Article

CYP2E1 – Biochemical and Toxicological Aspects and Role in Alcohol-Induced Liver Injury

Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, Box 1603, New York, NY 10029, USA.
Mount Sinai Journal of Medicine A Journal of Translational and Personalized Medicine (Impact Factor: 1.62). 08/2006; 73(4):657-72. DOI: 10.1007/978-0-387-77300-1_6
Source: PubMed

ABSTRACT

Ethanol-induced oxidative stress appears to play a major role in mechanisms by which ethanol causes liver injury. Many pathways have been suggested to contribute to the ability of ethanol to induce a state of oxidative stress. One central pathway appears to be the induction of the CYP2E1 form of cytochrome P450 enzymes by ethanol. CYP2E1 is of interest because of its ability to metabolize and activate many toxicological substrates, including ethanol, to more reactive toxic products. Levels of CYP2E1 are elevated under a variety of physiological and pathophysiological conditions, and after acute and chronic alcohol treatment. CYP2E1 is also an effective generator of reactive oxygen species such as the superoxide anion radical and hydrogen peroxide, and in the presence of iron catalysts, it produces powerful oxidants such as the hydroxyl radical. This review article summarizes some of the biochemical and toxicological properties of CYP2E1, and briefly describes the use of HepG2 cell lines developed to constitutively express the human CYP2E1 in assessing the actions of CYP2E1. Regulation of CYP2E1 is quite complex and will be briefly reviewed. Future directions in research, which may help clarify the actions of CYP2E1 and its role in alcoholic liver injury, are suggested.

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    • "The present study reports the potential in vivo hepatoprotective activity of Orthosiphon diffusus against hepatic injury induced by CCl 4 in rats. Following CCl 4 hepatotoxicity, the obvious signs are the leaking of hepatocellular enzymes into the plasma thereby increasing their circulation levels (Cederbaum, 2006; Zimmerman and Seeff, 1970). Therefore, the estimation of enzymes in the circulation is a useful quantitative markers of the extent and types of hepatocellular damage (Jadon et al., 2007). "
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    Full-text · Dataset · Mar 2015
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    • "The present study reports the potential in vivo hepatoprotective activity of Orthosiphon diffusus against hepatic injury induced by CCl 4 in rats. Following CCl 4 hepatotoxicity, the obvious signs are the leaking of hepatocellular enzymes into the plasma thereby increasing their circulation levels (Cederbaum, 2006; Zimmerman and Seeff, 1970). Therefore, the estimation of enzymes in the circulation is a useful quantitative markers of the extent and types of hepatocellular damage (Jadon et al., 2007). "
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    ABSTRACT: Preparations of Orthosiphon diffusus (Benth.) have been used by folk medicinal practitioners in the Western Ghats of India for treating inflammation, hepatitis and jaundice for many years and their effectiveness is widely acclaimed among the tribal communities. To evaluate the mechanisms behind the antioxidant and hepatoprotective potential of O. diffusus methanol active fraction (MAF) using in vivo (rat) and in vitro (cell culture) models. Neutralization of CCl4-induced hepatotoxicity by MAF was evaluated in rats. Towards this, serum levels of hepatic injury markers (lactate dehydrogenase and alkaline phosphatase), antioxidant enzymes in the liver homogenates, and histological examination were performed. In in vitro studies, mechanisms of neutralization of H2O2-induced toxicity by MAF using MTT, Comet assay and up-regulation of antioxidant enzymes at genetic level (RT-PCR) was performed in HepG2 cells. Rats pre-treated with O. diffusus MAF demonstrated significantly reduced levels of serum LDH (1.3-fold, p<0.05) and ALP (1.6-fold, p<0.05). Similarly, multiple dose MAF administration demonstrated significantly enhanced levels (p<0.05) of antioxidant enzymes in the liver homogenates. Histological analysis revealed complete neutralization of CCl4-induced liver injury by the extract. The in vitro studies demonstrated that, pre-treatment of MAF effectively prevented H2O2-induced oxidative stress, genotoxicity and significantly enhanced (∼6-fold, p<0.01) expression of genes for antioxidant enzymes. O. diffusus MAF demonstrated significant hepatoprotection against CCl4-induced hepatotoxicity by antioxidant mechanisms comparable to silymarin. H2O2-induced oxidative stress was completely neutralized by MAF through enhanced expression of genes for antioxidant enzymes. Therefore, this study validates the use of O. diffusus by folk medicinal practitioners in India. Further, MAF of O. diffusus can serve as a strong candidate for the development of herbal hepatoprotective agents.
    Full-text · Article · Aug 2013 · Journal of ethnopharmacology
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    • "For personal use only. injury (Lieber, 2004; Cederbaum, 2006; Morimoto et al., 1993; Koop, 1992; Nanji et al., 1994; Knecht et al., 1995; Tsukamoto and Lu, 2001; Ronis et al., 2010). In the current experiment, we conducted an experimental model in which CYP2E1 was induced by ethanol without influence of a low-carbohydrate diet and no oxidative stress was observed. "
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    ABSTRACT: Expression of cytochrome P4502E1 (CYP2E1) is very much influenced by nutritional factors, especially carbohydrate consumption, and various results concerning the expression of CYP2E1 were obtained with a low-carbohydrate diet. This study describes the effects of ethanol treatment on CYP2E1 levels and its relationship with oxidative stress using a balanced standard diet to avoid low or high carbohydrate consumption. Rats were fed for 1, 2, 3, or 4 weeks a commercial diet plus an ethanol-sucrose solution. The results have shown that ethanol administration was associated with CYP2E1 induction and stabilization without related oxidative stress. Our findings suggest that experimental models with a low-carbohydrate/high-fat diet produce some undesirable CYP2E1 changes that are not present when a balanced standard diet is given.
    Full-text · Article · Jan 2012 · Drug and Chemical Toxicology
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