Mechanisms in 2-hexanone potentiation of chloroform hepatotoxicity.
2-Hexanone (2-Hx) is known to potentiate chloroform (CHCl3) hepatotoxicity in part by increasing the bioactivation of CHCl3 to phosgene (COCl2). Treatment of rats with 2-Hx + CHCl3 in vivo did not initiate peroxidation of hepatic fatty acids as determined by formation of conjugated dienes or depletion of unsaturated fatty acids, or as determined by production of malondialdehyde (MDA) in vitro. A 5-fold decrease in the specific activity of succinate-dependent cytochrome c reductase in liver from rats treated in vivo with corn oil (vehicle) + CHCl3 and in rats treated with 2-Hx + CHCl3 indicated that a mechanism independent of CHCl3 bioactivation may add to the hepatotoxic effects which result from the metabolism of chloroform to phosgene.
D000818:Animals; D001711:Biotransformation; D002725:Chloroform / Q000378:metabolism / Q000633:toxicity*; D004357:Drug Synergism; D007659:Ketones / Q000633:toxicity*; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects*; D008297:Male; D008742:Methyl n-Butyl Ketone / Q000633:toxicity*; D009251:NADPH-Ferrihemoprotein Reductase / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D013384:Succinate Cytochrome c Oxidoreductase / Q000032:analysis
D007659:Ketones; D008054:Lipid Peroxides; D008742:Methyl n-Butyl Ketone; D002725:Chloroform; D013384:Succinate Cytochrome c Oxidoreductase; D009251:NADPH-Ferrihemoprotein Reductase