Prevention of thioacetamide-induced liver necrosis by prior administration of substrates of microsomal flavin-containing monooxygenase.
Prior administration of chlorpromazine (CPZ), imipramine (IMP), mercaptoethylamine (MEA), 1-(1-naphthyl)2-thiourea (ANTU) or phenyl-thiocarbamide (PTC) but not 1,4-dithio-1-threitol (DTT), was able effectively to prevent most of thioacetamide (TAC) -induced liver necrosis. These and previous observations suggest that liver microsomal flavin-containing monooxygenase critically controls the process of activation of TAC to the ultimate necrogen.
D000081:Acetamides / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D005415:Flavins; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009336:Necrosis; D051381:Rats; D011919:Rats, Inbred Strains; D013853:Thioacetamide / Q000378:metabolism / Q000633:toxicity*
D000081:Acetamides; D005415:Flavins; D013853:Thioacetamide