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Alcohol depletes coenzyme-Q(10) associated with increased TNF-alpha secretion to induce cytotoxicity in HepG2 cells.
MedLine Citation:
PMID:  22841563     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Alcohol consumption has been implicated to cause severe hepatic steatosis which is mediated by alcohol dehydrogenase (ADH) activity and CYP(450) 2E1 expression. In this context, the effect of ethanol was studied for its influence on lipogenesis in HepG2 cell which is deficient of ADH and does not express CYP(450) 2E1. The results showed that ethanol at 100mM concentration caused 40% cytotoxicity at 72h as determined by MTT assay. The incorporation of labeled [2-(14)C] acetate into triacylglycerol and phospholipid was increased by 40% and 26% respectively upon 24h incubation, whereas incorporation of labeled [2-(14)C] acetate into cholesterol was not significantly increased. Further, ethanol inhibited HMG-CoA reductase which is a rate-limiting enzyme in the cholesterol biosynthesis. It was observed that, HMG-CoA reductase inhibition was brought about by ethanol as a consequence of decreased cell viability, since incubation of HepG2 cells with mevalonate could not increase the cholesterol content and increase the cell viability. Addition of ethanol significantly increased TNF-alpha secretion and depleted mitochondrial coenzyme-Q(10) which is detrimental for cell viability. But vitamin E (10mM) could partially restore coenzyme-Q(10) and glutathione content with decreased TNF-alpha secretion in ethanol treated cells. Further, lipid peroxidation, glutathione peroxidase and superoxide dismutase enzyme activities remained unaffected. Ethanol decreased glutathione content while, GSH/GSSG ratio was significantly higher compared to other groups showing cellular pro-oxidant and antioxidant balance remained intact. Alanine amino transferase activity was increased by 4.85 folds in cells treated with ethanol confirming hepatocyte damage. Hence, it is inferred that ethanol induced cytotoxicity in HepG2 cells due to coenzyme-Q(10) depletion and increased TNF-alpha secretion.
Authors:
Satyakumar Vidyashankar; Krishna S Nandakumar; Pralhad S Patki
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-24
Journal Detail:
Title:  Toxicology     Volume:  -     ISSN:  1879-3185     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Ireland Ltd.
Affiliation:
Cell Biology and Biochemistry, Research and Development, The Himalaya Drug Company, Makali, Bangalore - 562 123, India.
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