Cytochrome P450 2E1: its clinical and toxicological role

Tanaka, Einosuke; Terada, Masaru; Misawa, Shogo

doi:10.1046/j.1365-2710.2000.00282.x

Cited by 182 publications

(155 citation statements)

References 83 publications

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“…CYP2E1 metabolizes a variety of small, hydrophobic substrates and drugs (reviewed in 40,[43][44][45][46]. Possible physiological substrates are acetone and fatty acids such as linoleic and arachidonic acid (47).…”

Section: Cyp2e1 Substratesmentioning

confidence: 99%

CYP2E1 and oxidative liver injury by alcohol

Cederbaum

2008

Free Radical Biology and Medicine

641

534

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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 cytochrome P450 2E1 (CYP2E1) by ethanol. CYP2E1 metabolizes and activates 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, 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 cell lines developed to constitutively express CYP2E1 in assessing the actions of CYP2E1. Possible therapeutic implications for treatment of alcoholic liver injury by inhibition of CYP2E1 or CYP2E1-dependent oxidative stress will be discussed, followed by some future directions which may help to understand the actions of CYP2E1 and its role in alcoholic liver injury.

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Section: Cyp2e1 Substratesmentioning

confidence: 99%

CYP2E1 and oxidative liver injury by alcohol

Cederbaum

2008

Free Radical Biology and Medicine

641

534

View full text Add to dashboard Cite

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“…As one of the key alcohol-metabolizing enzymes induced by ethanol, CYP2E1 accounts for the metabolic activation of carcinogenic N-nitrosamines, polycyclic aromatic hydrocarbons and other low-molecular weight compounds (Lai and Shields, 1999). In addition, various halogenated anesthetics and drugs were identified as substrates for CYP2E1 (Tanaka et al, 2000). Thus, the CYP2E1 gene could play an important role of human susceptibility to liver cancer under various exogenous factors.…”

Section: Cyp2e1 Rsai/psti Polymorphism and Liver Cancer Risk Among Eamentioning

confidence: 99%

CYP2E1 RsaI/PstI Polymorphism and Liver Cancer Risk among East Asians: a Huge Review and Meta-analysis

Tian

Li²,

Zhao³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Published data on any association between the CYP2E1 RsaI/PstI (c1/c2) polymorphism and liver cancer risk among east Asians are inconclusive. The aim of this Human Genome Epidemiology (HuGE) review and metaanalysis was to derive a more precise estimation of the relationship. A literature search of Pubmed, Embase, Web of science and CBM databases from inception through July 2012 was conducted. Twelve case-control studies were included with a total of 1,552 liver cancer cases and 1,763 healthy controls. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association under five genetic models. When all the eligible studies were pooled into the meta-analysis, the results showed that the c2 allele and the c2 carrier (c2/c2 + c2/c1) of RsaI/PstI polymorphism were associated with decreased risk of liver cancer among east Asians (

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“…In chronic situations, the ADH pathway of ethanol metabolism switches to the pathway involving MEOS and CYP2E1 (14). The activation of CYP2E1 by ethanol is one of the main metabolic ethanol pathways and is responsible for the production of oxidative damage in hepatocytes (15).…”

Section: Free Form Bound Form Total ---------------------------------mentioning

confidence: 99%

The sap of Acer okamotoanum decreases serum alcohol levels after acute ethanol ingestion in rats

Yoo

Jung²,

Kang³

et al. 2011

Int J Mol Med

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Abstract. In the present study, we examined whether Acer okamotoanum (A. okamotoanum) sap decreased the serum alcohol and acetaldehyde levels after acute ethanol treatment in a rat model. Male rats were orally administered 25, 50 or 100% A. okamotoanum sap 30 min prior to oral challenge with 3 ml of ethanol (15 ml/kg of a 20% ethanol solution in water), and the blood concentrations of alcohol and acetaldehyde were analyzed up to 7 h after the treatment. Pre-treatment with the sap significantly decreased the blood ethanol and acetaldehyde concentrations after 5 h when compared with ethanol treatment alone (a negative control). The expression levels of liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) mRNA were increased significantly in animals pre-treated with A. okamotoanum sap when compared with negative and positive controls. The data suggest that sap pretreatment enhanced the alcohol metabolism rate in the rat liver. To investigate the involvement of mitochondrial regulation in the ethanol-induced hepatocyte apoptosis, we carried out an immunohistochemical analysis of Bax and Bcl-2. Pre-treatment with sap significantly decreased Bax expression and increased Bcl-2 expression 7 h after ethanol administration when compared with the negative control. The data suggest that A. okamotoanum sap pre-treatment may reduce the alcohol-induced oxidative stress in the rat liver.

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Cytochrome P450 2E1: its clinical and toxicological role

Cited by 182 publications

References 83 publications

CYP2E1 and oxidative liver injury by alcohol

CYP2E1 and oxidative liver injury by alcohol

CYP2E1 RsaI/PstI Polymorphism and Liver Cancer Risk among East Asians: a Huge Review and Meta-analysis

The sap of Acer okamotoanum decreases serum alcohol levels after acute ethanol ingestion in rats

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