Hepatotoxicity caused by dietary secondary products originating from lipid peroxidation
Kanazawa, K.
Advances in Experimental Medicine and Biology 289: 237-253
1991
ISSN/ISBN: 0065-2598 PMID: 1832811 Document Number: 372324
Hepatic dysfunction caused by oxidative stress when secondary peroxidation products were administered orally was investigated in male Wistar rats. 24 h after the administration the serum contents of lipid peroxides reached a maximum, those of tocopherol reached a minimum and the transaminase activities were elevated. In the liver, the lipid peroxide contents were high between 6 and 24 h and tocopherol level was low between 15 and 48 h after the dose. The hepatic oxidative stress was most severe around 15 h after the dose. Dysfunction in the liver having oxidative stress was then made clear. One was a disturbance in glucose 6-phosphate synthesis. The decreases in activities of phosphoglucomutase and glucokinase reduced glucose 6-phosphate levels, which suppressed the supply of NADPH in pentose cycle, while the NADPH was used for detoxification of endogenous lipid peroxides. Another was specific inactivation of mitochondrial succinate dehydrogenase and aldehyde dehydrogenase. A third was the depletion of CoASH, which induced decreases in the activities of citrate cycle and lipogenesis. The other was a formation of lipofuscin. Secondary products in the liver were estimated and then added to hepatic subcellular organelles in vitro. It was found that mitochondrial NAD-dependent aldehyde dehydrogenase, glucokinase and CoASH were directly inactivated by the incorporated secondary products in the liver. Thus, some dietary secondary products were incorporated into liver, not detoxified, but injured the enzymes and CoASH and resulting in lipofuscin formation.