Polychlorinated biphenylols (OH-PCBs) are potentially toxic polychlorinated biphenyl metabolites that can be eliminated by glucuronidation, catalyzed by UDP-glucuronosyltransferases (UGTs). OH-PCBs with a 3,5-dichloro-4-hydroxy substitution pattern have been detected in blood from humans and wildlife, suggesting slow elimination. In this study we assessed the glucuronidation of 4-OH-PCBs with z...

The phase I cytochrome P450 (CYP) isoenzymes have received substantial attention in the pharmacogenetic literature. Researchers are beginning to examine the role of the phase II UDP-glucuronosyltransferase (UGT) enzymes, which produce products that are more water-soluble, less toxic and more readily excreted than the parent compounds. Several reasonsmay have contributed to neglect of UGTs (comp...

Ebracteolata compound B (ECB) is one major active component of both Euphorbia ebracteolata and Euphorbia fischeriana, which have been extensively used as a tuberculocide in the Asian countries. The aim of our present study was to characterize ECB metabolism in human liver microsomes, HepG2 cells, and recombinant human enzymes. One monohydroxylation metabolite, determined by mass spectrometry to...

Two of the abundant conjugates of human nicotine metabolism result from the N-glucuronidation of S-(-)-nicotine and S-(-)-cotinine, transformations we recently demonstrated in liver microsomes. We further studied these microsomal N-glucuronidation reactions with respect to human hepatic interindividual, human intertissue, and interspecies hepatic variation. The reactivities of microsomes from h...

There is currently little information regarding the localization of UDP-glucuronosyltransferases (UGTs) in human renal cortex and medulla, and the functional contribution of renal UGTs to drug glucuronidation remains poorly defined. Using human kidney sections and human kidney cortical microsomes (HKCM) and human kidney medullary microsomes (HKMM), we combined immunohistochemistry to investigat...

mycoestrogen zearalenone (zea) is found in human foods and animal feeds. its estrogenic potencymainly depends on its biotransformation fate. the hepatic biotransformation of zea in rainbow trout wasinvestigated in this study. various concentrations of zea were separately incubated with the hepaticmicrosomal and post-mitochondrial sub-fractions in the presence of nadph, and the metabolites wered...

The COMT inhibitors entacapone and tolcapone are rapidly metabolized in vivo, mainly by glucuronidation. In this work, the main UGT isoforms responsible for their glucuronidation in vitro were characterized by using a subset of representative cloned and expressed human UGT isoforms. Entacapone in particular was seen to be an exceptionally good substrate for UGT1A9 with an even higher reaction v...

Icaritin is a naturally bioactive flavonoid with several significant effects. This study aimed to clarify the metabolite profiling, pharmacokinetics, and glucuronidation of icaritin in rats. An ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) assay was developed and validated for qualitative and quantitative analysis of icaritin. Glucuronidation rates were determ...

PURPOSE Ketoconazole has been shown to inhibit the glucuronidation of the UGT2B7 substrates zidovudine and lorazepam. Its effect on UGT1A substrates is unclear. A recent study found that coadministration of irinotecan and ketoconazole led to a significant increase in the formation of SN-38 (7-ethyl-10-hydroxycamptothecine), an UGT1A substrate. This study investigates whether ketoconazole contri...

BACKGROUND Ganoderic acid B is an important bioactive ingredient isolated from Ganoderma lucidum, and exhibits various pharmacological activities. AIMS To investigate the influence of Ganoderic acid B towards the therapeutic window of trifluoperazine (TFP). METHODS In vitro human liver microsomes (HLMs) incubation system was used to determine the inhibition of Ganoderic acid B towards the g...