Allyl alcohol cytotoxicity in isolated rat hepatocytes: effects of azide, fasting, and fructose.
The role of altered energy homeostasis in the lethality of allyl alcohol to isolated rat hepatocytes was studied. ATP, ADP, AMP, and viability loss (leakage of lactate dehydrogenase into the medium) were measured in isolated hepatocytes of fed or fasted rats exposed to 0.5 mM allyl alcohol. Adenine mononucleotides and cytotoxicity were determined also in hepatocytes incubated with allyl alcohol in the presence of 4 mM sodium azide or 15 mM fructose. Allyl alcohol-induced cell death in hepatocytes of fed rats was preceded by slight decreases in ATP content and energy charge (16% and 12%, respectively). More substantial decreases in these parameters occurred in parallel with cell killing, but the effect of allyl alcohol on energy status did not exceed the effect produced by a nonlethal concentration of sodium azide. Neither azide nor fructose affected the development of allyl alcohol cytotoxicity. Moreover, allyl alcohol-induced cytotoxicity was similar in hepatocytes of fed and fasted rats. The results suggest that altered energy homeostasis is a consequence rather than a cause of allyl alcohol-induced hepatocyte lethality.
Rikans
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Department of Pharmacology, College of Medicine, University of Oklahoma, Oklahoma City 73190.
Cai
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Hornbrook
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D000433:1-Propanol / Q000633:toxicity; D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D001386:Azides / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D004734:Energy Metabolism / Q000187:drug effects; D005215:Fasting; D005632:Fructose / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009153:Mutagens / Q000494:pharmacology*; D010084:Oxidation-Reduction; D020005:Propanols; D051381:Rats; D011916:Rats, Inbred F344; D019810:Sodium Azide
D000227:Adenine Nucleotides; D001386:Azides; D009153:Mutagens; D020005:Propanols; D005632:Fructose; C006463:allyl alcohol; D019810:Sodium Azide; D000433:1-Propanol; D007770:L-Lactate Dehydrogenase