Oxidant stress and hepatic necrosis in rats treated with diquat.
Although diquat produces massive oxidant stress in both Fischer and Sprague-Dawley rats, the Fischer rats sustain hepatic necrosis and the Sprague-Dawley rats do not. A previous example of probable hepatic necrosis produced by an oxidant stress-generating compound was demonstrated in animals in which glutathione peroxidase activity had been decreased by a dietary deficiency of selenium. In the present study the susceptible Fischer rats had hepatic peroxidase activities equal to the resistant Sprague-Dawley rats. Hepatotoxic doses of diquat did not diminish hepatic glutathione peroxidase or reductase activities or hepatic content of ascorbic acid, NADPH or protein sulfhydryls. Hepatic nonprotein sulfhydryls were decreased by 50% but recovered to control values by 6 h. Biliary excretion of oxidized glutathione in the Fischer rat after administration of diquat was 4 times that observed after administration in Sprague-Dawley rats. The diquat-induced peroxidation of hepatic lipids was indicated by small increases in the 11-, 12-, and 15-hydroxyeicosatetraenoic acids, as quantitated by a new gas chromatography-mass spectrometry assay. Thus, acute lethal injury caused by redox cycling compounds that generate reactive oxygen species does not exhibit a number of the biochemical alterations in vivo that occur with cell death produced by similar compounds in isolated hepatocyte systems.
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000097:blood; D004178:Diquat / Q000494:pharmacology*; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D019803:Glutathione Disulfide; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006880:Hydroxy Acids / Q000378:metabolism; D008099:Liver / Q000473:pathology*; D008297:Male; D009249:NADP / Q000378:metabolism; D009336:Necrosis; D011726:Pyridinium Compounds / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D013312:Stress, Physiological / Q000473:pathology*
D006880:Hydroxy Acids; D011726:Pyridinium Compounds; D009249:NADP; D004178:Diquat; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; D001205:Ascorbic Acid; D019803:Glutathione Disulfide