Damage of rat liver microsomal mixed function oxidase system by carbon tetrachloride. In vivo study with selective inhibitor of lipid peroxidation.
Pretreatment of rats with 4-[4-N-sodium-N-(5-ethyl-1-thia-3,4-diazol-2-yl)sulfophenylamin o]-5- methoxy-1,2-benzoquinone (Q) before carbon tetrachloride intoxication inhibited lipid peroxidation by 85% but did not prevent cytochrome P-450 destruction, decrease of hydroxylase activity, and loss of the capability to bioactivate carbon tetrachloride in rat liver microsomes. Also no influence of Q on 10-day lethality was found. We conclude that covalent binding of free radical products of metabolic cleavage to various cellular structures is apparently the main damage factor of carbon tetrachloride hepatotoxicity rather than lipid peroxidation.
Kostyuk
V A
VA
Department of Biology, V.I. Lenin Byelorussian State University, Minsk, USSR.
Potapovich
A I
AI
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology*; D001665:Binding Sites; D001711:Biotransformation; D002251:Carbon Tetrachloride / Q000493:pharmacokinetics / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D005609:Free Radicals; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D016227:Benzoquinones; D005609:Free Radicals; C073033:4(N-(5-ethyl-1-thia-3,4-diazol-2-yl)sulfophenylamino)-5-methoxy-1,2-benzoquinone; D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride; D006899:Mixed Function Oxygenases