Aged mice are resistant to the hepatotoxic effects of endotoxin and galactosamine

The ability of concurrent intraperitoneal injections of endotoxin (0.1 micrograms/kg) and galactosamine (700 mg/kg) to produce liver damage was determined in fasted C57Bl/6 mice of different ages: 2 months (young), 6 months (mature), and 24 months (aged). Liver damage was assessed after 6 hr by measurement of plasma alanine aminotransferase activity (ALAT, mumole/liter/min) and by histological examination for mature and aged mice. Control mice, those treated with saline, galactosamine, endotoxin, or hydrazine alone, had ALAT activities which ranged from 13 to 72 (n = 21). Plasma ALAT activities were increased to hepatotoxic values in some, but not all, mice injected with both endotoxin and galactosamine. For young mice, 7/11 had increased plasma ALAT activities; for mature mice, 5/8 had increased plasma ALAT activities and substantial centrilobular necrosis, whereas for aged mice, 0/7 had increased ALAT activities and none had centrilobular necrosis. Basophilic staining of the cytoplasm was increased by administration of endotoxin and/or galactosamine in both mature and aged mice whether or not necrosis was present. A 5-hr pretreatment with hydrazine sulfate (80 mg/kg) substantially decreased the ALAT release caused by endotoxin and galactosamine in mature mice. Hydrazine pretreatment prevented centrilobular necrosis in mature mice and decreased basophilic cytoplasmic staining in aged mice. The results demonstrate that aged mice are resistant to the hepatotoxic effects of endotoxin and galactosamine which were observed in both young mice and mature mice. Also, hydrazine sulfate pretreatment will protect against the hepatotoxic effects as well as the lethal actions of endotoxin and galactosamine.