PubMed1991
Hepatic dysfunction caused by oxidative stress when secondary peroxidation products were administered orally was investigated in rat. In serum at 24 hr after the administration of secondary products, the contents of lipid peroxides reached a maximum, the level of tocopherol reached a minimum, and the transaminase activities were elevated. In the liver, the lipid peroxide contents were kept high between 6 and 24 hr and tocopherol level was kept low between 15 and 48 hr after the does. Therefore, the hepatic oxidative stress was most severe around 15 hr after the dose. Dysfunction in the liver having oxidative stress was then made clear. One was a disturbance in synthetic system of glucose 6-phosphate. The decreases in activities of phosphoglucomutase and glucokinase reduced a level of glucose 6-phosphate, which suppressed the supply of NADPH in pentose cycle, while the NADPH was consuming well for detoxification of endogenous lipid peroxides. Another was specific inactivations of mitochondrial succinate dehydrogenase and aldehyde dehydrogenase. A third was the depletion of CoASH, which induced the decreases in activities of citrate cycle and lipogenesis. The other was a formation of lipofuscin. Even after the liver was recovering from the oxidative stress, the liver was getting hypertrophy and lipofuscin was accumulating. To make the cause of hepatic dysfunction clear, it was examined whether the incorporated secondary products in the liver could directly attack the enzymes or not. A reasonable amount of secondary products present in the liver was estimated, and then the amount of secondary products was added in hepatic subcellular organelles in vitro. It was found that mitochondrial NAD-dependent aldehyde dehydrogenase, glucokinase, and CoASH were directly attacked and inactivated by the incorporated secondary products in the liver. Thus, a part of dietary secondary products was incorporated into liver, and was not detoxified, but injured the enzymes and CoASH. Then it resulted in lipofuscin formation.