Interrelation between lipid peroxidation and lysosomal enzyme release in the presence of carbon tetrachloride, cumene hydroperoxide or thioacetamide.
To study the relationship between lipid peroxidation (LPO) and the release of lysosomal enzymes as markers of liver injury three compounds were chosen which evoke lipid peroxidation (cumene hydroperoxide, CHP), hepatocellular injury (thioacetamide, TAA) or both (carbon tetrachloride, CCl4). Premitochondrial supernatants of phenobarbital-induced rat liver homogenates were incubated in the presence of either agent and an NADPH-regenerating system. Then, lipid peroxidation was assessed by measurement of malondialdehyde (MDA) formation and, after centrifugation at 105 000 g, released beta-glucuronidase was measured in the supernatant. While CCl4 and CHP promoted both events in a time and concentration dependent manner, TAA did not evoke either LPO or lysosomal enzyme release. Glutathione, dithiocarb and (+)-catechin inhibited both effects. Though LPO and lysosomal enzyme release proved to be related events, no strict correlation with the hepatotoxicity was found.
D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D001555:Benzene Derivatives / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D002392:Catechin / Q000494:pharmacology; D004050:Ditiocarb / Q000494:pharmacology; D005966:Glucuronidase / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology; D008658:Inactivation, Metabolic; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D013853:Thioacetamide / Q000494:pharmacology*
D000081:Acetamides; D001555:Benzene Derivatives; D008054:Lipid Peroxides; D013853:Thioacetamide; D002392:Catechin; D004050:Ditiocarb; D002251:Carbon Tetrachloride; D006899:Mixed Function Oxygenases; D005966:Glucuronidase; D005978:Glutathione; C007164:cumene hydroperoxide