Experimental alcohol-induced hepatic necrosis: suppression by propylthiouracil.
We have previously reported that a hypermetabolic state, resembling that produced by thryoid hormones, exists in the livers of animals treated chronically with ethanol. We propose that this alteration produces a relative hypoxia in the centrilobular zone of the liver which, if severe enough, leads to cellular death and to the production of hepatitis. Rats consuming ethanol for 30 days, given with a nutritionally adequate diet, and exposed to reduced oxygen tensions for only 6 hr, developed histological and biochemical evidence of hepatocellular necrosis and inflammatory lesions confined to the centrilobular zone. The severity was proportional to the degree of hypoxia. Pair-fed (nonalcohol) controls showed no such lesions. Treatment of the animals with propylthiouracil for 3-10 days abolished the hypermetabolic state of the liver in ethanol-consuming animals, and drastically reduced the histological and biochemical effects of hypoxia in them. These findings may have implications for pathogenesis and treatment of alcoholic hepatitis in man.
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D000431:Ethanol / Q000633:toxicity*; D000860:Hypoxia / Q000150:complications / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D009336:Necrosis; D010101:Oxygen Consumption; D011441:Propylthiouracil / Q000627:therapeutic use*; D051381:Rats
D000431:Ethanol; D011441:Propylthiouracil