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Hepatic mitochondrial dysfunction induced by fatty acids and ethanol.
MedLine Citation:
PMID:  23010494     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Understanding key aspects of the pathogenesis of alcoholic fatty liver disease particularly alterations to mitochondrial function remain to be resolved. The role of fatty acids in this regard requires further investigation due to their involvement in fatty liver disease and obesity. This study aimed to characterize the early effects of saturated and unsaturated fatty acids alone on liver mitochondrial function and during concomitant ethanol exposure using isolated liver mitochondria and VA-13 cells (Hep G2 cells that efficiently express alcohol dehydrogenase). Liver mitochondria or VA-13 cells were treated with increasing concentrations of palmitic or arachidonic acid (1 to 160μM) for 24h with or without 100mM ethanol. The results showed that in isolated liver mitochondria both palmitic and arachidonic acids significantly reduced state 3 respiration in a concentration dependent manner (p<0.001), implicating their ionophoric activities. Increased ROS production occurred in a dose-dependent manner especially in the presence of rotenone (complex I inhibitor), which was significantly more prominent in arachidonic acid at 80μM (+970%, p<0.001) than palmitic acid (+40%, p<0.01). In VA-13 cells, ethanol alone and both fatty acids (40μM) were able to decrease the mitochondrial membrane potential and cellular ATP levels and increase lipid formation. ROS production was significantly increased with arachidonic acid (+110%, p<0.001) exhibiting a greater effect than palmitic acid (+39%, p<0.05). Whilst in the presence of ethanol, the drop in the mitochondrial membrane potential, cellular ATP levels and increased lipid formation was further enhanced by both fatty acids, but with greater effect in the case of arachidonic acid, and which also correlated with significant cytotoxicity (p<0.001). This study confirms the ability of fatty acids to promote mitochondrial injury in the development of alcoholic fatty liver disease.
Authors:
Daniel Gyamfi; Hannah E Everitt; I Tewfik; Dahn L Clemens; Vinood B Patel
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-22
Journal Detail:
Title:  Free radical biology & medicine     Volume:  -     ISSN:  1873-4596     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Inc.
Affiliation:
Department of Biomedical Sciences, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London, W1W 6UW, UK.
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