Elevated glutathione level does not protect against chronic alcohol mediated apoptosis in recombinant human hepatoma cell line VL-17A over-expressing alcohol metabolizing enzymes - Alcohol dehydrogenase and Cytochrome P450 2E1

Karthikeyan Chandrasekaran, Kavitha Swaminathan, S. Mathan Kumar, Suvro Chatterjee, Dahn L. Clemens, Aparajita Dey

Research output: Contribution to journalArticle

7 Scopus citations


Chronic consumption of alcohol leads to liver injury. Ethanol-inducible Cytochrome P450 2E1 (CYP2E1) plays a critical role in alcohol mediated oxidative stress due to its ability to metabolize ethanol. In the present study, using the recombinant human hepatoma cell line VL-17A that over-expresses the alcohol metabolizing enzymes - alcohol dehydrogenase (ADH) and CYP2E1; and control HepG2 cells, the mechanism and mode of cell death due to chronic ethanol exposure were studied. Untreated VL-17A cells exhibited apoptosis and oxidative stress when compared with untreated HepG2 cells. Chronic alcohol exposure, i.e., 100. mM ethanol treatment for 72. h caused a significant decrease in viability (47%) in VL-17A cells but not in HepG2 cells. Chronic ethanol mediated cell death in VL-17A cells was predominantly apoptotic, with increased oxidative stress as the underlying mechanism. Chronic ethanol exposure of VL-17A cells resulted in 1.1- to 2.5-fold increased levels of ADH and CYP2E1. Interestingly, the level of the antioxidant GSH was found to be 3-fold upregulated in VL-17A cells treated with ethanol, which may be a metabolic adaptation to the persistent and over-whelming oxidative stress. In conclusion, the increased GSH level may not be sufficient enough to protect VL-17A cells from chronic alcohol mediated oxidative stress and resultant apoptosis.

Original languageEnglish (US)
Pages (from-to)969-978
Number of pages10
JournalToxicology in Vitro
Issue number4
StatePublished - Jun 1 2011



  • ADH
  • Apoptosis
  • CYP2E1
  • Chronic alcohol
  • GSH
  • Liver

ASJC Scopus subject areas

  • Toxicology

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