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For phase 1 oxidation, phosphogyltransferase-mediated sulfation, 3'-phosphoruse mediated sulfation, with phosphoglicoratin mediated sulfation, see fig. 1; assay was carried out in the presence and absence of cofactors associated with key drug metabolism pathways known to play important roles in drug metabolism: glutathione 5'-phosphate mediated glucuronidation, By PAPS for acetaminophen, ketoconazole, and troglitazone, and troglitazone for all six medications, attenuation of cytotoxicity by UDPGA was detected for acetaminophen, ketoconazole, and troglitazone. GSH detoxification, which is a key feature of drugs with idiosyncratic hepatotoxicity, is a turning point for the discovery of cytotoxic reactive metabolites. a STATEMENT OF SIGNIFICANCE: The application of the metabolism-dependent cytotoxicity assay for the elucidation of drug metabolism and detoxification pathways in drug toxicity may help to define drug structure optimization in drug discovery in order to minimize hepatotoxic risk and aid in the identification of metabolic risk factors.
Source link: https://doi.org/10.1124/dmd.121.000645
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