated sample and was diminished by 2 hours after treatment. Oxaliplatin exposure produced a slightly lower increase in 8-oxodG/dG that also was inhibited in fpg and α-OGG1 ...
The body removes xenobiotics by xenobiotic metabolism. Hepatic CYP2B6 enzymes are responsible for the metabolism of Xenobiotics by first activating them. An example of a enzyme involved in xenobiotic metabolism is hepatic microsomal cytochrome P450 Myristicin from parsley leaf oil [5-allyl-1-methoxy-2,3-(methylenedioxy) benzene, known to produce significant psychopharmacological responses as well as insecticidal activity.] a chemopreventive agent detoxified by the mu class GST might occur through an Ah [the Hepa-1 cytosolic aryl hydrocarbon (Ah)] receptor-independent pathway. Indicated that the saturation of the isolated double bond a mechanism for its inhibition of B[a]P [benzo[a]pyrene] or other carcinogens that may be detoxified in the same manner. Involves increases in mRNA levels except in the case of P4502E1. These metabolites were excreted [confirmed in urine] as conjugated forms as well, clones are sequence-verified shRNA lentiviral plasmids particles at 106 TU/ml the parental vector ...
When examining molecular actions of xenobiotics on neurotransmitter systems, it quickly becomes apparent that substances rarely possess single pharmacologic actions. As examples, doxepin, in part, antagonizes voltage-gated sodium channels, histaminic H1 and H2 receptors, α-adrenergic receptors, muscarinic acetylcholine receptors, dopamine D2 receptors, and GABAA receptors; prevents potassium efflux; and inhibits norepinephrine, serotonin, and adenosine uptake. Similarly, carbamazepine blocks voltage-gated sodium channels; inhibits uptake of norepinephrine, adenosine, and serotonin; antagonizes adenosine and muscarinic receptors; activates GABAB receptors; and binds to benzodiazepine-binding sites on mitochondria. For obvious reasons, then, this chapter cannot include every action of every xenobiotic on the nervous system. Nor is it meant to be a complete discussion of toxic syndromes produced by various xenobiotics, as these are discussed in specific chapters. Rather, this chapter provides a ...
The American College of Toxicology (ACT) is offering an advanced course, "Advanced Comprehensive Toxicology," to complement "Toxicology for Pharmaceutical and Regulatory Scientists." In this five-day intensive course, attendees will be provided detailed descriptions of the principles of toxicology, effects of xenobiotics on organ systems, discussions of specific classes of toxicants, mechanisms of toxicity, risk assessment, and other contemporary toxicological concepts. The content of this course will provide information that could be helpful to those seeking certification in toxicology or to those seeking more advanced training in toxicology. The faculty consists of well-recognized experts in their field of study and most are Board Certified by the American Board of Toxicology.. This week-long course will begin on Sunday evening with an orientation and reception and will end on Friday with a practice exam, comprised of questions with the type and rigor found on the American Board of Toxicology ...
Abstract Background There are no known causes for progressive supranuclear palsy (PSP). The microtubule associated protein tau (MAPT) H1 haplotype is the major genetic factor associated with risk of PSP, with both oxidative stress and mitochondrial dysfunction also implicated. We investigated whether specific single nucleotide polymorphisms (SNPs) in genes encoding enzymes of xenobiotic detoxification, mitochondrial functioning, or oxidative stress response, including debrisoquine 4-hydroxylase, paraoxonase 1 and 2, N-acetyltransferase 1 and 2 (NAT2), superoxide dismutase 1 and 2, and PTEN-induced putative kinase are associated with PSP. Methods DNA from 553 autopsy-confirmed Caucasian PSP cases (266 females, 279 males; age at onset 68 ± 8 years; age at death 75 ± 8) from the Society for PSP Brain Bank and 425 clinical control samples (197 females, 226 males; age at draw 72 ± 11 years) from healthy volunteers were genotyped using Taqman PCR and the SequenomiPLEX Gold assay. Results The ...
The mechanisms involved in the recognition of microbial pathogens and activation of the immune system have been extensively studied. However, the mechanisms involved in the recovery phase of an infection are incompletely characterized at both the cellular and physiological levels. Here, we establish a Caenorhabditis elegans-Salmonella enterica model of acute infection and antibiotic treatment for studying biological changes during the resolution phase of an infection. Using whole genome expression profiles of acutely infected animals, we found that genes that are markers of innate immunity are down-regulated upon recovery, while genes involved in xenobiotic detoxification, redox regulation, and cellular homeostasis are up-regulated. In silico analyses demonstrated that genes altered during recovery from infection were transcriptionally regulated by conserved transcription factors, including GATA/ELT-2, FOXO/DAF-16, and Nrf/SKN-1. Finally, we found that recovery from an acute bacterial infection ...
Duque, E., Molina-Henares, A.J., De La Torre, J., Molina-Henares, M.A., Del Castillo, T., Lam, J., and Ramos, J.L. (2007a) Towards a genome-wide mutant library of Pseudomonas strain KT2440. In Pseudomonas: A Model System in Biology. Vol. V. Ramos, J.L., and Filloux, A. (eds). Dorchester, the Netherlands: Springer, pp: 227-251 ...
... - Adrenochrome Monosemicarbazone is a haemostatic with a rapid onset of action . It contains a water soluble form of adrenochrome monosemicarbazone.
Founded in 1983, the Gentest brand initially focused on the use of cultured human cells in GLP genotoxicity assays. In 1985, the company expanded research activities into the area of xenobiotic metabolism by developing cytochrome P450 cDNA-expression approaches. This led to the first commercial offering of cDNA-expressed human cytochrome P450 enzymes in 1990. Since that time, the range of Gentest offerings has increased dramatically, from recombinant systems to in vivo-like systems like primary hepatocytes. Now, as part of Corning Life Sciences, the Gentest offerings continue to grow, helping you stay on the leading edge of drug discovery and development.. Our scientists are internationally recognized as leaders and innovators in cytochrome P450 cDNA-expression, in vitro xenobiotic metabolism, and drug transporter techniques. Our demonstrated commitment to research has been rewarded by the receipt of several competitive NIH grants. The results and applications of our research are reported in ...
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This chapter discusses the aspects of bioremediation that are related to metabolism of recalcitrant chemicals by bacteria, leaving out also detoxification and immobilization of metal ions and metalloids. The most frequent types of sites amenable to bioremediation include soil, freshwater, seawater, and sediments. The chapter talks about the instances where recalcitrant and/or xenobiotic compounds are endowed with chemical properties that cause a deleterious effect on the catalytic microorganisms present in the site-regardless of whether they can be ultimately metabolized. The chemicals at stake include metals, chaotropic agents, aromatics, and hydrophobic compounds. These stressors can be grouped based on their effect on bacterial metabolism. Heat shock-like stress and oxidative damage are certainly the two more prevalent conditions endured by environmental bacteria during in situ biodegradation of chemical waste. This is true for singular stressors as well as for mixtures of them, the most frequent
There are only a few testing strategies directed specifically at female reproductive toxicity. (Generoso et al, 1971; Generoso and Cosgove, 1973; Bishop et al., 1997). There are some elegant...
The influence of resident gut microbes on xenobiotic metabolism has been investigated at different levels throughout the past five decades. However, with the advance in sequencing and pyrotagging technologies, addressing the influence of microbes on
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Every time your dogs (and other pets!) put something in their mouths they are being exposed to chemicals, many of which may be toxic and cause cancer. It might be time to take a second look at your household products.
Testing of your own hormones usually does not help clinically because many of the cosmetics and toiletries contain various chemicals and herbs that are estrogenic (xenoestrogens). These xenoestrogens do NOT show up on the hormone test.
The aim of this volume is to present data from a systemic analysis of the dynamics state of glutathione, because it is believed that this analysis is critical and essential for a better understanding of pharmacotoxicological (defense against xenobiotics…
This project investigates metabolic events associated with food, nutrients, and xenobiotics using a high-resolution mass spectrometer. MSI is providing storage for this data as well as resources for data processing and analysis.. ...
Cell to cell via gap junctions. Chemical messengers in ECF: neural (neurotransmitters at synapses), endocrine (hormones and growth factors), paracrine (products of cells diffuse to neighbours), Autocrine = cell secretes messenger that acts on itself. Same chemical can function in several ways. Juxtacrine = molecules attached to membrane that attaches to another cell.. ...
Background: The exposome represents the accumulation of all environmental exposures across a lifetime. Top-down strategies are required to assess something this comprehensive, and could transform our understanding of how environmental factors affect human health. Metabolic profiling (metabonomics/metabolomics) defines an individuals metabolic phenotype, which is influenced by genotype, diet, lifestyle, health and xenobiotic exposure, and could also reveal intermediate biomarkers for disease risk that reflect adaptive response to exposure. We investigated changes in metabolism in volunteers living near a point source of environmental pollution: a closed zinc smelter with associated elevated levels of environmental cadmium. Methods: High-resolution [superscript 1]H NMR spectroscopy (metabonomics) was used to acquire urinary metabolic profiles from 178 human volunteers. The spectral data were subjected to multivariate and univariate analysis to identify metabolites that were correlated with ...
The constitutive androstane receptor (CAR, NR1I3) is a central regulator of xenobiotic metabolism. CAR activation induces hepatic expression of detoxification enzymes and transporters and increases liver size. Here we show that CAR-mediated hepatomegaly is a transient, adaptive response to acute xen …
GST Pi is a member of the glutathione-S-transferase superfamily of phase II xenobiotic-metabolizing enzymes that catalyse the conjugation of endogenous and exogenous electrophiles, including reactive oxygen species, toxins, carcinogens and anti-cancer agents, to the nucleophilic thiol group of reduced glutathione (GSH) [12]. A number of studies have concentrated on the connection between aberrant expression of GST isozymes, including GST Pi isozymes, with the development and expression of resistance to chemotherapy drugs as reviewed by McIlwain et al.[13]. From this perspective an expected result should have been a poor response to chemotherapy in patients with high expression of GST Pi. However our study has shown that, for stage C colon cancer patients, overall survival was significantly and markedly poorer in patients with high GST Pi who did not receive chemotherapy than in those with high GST Pi who did. Furthermore, survival in the latter group was no different from that in patients with ...
2.A.60 The Organo Anion Transporter (OAT) Family. Proteins of the OAT family (solute carrier family 21 (previously called SLC21A; more recently designated SLCO by the HUGO Gene Nomenclature Committee (B. Hagenbuch, personal communication))) catalyze the Na+-independent facilitated transport of fairly large amphipathic organic anions (and less frequently neutral or cationic drugs) such as bromosulfobromophthalein, prostaglandins, conjugated and unconjugated bile acids (taurocholate and cholate, respectively), steroid conjugates such as estrone-sulfate and dehydroepiandrosterone-sulfate (Rižner et al. 2017), thyroid hormones, anionic oligopeptides, drugs, toxins and other xenobiotics (Hong 2013). Among the well characterized substrates are numerous drugs including statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, antibiotics, antihistaminics, antihypertensives and anticancer drugs (Hagenbuch and Stieger 2013). There are six mammalian OAT families (Hagenbuch and ...
Intestinal biotransformation of drugs and dietary xenobiotics may be modified during maturation and aging. The main purpose of this study was to estimate the level of expression and inducibility of selected intestinal CYP450 mRNAs in various phases of rat life. Biochemical analysis of the cytochrome P450 and cytochrome b5 reductases activity in function with age was the second but also important aim of the presented work. However, it should be explicitly stressed that the results of this experiment do not concern the age-related drug metabolism and disposition in humans. Under conditions of our experiment, constitutive CYP1A1 mRNA expression was lowest in the small intestine of 2-week-old rats and was increased in sexually mature 2-month-old animals. Since the attainment of maturity, the animals showed relatively constant levels of constitutive CYP1A1 mRNA. Such a stable expression persisted till the advanced animal age, when its significant augmentation was observed. These data may indicate ...
Kono. 2002. A genetic analysis of lupus. Allergy 57 Suppl 72:67-74. Croker, B. , G. Gilkeson, and L. Morel. 2003. Genetic interactions between susceptibility loci reveal epistatic pathogenic networks in murine lupus. Genes Immun 4:575-585. , X. H. Tian, B. P. Croker, and E. K. Wakeland. 1999. Epistatic modifiers of autoimmunity in a murine model of lupus nephritis. Immunity 11:131-139. , J. Kappler, and B. L. Kotzin. 2001. Autoimmune disease: why and where it occurs. Nat Med 7:899-905. Rubin, R. 2002. Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation. J Clin Invest 109:41-50. , B. Krammer, and G. Schwamberger. 1999. Cutting edge: differential effect of apoptotic versus necrotic tumor cells on macrophage antitumor activities. J Immunol 163:1730-1732. Pollard, K. , D. L. Pearson, M. Bluthner, and E. M. Tan. 2000. Proteolytic cleavage of a self-antigen following xenobiotic-induced cell death produces a fragment with novel ...
Superfund site xenobiotics and other environmental toxicants are human health hazards whose toxicity is, in part, associated with altered patterns of gene expression. The goal of this project is to provide molecular mechanisms and models for exposure, focusing on the
Avilova O. Microscopic features of the spleen under the impact of xenobiotics / O. Avilova, C. Mathew John // ISIC-2018 : [International Scientific Interdisciplinary Conference for medical students and young scientists, Kharkiv, 23-25 May, 2018] : abstract book / KNMU. - Kharkiv, 2018. - P. 13-14 ...
Xenobiotics, such as amiloride, MPP+, and quinine, that are transported at low rates by the mammalian luminal OC exchanger and compete for the OC binding site on the carrier, are known to trans-inhibit OC transport (Lazaruk and Wright, 1990;Rafizadeh et al., 1986; Sokol et al., 1987;Wright and Wunz, 1987). Likewise, several xenobioticstrans-inhibited TEA efflux from avian renal BBMV (fig. 3). The relatively low transport capacity for these and other xenobiotic substrates may be a direct, but adverse consequence of the high-affinity binding of the substrate to the exchanger. Kinetic analyses conducted on rabbit renal BBMV determined that amiloride and quinidine were competitive inhibitors of OC/H+exchange (Wright and Wunz, 1987; Ott et al., 1991). Preliminary kinetic analysis suggested that the inhibitory potency and low transport efficacy of amiloride, procainamide and quinidine may possibly involve allosteric interactions; however, based on these preliminary data, it cannot be said whether ...
Biologist Philip A. Rea has been named a Fellow of the American Association for the Advancement of Science (AAAS) for his fundamental discoveries on the membrane transport and detoxification of xenobiotics and his distinguished accomplishments and creativity in science education.. Xenobiotics are chemical compounds, such as drugs or carcinogens, that are foreign to a living organism. Rea, a professor of biology and the Belldegrun Distinguished Director of the Vagelos Program in Life Sciences and Management, focuses his research on molecular biology and cellular biochemistry with special emphasis on membrane transport proteins and the enzymatic machinery responsible for the detoxification of xenobiotics, especially heavy metals. Along with better understanding transport and related phenomena, Reas research may eventually contribute to ways to eliminate toxins from living organisms or the environment.. Rea is the author of a variety of publications, and has received teaching awards including the ...
Cytochrome p450s comprise a superfamily of heme-thiolate proteins named for the spectral absorbance peak of their carbon-monoxide-bound species at 450 nm. Having been found in every class of organism, including Archaea, the p450 superfamily is believed to have originated from an ancestral gene that existed over 3 billion years ago. Repeated gene duplications have subsequently given rise to one of the largest of multigene families. These enzymes are notable both for the diversity of reactions that they catalyze and the range of chemically dissimilar substrates upon which they act. Cytochrome p450s support the oxidative, peroxidative and reductive metabolism of such endogenous and xenobiotic substrates as environmental pollutants, agrochemicals, plant allelochemicals, steroids, prostaglandins and fatty acids.
Its a new year and I thought I would bring out the molecule I had intended to write about in November, I thought I would focus on another topic that links to the theme of malaria (at the UTC) , but which is of wider importance in understanding the way animals, in particular, deal with chemical challenges. The cytochrome P450 family of proteins (often abbreviated to CYPs; an example is shown on the LHS), is an important target for insecticides (take a look at the links at Nicole Joussens web site in Germany) in dealing with the spread of malaria via mosquitoes, but it is also an important class of enzymes in the process of drug validation (I like the way Emily Scott has organised her research into CYPs and drug discovery here [and then follow her research links]). The first thing to say is that it isnt a single enzyme. The CYPs are a group of enzymes which facilitate the "metabolism" of foreign compounds (xenobiotics). From an evolutionary perspective, they provide a selective advantage in ...
Cytochromes P450 (P450) are a ubiquitous class of monooxygenases located in the endoplasmic reticulum of mammalian cells. These enzymes catalyse the Phase I oxidative metabolism of a wide range of structurally diverse chemicals resulting in increased hydrophilicity and excretion. Certain chemicals are, however, metabolically activated by cytochrome P450, leading to the formation of cytotoxic and/or carcinogenic metabolites. This has been exploited in the design of many prodrugs, including anti-tumour agents, which are inactive as administered but become active in vivo following metabolism by one or more of the P450 isozymes. The regulation of P450 gene expression has been well documented in experimental animals, but at present there is very little information available about the regulation of human P450 genes, particularly in extra-hepatic tissues. Regulation of P450 expression by a range of xenobiotics, known to have profound effects on the expression of rodent P450 genes, has been studied in a ...
Author: Jake Paul Fratkin. Title: How Environmental Toxins Can Make You Sick. Summary: Environmental toxins have created burdens on the human body that put demands beyond our evolutionary development.
Discussion about Adrenochrome. The most disgusting, secret, elite LSD/Crack-like high in blood drinking that explains almost everything. [Page 6] at the GodlikeProductions Conspiracy Forum. Our topics include Conspiracy Theory, Secret Societies, UFOs and more!
BIO TRANSFORMATION The human body is constantly in the presence of potentially harmful substances. Luckily it has the capacity to detoxify foreign compounds through various physical methods, one of them being the liver. The liver plays a central role in metabolic detoxification, but its effectiveness depends largely on the hosts physical functioning and biochemical status. Biotransformation is the process of chemical alteration of a substance within the body by the action of enzymes. Bio transformation is a key defense…. Read More. ...
Biomed Pap Med Fac Univ Palacky lomouc Czech Repub Jun; 154(2): P. Jancova, P. Anzenbacher, E. Anzenbacherova 103 PASE II DRUG METABLIZIG EZYMES Petra Jancova a *, Pavel Anzenbacher b, Eva
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Validation of Test Methods for Assessing Neurodevelopment in Children, University of Rochester School of Medicine and Dentistry and Rutgers University
What is Detoxification? Detoxification is the process of removing substances considered toxic or poisonous to the human body. Detoxification aims at the mobilization and excretion of the toxic properties of the substance by inducing chemical changes in the body. The primary organs of detoxification are the liver, skin, bowels, and lungs. Why is detoxification so…
rat Cyp4a14 protein: cytochrome P-450 enzyme that oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics, RefSeq NM_175760
Citation: Bishop, JB, Morris, RW, Seely, JC, Hughes, LA, Cain, KT, Generoso, WM. Alterations in the Reproductive Patterns of Female Mice Exposed to Xenobiotics. Fund. and Appl. Tox. 40: 191-204 (1997 ...
There is little information available to scientists about which compounds are used during hydraulic fracturing. What they do know is that at least eight commonly used fracking chemicals are toxic to mammals.
We offer clinical cancer updates, treatment guidance, and research news to the oncology nursing community. Visit us often for drug therapy testing results, patient care information and more. Download our FREE app today.
From past 5 years we have been supporting all Domestic markets for Impurities & API in USA, Impurities & API in Canada and Impurities & API European countries. Rxn Chemicals can support for all Impurities which are acceptable to all regulatory agencies in the world, US-FDA, MHRA, MCC, WHO, Brazil, Japan. ...
Detoxification is the process of reducing or eliminating the toxins that are present in your body. In many illnesses this is a vital pathway to health. At
Transmembrane P-glycoproteins (P-gps) are responsible for multidrug resistance (MDR) phenotypes in tumor cell lines. P-glycoproteins function as energy dependent efflux flippases that prevent the cellular accumulation of a wide variety of compounds. We characterized P-gp expression in populations of several fish species exposed in their natural habitat to environmental contaminants which may be P-gp substrates/inducers. We evaluated whether P-gp activity may be implicated in this multixenobiotic resistant phenotype. In winter flounder (Pleuronectes americanus) with contaminant-associated liver tumors, P-gp was highly expressed in bile canaliculi of non-tumorous liver surrounding cholangiocellular carcinoma, but was not detected within tumors. Cellular stress caused by impaired bile elimination may be responsible for elevated P-gp. Killifish (Fundulus heteroclitus) from a contaminated field sites had higher intestinal P-gp and lower hepatic P-gp than control killifish. In contaminated fish, ...
The constitutive androstane receptor (CAR) also known as nuclear receptor subfamily 1, group I, member 3 is a protein that in humans is encoded by the NR1I3 gene. CAR is a member of the nuclear receptor superfamily and along with pregnane X receptor (PXR) functions as a sensor of endobiotic and xenobiotic substances. In response, expression of proteins responsible for the metabolism and excretion of these substances is upregulated. Hence, CAR and PXR play a major role in the detoxification of foreign substances such as drugs. Androstenol and several isomers of androstanol, androstanes, are endogenous antagonists of the CAR, and despite acting as antagonists, were the basis for the naming of this receptor. More recently, dehydroepiandrosterone (DHEA), also an androstane, has been found to be an endogenous agonist of the CAR. CAR is a member of the nuclear receptor superfamily, and is a key regulator of xenobiotic and endobiotic metabolism. Unlike most nuclear receptors, this transcriptional ...
Kirtan Kaur, M.S., M.Phil., is a graduate student at New York University Langone Health Center, working towards a Ph.D. in environmental/public health and toxicology. Her research interest and focus reside in the area of developmental toxicology; assessing how xenobiotic exposures during pregnancy can impact fetal development, increasing susceptibility to adverse health outcomes in later life. She is conducting her dissertation research on human placental samples collected from a birth cohort study to discern the effects of gestational air pollution exposure on placental gene expression and how that impacts fetal growth. She graduated from MMC in 2012 with a B.S. in Biology and a minor in Environmental Studies . ...