Organisms have metabolic pathways that are responsible for removing toxic agents. We always associate the liver as the major organ responsible for detoxification of the body; however this process occurs in many tissues. In the same way, as in the liver, the brain expresses metabolic pathways associated with the elimination of xenobiotics. Besides the detoxifying role of CYP2E1 for compounds suc...

Whereas the liver as well as the other organs are continually exposed to the change of osmotic status, it has never been investigated whether activities and gene expressions of drug-metabolizing enzymes, including cytochromes P450, are dependent on osmotic change in the liver. In the present study, we determined that CYP2E1 is induced under hypertonic environments at a transcriptional level in ...

Human cytochrome P450 2E1 (CYP2E1) catalyzes themetabolism of numerous xenobiotics, including acetaminophen and ethanol. CYP2E1 expression is known to be extensively regulated by posttranscriptional and post-translational mechanisms. A previous study had reported that a single-nucleotide polymorphism (SNP) 1561A>G in the 39-untranslated region (39-UTR) of CYP2E1 leads to a decreased CYP2E1 mRNA...

Hepatic CYP2E1 is induced in several models of alcohol administration, but clinically relevant pathology is only observed in rats in a model involving the continuous intragastric administration of an ethanol-containing, corn oil-based, high-fat diet. The level of CYP2E1 correlates with the degree of liver pathology in the intragastric feeding model, which leads to the hypothesis that radical pr...

Sodium salicylate and acetylsalicylic acid are drugs used as anti-inflammatory agents. Salicylate prevents nuclear factor-kappa B activation and can cause apoptosis. However, salicylate, a substrate of CYP2E1, is also an antioxidant and can scavenge reactive oxygen species. Experiments were carried out to evaluate whether salicylate can modulate CYP2E1-dependent toxicity. Addition of a polyunsa...

Hepatofibrosis, which leads to cirrhosis and eventual hepatocellular carcinoma, is a common response to chronic toxin-mediated liver injury. Nitrosamines are potent hepatotoxic agents that cause necrosis and subsequent fibrosis in the liver as a result of cytochrome P450 2E1 (CYP2E1)-dependent metabolism, which generates toxic metabolites that form adducts with nucleic acids, leading to hepatot...

The hypothesis that N-acetyl-m-aminophenol (AMAP), the meta isomer of acetaminophen, will covalently bind to and inhibit human CYP2E1 in a timeand NADPH-dependent manner was investigated. Liquid chromatography/electrospray ionization-mass spectrometry analysis indicated that AMAP metabolites (i.e., AMAP*) selectively and covalently modified CYP2E1 apoprotein in a ratio of 1.4:1 (AMAP*/CYP2E1) i...

The hypothesis that N-acetyl-m-aminophenol (AMAP), the meta isomer of acetaminophen, will covalently bind to and inhibit human CYP2E1 in a timeand NADPH-dependent manner was investigated. Liquid chromatography/electrospray ionization-mass spectrometry analysis indicated that AMAP metabolites (i.e., AMAP*) selectively and covalently modified CYP2E1 apoprotein in a ratio of 1.4:1 (AMAP*/CYP2E1) i...

CYP2E1 metabolizes many low-molecular weight toxins and carcinogens. Some in vitro experiments suggest that CYP2E1 may be involved in the metabolic activation of diethylnitrosamine. However, there has been no direct evidence demonstrating a role for CYP2E1 in diethylnitrosamine-mediated carcinogenesis in vivo. To clarify this, we carried out a diethylnitrosamine-induced hepatocarcinogenesis exp...

CYP2E1 is of paramount toxicological significance because it metabolically activates a large number of low-molecular-weight toxicants and carcinogens. In this context, factors that interfere with Cyp2e1 regulation may critically affect xenobiotic toxicity and carcinogenicity. The aim of this study was to investigate the role of female steroid hormones in the regulation of CYP2E1, as estrogens a...