Drug metabolism in cell toxicity potential idiosyncratic toxicities. Medical search. Frequent questions

Phenytoin-initiated micronucleus formation was increased about 4-fold in both +/ j (P = .006) and j/j (P = .009) UGT-deficient cells vs. +/+ UGT-normal cells, providing the first evidence that the bioactivation and oxidative toxicity of phenytoin itself may be avoided by direct N -glucuronidation, which was confirmed by tandem mass spectrometry. (aspetjournals.org)
Amiodarone shows typical toxicity associated with redox cycling agents: inhibition of electron transport in oxidative phosphorylation plus inhibition of fatty acid β-oxidation, which causes steatosis. (toxbank.net)
Kroll A(1), Pillukat MH, Hahn D, Schnekenburger J. The in vitro assays covered baseline toxicity in bacteria, oxidative stress, cytotoxicity in mammalian cells and yeast, estrogenicity, and anti-androgenicity. (holocausto.online)
H … In vitro assays covered baseline toxicity, oxidative stress responses, and estrogenic and antiandrogenic activity. (holocausto.online)

Fluoroquinolone therapy and idiosyncratic acute liver injury: a population-based study. (greenmedinfo.com)
Traditionally, the in vitro toxicity assays that have been used to identify molecules that carry drug-related DILI risk factors include two-dimensional (2D) cell systems and other standard preclinical model… The principal application of this assay is to rapidly screen test compounds to identify those that induce acute liver cell toxicity. (holocausto.online)

Statin drugs increase the risk of diabetes and cause abnormal liver enzyme elevations. (greenmedinfo.com)

Additionally, NCTR scientists have developed MitoChips for human and non-human primates for better prediction of toxicity, in addition to our findings in rodents. (fda.gov)
Prediction of Chemical Carcinogenicity in Rodents from in Vitro Genetic Toxicity Assays R AYMOND W. TENNANT, BARRY H. MARGOLIN, MICHAEL D. SHELBY, E RROL Z … As an in vivo toxicity endpoint, the acute lung inflammogenicity in a rat instillation model was compared with the in vitro toxicity endpoints comprising cytotoxicity, pro-inflammatory cytokine expression, or haemolytic potential. (holocausto.online)

or exemplifies an in vitro mechanism underlying one of these toxicities. (toxbank.net)
Additional references under Biochemical mechanism of toxicity. (toxbank.net)
On this page you will find links to comprehensive gene information for five species and a listing of NCTR publications on understanding the mechanism of mitochondrial toxicity and development of biomarkers to predict toxicity. (fda.gov)
Because there are FDA-regulated drugs (e.g., anti-HIV drugs, anti-cancer drugs) that cause mitochondrial injury, it is important to understand the mechanism of mitochondrial injury and to develop measures for prevention of mitochondrial damage. (fda.gov)
NCTR has published several papers illustrating the mechanism of mitochondrial toxicity in response to different drugs in the mouse and rat. (fda.gov)
While mitochondrial energy is vital for the survival of cells, these organelles also play an important role in the execution of apoptosis (programmed cell death), a process that serves as a major defense mechanism to remove unwanted and potentially dangerous cells. (fda.gov)

Rarely, bicalutamide has been associated with serious liver toxicity and lung disease, as well as sensitivity to light. (wikipedia.org)
Rarely, an acute idiosyncratic hepatocellular injury resembling viral hepatitis or cholestatic hepatitis occurs. (toxbank.net)

UDP-Glucuronosyltransferases (UGTs) are important in the elimination of most xenobiotics, including 5-( p -hydroxyphenyl)-5-phenylhydantoin (HPPH), the major, reputedly nontoxic, metabolite of the anticonvulsant drug phenytoin. (aspetjournals.org)
The glucuronidation and elimination of endogenous compounds ( e.g. , bilirubin) and xenobiotics, including HPPH, the major, para -hydroxylated metabolite of the anticonvulsant drug phenytoin (diphenylhydantoin) ( Butler, 1957 ), are catalyzed by a superfamily of membrane-bound isozymes known collectively as UGTs ( Dutton, 1980 ). (aspetjournals.org)
Xenobiotics include drugs, industrial chemicals, naturally occurring poisons and environmental pollutants. (iloencyclopaedia.org)
Human lungs are susceptible to the toxicity induced by soluble xenobiotics. (holocausto.online)

In vitro toxicity assays are used to determine the potential of a new pharmaceutical, agrochemical, food additive, or other chemical product to be hazardous to humans.In vitro studies, which are performed on cultured bacterial or mammalian cells, can be used as an initial screen to avoid the unnecessary use of animals in determining which candidates should move forward for further safety testing. (holocausto.online)
The application of High Content Screening for in vitro toxicity testing is a relatively new approach in the preclinical research phase of drug development. (holocausto.online)
In regulatory testing situation these in vitro toxicity assays must be reliable, because from these tests it is only possible to generalize the data to … First Published 1995. (holocausto.online)
While toxicity test has been traditionally completed in the preclinical phase, in vitro toxicity studies in the early drug discovery stages could significantly reduce failures at a later stage and prevent economic loss. (holocausto.online)
Considering the ethical issues and the cost of in-vivo animal tests, the pharmaceutical industry now relies more on in-vitro methods for toxicity testing in the drug development phase. (holocausto.online)
In vitro, chemicals such as drugs and pesticides have different cytotoxicity mechanisms such as destruction of cell membranes, prevention of protein synthesis, irreversible binding to receptors etc. (holocausto.online)
The positive control induced a high degree of toxicity in all in vitro tests performed, indicating that the toxicity observed in the direct contact assay was due to in situ extraction of toxic components. (holocausto.online)

The anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) have been administered to patients with ALK-positive non-small cell lung cancer for a long period of time and show a promising response. (biomedcentral.com)
With the discovery of anaplastic lymphoma kinase (ALK) rearrangements, small-molecule ALK tyrosine kinase inhibitors (TKIs) become the most active therapeutic areas of study in ALK-positive non-small-cell lung cancer (NSCLC) patients. (biomedcentral.com)

Biochemical mechanisms in drug-induced liver injury: Certainties and doubts World J Gastroenterol. (toxbank.net)

Clearance is effected primarily by metabolism in the liver, but metabolism occurs in other tissues as well. (nih.gov)

The effect on mitochondrial membrane potential is biphasic, with increased potential at low dose and decreased potential at high dose, implying multiple points of interaction. (toxbank.net)
This NCTR MitoChip webpage is created to provide comprehensive knowledge and resources on mitochondrial function, mitochondrial injury, and mitchondrial toxicity, while also reporting progress on NCTR's contributions to mitochondrial research. (fda.gov)
MitoChip is a tool to evaluate the change in mitochondrial gene expression in response to various agents including drugs. (fda.gov)
Mitochondrial dysfunction has been implicated in the toxicities of certain diseases and many drugs. (fda.gov)

Therefore, we performed a pooled analysis of the occurrence of severe (grade ≥ 3) toxicity according to the ALK-TKI type based on data extracted from clinical trials of ALK-positive NSCLC patients. (biomedcentral.com)
Liver failure and damage are rare but severe unintended consequences of statin drug use. (greenmedinfo.com)
Hepatotoxicity (toxic effects on the liver) and cardiotoxicity (toxic effects on the heart) are the most severe problems encountered in drug development and the major reason for drug withdrawals. (holocausto.online)

The notion that testing chemicals on animals could be predictive of human responses and therefore should be legally mandated dates back to the 1930s, when the sulfa drugs were being introduced for infections. (biomedcentral.com)
Toxicity classification concerns the grouping of chemicals into general categories according to their most important toxic effect. (iloencyclopaedia.org)

We performed a comprehensive search of the MEDLINE, EMBASE, WEB OF SCIENCE and COCHRANE databases from the drugs' inception to May 2016 to identify clinical trials. (biomedcentral.com)
In clinical, toxicity profiles are usually as deciding factors for clinicians when selecting an effective regimen for ALK-positive NSCLC. (biomedcentral.com)
Features that represent a direct effect of the drug on the liver and that are common to the majority of long-term recipients are ultrastructural phospholipidosis, unaccompanied by clinical liver disease. (toxbank.net)
Therefore, toxicity testing is strictly controlled and has to be performed in animals and in GLP (Good Laboratory Practice) conditions to select a safe starting dose for the clinical trial in humans. (holocausto.online)

Toxicity rating and toxicity classification can be used for regulatory purposes. (iloencyclopaedia.org)

Asymptomatic "foamy cell" phospholipidosis is common, but acute and chronic life-threatening epithelial cell apoptosis with fibrosis and inflammatory responses are observed with significant frequency. (toxbank.net)
Extraction and direct contact assays were performed using human epidermal keratinocytes and mouse fibroblasts and mouse epithelial cells. (holocausto.online)

A dose-effect curve may be obtained at the level of the whole organism, the cell or the target molecule. (iloencyclopaedia.org)

In this review, we will explain the current state and future perspective of computational toxicology related to drug safety assessment from the viewpoint of ontology thinking. (go.jp)
We conduct cytotoxicity estimation using a panel of cell proliferation and viability tests, which can be sorted into four types by different endpoints: Functional assays: assessment of ATP, ADP, ATP/ADP ratios. (holocausto.online)

These reactive intermediates and reactive oxygen species can irreversibly damage DNA, proteins and lipids via covalent binding and oxidation, potentially initiating teratogenesis and other toxicities. (aspetjournals.org)

Additionally, the best treatment response with the lowest possible toxicity should be obtained in selecting patients with consideration for their complications and treatment regimen. (biomedcentral.com)
This minimal evidence may represent an atypical pharmacogenomic response but suggests the need for further investigation, including potential benefit of nutrient supplementation. (interactionsguide.com)
We further analyze the predictive value of animal models when used as test subjects for human response to drugs and disease. (biomedcentral.com)

and the limiting toxicity in humans is normally pulmonary, with adverse events observed in 5% of patients. (toxbank.net)
Chemotherapeutic agents interact with vitamin A in various ways, from adjunctive vitamin A for nutritive support and amelioration of adverse drug effects to cotherapy using retinoids as chemotherapeutic agents. (interactionsguide.com)
Concurrent supplementation with multivitamin providing modest levels of A, D, E, and K with folate, carotenoids, and mixed tocopherols can counter potential adverse effects with little risk and minimal expense. (interactionsguide.com)

The cationic amphiphilic drug and its major metabolite desethylamiodarone accumulate in hepatocyte lysosomes and mitochondria and in bile duct epithelium. (toxbank.net)

At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed. (nih.gov)

Concomitant use may enhance drug efficacy by mobilizing hepatic stores and elevating plasma concentrations, particularly in very-low-birth-weight (VLBW) neonates with bronchopulmonary dysplasia. (interactionsguide.com)

Furthermore, in the "Go" or "No-Go" decision of drug development, supportive utilization of a scientifically interpretable computational toxicology system is required for human safety evaluation. (go.jp)
We conclude that the requirements for animal testing found in the Nuremberg Code were based on scientifically outdated principles, compromised by people with a vested interest in animal experimentation, serve no useful function, increase the cost of drug development, and prevent otherwise safe and efficacious drugs and therapies from being implemented. (biomedcentral.com)

For example, nickel nanoparticles (NiNPs) are used in electric capacitors, and their consumption is increasing, but there have been few reports of their toxicity and environmental effects. (go.jp)
Toxicity rating is an arbitrary grading of doses or exposure levels causing toxic effects. (iloencyclopaedia.org)

Sulfa drugs were some of the first drugs that were shown to be effective against certain bacterial infections, but they were difficult to dissolve in solution. (biomedcentral.com)

Mitomycin is contraindicated in patients who have demonstrated a hypersensitive or idiosyncratic reaction to it in the past. (nih.gov)

The human body is made up of trillions of cells (basic unit of life). (fda.gov)

Retinoid use requires close monitoring by experienced clinicians collaborating on integrative strategy, particularly given significant risk of toxicity. (interactionsguide.com)

Next generation ALK TKIs (ceritinib and alectinib) came into our sight and approved by the United States (US) Food and Drug Administration (FDA) for treated patients with crizotinib-intolerant, crizotinib-progressive or crizotinib-resistant ALK-positive NSCLC ( http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208434s000lbl.pdf , www.accessdata.fda.gov/drugsatfda_docs/label/2014/205755lbl.pdf34s000lbl.pdf ). (biomedcentral.com)

Hazard is the potential for the toxicity to be realized in a specific setting or situation. (iloencyclopaedia.org)

The most common ratings concern acute toxicity. (iloencyclopaedia.org)

The antiarrhythmic effect of Amiodarone is due to at least two major properties: a prolongation of the myocardial cell action potential duration and refractory period (potassium channel inhibition) and noncompetitive α- and β-adrenergic inhibition. (toxbank.net)

Single case report indicates that methyltestosterone may impair visual function by altering serum levels and metabolism of vitamin A and beta-carotene. (interactionsguide.com)
Mitochondrion is an organelle that plays a critical role in the survival and function of cells. (fda.gov)

Industry demand for nanomaterials is growing, but metal nanoparticle toxicity is not fully understood. (go.jp)

This incident led directly to the enactment of the US Federal Food, Drug and Cosmetic Act of 1938 to mandate some animal testing[ 3 ]. (biomedcentral.com)

Together, these functions highlight the critical role of mitochondria in the life and death of cells. (fda.gov)

Anatomy15

Organisms9

Diseases11

Chemicals and Drugs118

Analytical, Diagnostic and Therapeutic Techniques and Equipment43

Phenomena and Processes58

Disciplines and Occupations4

Anthropology, Education, Sociology and Social Phenomena3

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Oxidative4

Acute liver2

Abnormal liver1

Prediction2

Mechanism6

Rarely2

Xenobiotics4

Vitro7

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Liver injury1

Occurs1

Mitochondrial4

Severe3

Chemicals2

Clinical4

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Dose1

Assessment2

Potentially1

Response3

Adverse3

Metabolite1

Protein synthesis1

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