Hepatic mitochondrial function and lysosomal enzyme activity in ethanol-potentiated aflatoxin B1 hepatotoxicity.
The possible role of hepatic mitochondrial function and lysosomal enzyme activity in ethanol-enhanced aflatoxin B1 (AFB1) hepatotoxicity was studied in male rats. Hepatic ATP content was significantly decreased in rats treated with ethanol (4.0 g/kg body wt.) and AFB1 (2.0 mg/kg body wt.) compared with rats treated with AFB1 alone at 12-72 h after AFB1 administration. The decrease in hepatic ATP content was due to the decrease in the activity of NADH-cytochrome c reductase whereas cytochrome oxidase activity did not differ in rats treated with ethanol and AFB1 when compared to AFB1 alone. Total and free activities of hepatic lysosomal enzymes (glucuronidase, arylsulfatase and acid phosphatase) were significantly increased in rats treated with ethanol and AFB1 at 24-36 h after AFB1 administration when compared to AFB1 alone. The increase in hepatic lysosomal enzyme activities correlated well with the increase in the lipid peroxide level of lysosomes in rats treated with ethanol and AFB1. These findings indicate that the decrease in hepatic mitochondrial respiratory enzyme activities and the increase in lipid peroxide level of lysosomes might lead to a decrease in hepatic ATP content, and that the increase in the activities of hepatic lysosomal enzymes, respectively, enhance the AFB1 hepatotoxicity of ethanol.
Toskulkao
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C
Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Glinsukon
T
T
D000135:Acid Phosphatase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D016604:Aflatoxin B1; D000348:Aflatoxins / Q000633:toxicity*; D000818:Animals; D001192:Arylsulfatases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005966:Glucuronidase / Q000378:metabolism; D008054:Lipid Peroxides / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000502:physiology; D009251:NADPH-Ferrihemoprotein Reductase / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000348:Aflatoxins; D008054:Lipid Peroxides; D000431:Ethanol; D000255:Adenosine Triphosphate; D016604:Aflatoxin B1; D009251:NADPH-Ferrihemoprotein Reductase; D003576:Electron Transport Complex IV; D000135:Acid Phosphatase; D001192:Arylsulfatases; D005966:Glucuronidase