Effect of acute ethanol exposure on cultured fetal rat hepatocytes: relation to mitochondrial function.
Studies from our laboratory have shown that short-term ethanol exposure inhibits epidermal growth factor-dependent replication of cultured fetal rat hepatocytes, along with a drop in ATP level, and that these effects could be caused, at least in part, by ethanol-induced oxidative stress. In these prior studies, mitochondrial morphology was abnormal and membrane lipid peroxidation products were increased, along with reduced transmembrane potential and enhanced permeability to sucrose. To define the effects of ethanol on mitochondrial function further, the present study examines the impact of ethanol exposure on mitochondrial electron transport chain components. A 24-hr exposure of cultured fetal rat hepatocytes to ethanol (2.5 mg/ml) reduced mitochondrial complex I activity by 16% (p < 0.05), complex IV by 28% (p < 0.05), and succinate dehydrogenase by 23% (p < 0.05). This reduction was paralleled by lower ADP translocase activity (24%, p < 0.05) and diminished mitochondrial glutathione (GSH) (20%, p < 0.05). Pretreatment with 0.1 mM S-adenosyl methionine, before ethanol exposure, normalized mitochondrial GSH along with activities of complex I, complex IV, and succinate dehydrogenase. A 3-hr exposure of isolated mitochondria (which do not metabolize ethanol) to ethanol (2.5 mg/ml), inhibited the activities of complex I (19%, p < 0.05), complex IV (24%, p < 0.05), and of ATP synthesis (20%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Medicine, University of Texas Health Science Center at San Antonio 78284-7878.
Henderson
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Schenker
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D000818:Animals; D002478:Cells, Cultured; D004579:Electron Transport / Q000187:drug effects* / Q000502:physiology; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D005333:Fetus; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000502:physiology; D000226:Mitochondrial ADP, ATP Translocases / Q000037:antagonists & inhibitors / Q000502:physiology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000494:pharmacology; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors / Q000502:physiology
D005609:Free Radicals; D017382:Reactive Oxygen Species; D000431:Ethanol; D012436:S-Adenosylmethionine; D000226:Mitochondrial ADP, ATP Translocases; D013385:Succinate Dehydrogenase; D016660:NAD(P)H Dehydrogenase (Quinone); D003576:Electron Transport Complex IV; D005978:Glutathione