Studies on the mechanism of alloxan-diabetes potentiation of carbon tetrachloride-induced liver necrosis.
Carbon tetrachloride (CCl4)-induced liver necrosis in alloxan diabetic rats is markedly more intense than in controls as established by determination of isocitric dehydrogenase activity in plasma or by histological techniques. The covalent binding (CB) of CCl4 reactive metabolites to liver microsomal lipids is higher in alloxan diabetic rats than in controls. Cytochrome c reductase activity remains unchanged in alloxan diabetic rats. All the alterations described above observed in the diabetic animals are reverted by insulin administration. CCl4-induced lipid peroxidation of microsomal lipids, in contrast, is equally intense in controls than in alloxan diabetic animals and it is not modified by insulin treatment. Body temperature in alloxan diabetic animals treated with CCl4 is lower than in controls treated with the hepatotoxin. Results suggest that part of the enhanced necrogenic response of the liver observed in alloxan diabetic rats is due to increased CB to liver cell constituents but available evidence from the present and another work suggest that increased susceptibility of the liver from alloxan diabetic animals play a major role in the potentiation of CCl4 deleterious effects.
D000496:Alloxan / Q000378:metabolism; D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000150:complications; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy; D007328:Insulin / Q000627:therapeutic use; D008054:Lipid Peroxides / Q000096:biosynthesis; D008106:Liver Cirrhosis, Experimental / Q000209:etiology*; D008862:Microsomes, Liver / Q000201:enzymology; D009245:NADH Dehydrogenase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D008054:Lipid Peroxides; D000496:Alloxan; D009245:NADH Dehydrogenase