Human CYP2E1 is one of the pharmacologically and toxicologically important cytochrome P450 isoforms. Earlier studies have reported that the CYP2E1 expression is extensively regulated by post-transcriptional and post-translational mechanisms, but the molecular basis remains unclear. In the present study, we examined the possibility that microRNA may be involved in the post-transcriptional regula...

The cytochrome P450 (P450) CYP2E1 enzyme metabolizes and activates a wide array of toxicological substrates, including alcohols, the widely used analgesic acetaminophen, acetone, benzene, halothane, and carcinogens such as azoxymethane and dimethylhydrazine. Most studies on the biochemical and pharmacological actions of CYP2E1 are derived from studies with rodents, rabbits, and cultured hepatoc...

Chronic ethanol consumption was previously shown to induce CYP2A5 in mice, and this induction of CYP2A5 by ethanol was CYP2E1 dependent. In this study, the mechanisms of CYP2E1-dependent ethanol induction of CYP2A5 were investigated. CYP2E1 was induced by chronic ethanol consumption to the same degree in wild-type (WT) mice and CYP2A5 knockout (Cyp2a5 (-/-)) mice, suggesting that unlike the CY...

BACKGROUND The mechanisms responsible for the initiation of alcoholic pancreatitis remain elusive. However, there is an increasing body of evidence that reactive oxygen species play a role in both acute and chronic pancreatitis. In the liver, cytochrome P4502E1 (CYP2E1, the inducible ethanol metabolising enzyme) is one of the proposed pathways by which ethanol induces oxidative stress. AIMS T...

Chlomethiazole (CMZ) is a sedative and anticonvulsant drug that has been shown to be an efficient transcriptional inhibitor of expression of rat hepatic ethanol-inducible cytochrome P-450 2E1 (CYP2E1). Recent results have shown that human CYP2E1 expression in vivo is almost completely inhibited in control subjects and in alcoholic patients treated with CMZ. In the present investigation, we eval...

Studies in microsomal and reconstituted systems have shown that the presence of one cytochrome P450 isoform can significantly influence the catalytic activity of another isoform. In this study, we assessed whether CYP2E1 could influence the catalytic activity of CYP2B4 under steady-state turnover conditions. The results show that CYP2E1 inhibits CYP2B4-mediated metabolism of benzphetamine (BNZ)...

Studies in microsomal and reconstituted systems have shown that the presence of one cytochrome P450 isoform can significantly influence the catalytic activity of another isoform. In this study, we assessed whether CYP2E1 could influence the catalytic activity of CYP2B4 under steady-state turnover conditions. The results show that CYP2E1 inhibits CYP2B4-mediatedmetabolism of benzphetamine (BNZ) ...

Acetaminophen (APAP) hepatotoxicity is mediated by N-acetyl- p -benzoquinone imine (NAPQI), a highly toxic metabolite generated cytochrome P450 2E1 (CYP2E1). Thus, pathological conditions increasing CYP2E1 activity can favour APAP-induced liver injury, which characterized massive hepatocellular necrosis and secondary sterile inflammation. In recent work, Wang et al. showed that was exacerbated ...

CYP2A5 metabolizes xenobiotics and activates hepatocarcinogens, and induction occurs in response to hepatic damage and cellular stress. We evaluated whether ethanol can elevate CYP2A5 and whether CYP2E1 plays a role in the ethanol induction of CYP2A5. Wild-type (WT), CYP2E1 knockout (KO), and CYP2E1 knockin (KI) mice were fed ethanol for 3 weeks. Ethanol increased CYP2E1 and CYP2A5 protein and ...

The state of pregnancy is known to alter hepatic drug metabolism. Hormones that rise during pregnancy are potentially responsible for the changes. Here we report the effects of prolactin (PRL), placental lactogen (PL), and growth hormone variant (GH-v) on expression of major hepatic cytochromes P450 expression and a potential molecular mechanism underlying CYP2E1 induction by PL. In female huma...