The effect of ethanol, ethanol metabolizing enzyme inhibitors, and Vitamin E on regulating glutathione, glutathione S-transferase, and S-adenosylmethionine in mouse primary hepatocyte.

The effect of ethanol, ethanol metabolizing enzyme inhibitors, and Vitamin E on regulating glutathione, glutathione S-transferase, and S-adenosylmethionine in mouse primary hepatocyte. Research Abstract Details 

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The effect of ethanol, ethanol metabolizing enzyme inhibitors, and Vitamin E on regulating glutathione, glutathione S-transferase, and S-adenosylmethionine in mouse primary hepatocyte. Abstract Text:

Maxwell Afari Gyamfi,Yu-Jui Yvonne Wan,

We studied changes in the antioxidant systems involved in hepatoprotection after ethanol exposure in primary culture of mouse hepatocytes. Ethanol decreased glutathione (GSH) levels and the S-adenosylmethionine (SAMe) to S-adenosylhomocysteine (SAH) ratio by 53% and 22%, respectively. Cytosolic glutathione S-transferase (GST) activity was significantly lower in ethanol exposed hepatocytes, which was accompanied by an increase in GST activity in the culture medium. When specific substrates for mu- and pi-class GST were utilized, ethanol significantly decreased the mu- and pi-class GST activity by 53% and 13%, respectively. Lipid peroxidation (LPO), assessed by the thiobarbituric acid assay, increased to 221% of control by ethanol and was potentiated by cyanamide, an aldehyde dehydrogenase inhibitor. The changes in LPO, cytosolic GST activity, GSH levels and SAMe/SAH ratio in ethanol exposed hepatocytes were completely or partially reversed by either Vitamin E or 4-methylpyrazole, an alcohol dehydrogenase (ADH) inhibitor. Retinoid X receptor alpha-deficient (RXRalpha KO) mice, which are more susceptible to ethanol-induced liver toxicity, have decreased pi-class GST (56%), mu-class GST (28%), and glutathione peroxidase (35%) activities compared with wild type. Taken together, primary hepatocyte provides a valuable model to analyze ethanol-induced oxidative stress. The inhibition of mu-class GST activity by ethanol and the decreased pi-class GST activity in RXRalpha KO mice implicate the importance of these isozymes in ethanol detoxification process.

The effect of ethanol, ethanol metabolizing enzyme inhibitors, and Vitamin E on regulating glutathione, glutathione S-transferase, and S-adenosylmethionine in mouse primary hepatocyte. Publishing Authors By Initials

MA Gyamfi,YJ Wan,

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The effect of ethanol, ethanol metabolizing enzyme inhibitors, and Vitamin E on regulating glutathione, glutathione S-transferase, and S-adenosylmethionine in mouse primary hepatocyte. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Hepatology research : the official journal of the

VOLUME: 35

Page Numbers: 53-61

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ISSN: 1386-6346

DAY: 15

MONTH: 03

YEAR: 2006

The effect of ethanol, ethanol metabolizing enzyme inhibitors, and Vitamin E on regulating glutathione, glutathione S-transferase, and S-adenosylmethionine in mouse primary hepatocyte. Information

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LANGUAGE: eng

NlmUniqueID: 9711801

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AFFILIATION: University of Kansas Medical Center, Department of Pharmacology, Toxicology, and Therapeutics, Kansas City, KS 66160, United States.

Country: Netherlands

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MEDLINETA: Hepatol Res

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