BACKGROUND After living donor liver transplantation (LDLT), rising serum bilirubin levels commonly indicate insufficient numbers of hepatocytes are available to metabolize bilirubin into biliverdin. Recovery of bilirubin levels is an important marker of hepatocyte repopulation after LDLT. Cytochrome P450 (CYP) 2A6 in humans (or cyp2a4 in rodents) can function as "bilirubin oxidase." Functional ...

BACKGROUND Rifampicin-based tuberculosis (TB) treatment alters efavirenz (EFV) clearance. Polymorphisms in important drug metabolizing enzymes and the implications for EFV dosing were investigated. METHODS Trough EFV concentrations (Cmin) were measured in 54 South African black patients. During TB treatment, EFV dose was 600 mg in patients <50 kg or 800 mg if ≥50 kg. Off TB treatment it was 6...

Quinoline is a hepatocarcinogen in rats and mice and a well-known mutagen in bacteria after incubation with rat liver microsomes. The specific cytochrome P450 enzymes involved in quinoline metabolism in human and rat liver microsomes were determined using cDNA-expressed cytochrome P450s, correlations with specific cytochrome P450-linked monooxygenase activities in human liver microsomes and inh...

OBJECTIVES Efavirenz is widely prescribed for HIV-1 infection, and CYP2B6 polymorphisms 516G→T and 983T→C define efavirenz slow metabolizer genotypes. To identify genetic predictors of higher plasma efavirenz concentrations beyond these two common functional alleles, we characterized associations with mid-dosing interval efavirenz concentrations in 84 HIV-infected adults, all carrying two copie...

Tegafur (FT) is a prodrug of 5-fluorouracil (5-FU) used in cancer chemotherapy, and the bioactivation of FT to 5-FU is mainly catalyzed by cytochrome P450 (CYP) in hepatic microsomes. FT has a chiral center and is a racemate consisting of the enantiomers, R- and S-FT. In the present study, we clarified the enantioselectivity in the conversion of FT to 5-FU and identified human CYP isoforms invo...

In order to investigate the relative levels of expression of human cytochrome P-450 (P-450) CYP2A genes and determine how this relates to polymorphism in coumarin hydroxylase activity, cDNA clones for members of the CYP2A gene family were isolated. These clones were CYP2A6, CYP2A7 and an alternatively spliced version of CYP2A7 (CYP2A7AS). The latter clone was missing exon 2, but contained a 10 ...

To investigate the role of hepatic 18-carbon fatty acids (FA) accumulation in regulating CYP2A5/2A6 and the significance of Nrf2 in the process during hepatocytes steatosis, Nrf2-null, and wild type mice fed with high-fat diet (HFD), and Nrf2 silenced or over expressed HepG2 cells administered with 18-carbon FA were used. HE and Oil Red O staining were used for mice hepatic pathological examina...