Lipid peroxide formation and plasma membrane damage in mouse liver following the administration of Salmonella endotoxin were examined. The liver lipoperoxide level was markedly elevated in animals given endotoxin compared with that in the controls, and returned to its normal range after 2 days. On the other hand, superoxide dismutase activity was decreased by 18-48 hr after endotoxin injection, thereafter tending to increase. Glutathione reductase and glutathione peroxidase activities declined in the liver 18 hr after the injection. The endotoxin resulted in much lower lipoperoxide formation in the livers of tolerant mice than in those of the poisoned mice. The lipoperoxide level in endotoxin-poisoned mice after the administration of a-tocopherol was lower than that in the controls, and a-tocopherol administration prevented completely the membrane protein damage that arose from endotoxin challenge. After glutathione administration the membranes of the poisoned mice also returned to almost the· normal disk electrophoretic profile. These results suggest that lipid peroxide formation in the liver plasma membrane caused by free radicals might occur in a tissue ischemic state in endotoxicosis.

The effect of a-tocopherol in endotoxicosis was studied. The a-tocopherol level significantly decreased in mouse liver 18 hr after endotoxin administration, thereafter tending to increase to approach the normal range. In endotoxin-tolerant mouse liver, the lipid peroxide level was reduced to less than half of that in nontolerant animals following endotoxin challenge. The liver lipid peroxide level and serum lactate dehydrogenase or acid phosphatase leakage were studied in mice fed a vitamin E-deficient (ED) diet and a vitamin E-supplemented (ES) diet for 40 days. ED mouse liver exhibited a higher formation of lipid peroxide after endotoxin was given while there was a markedly lower level in ES mouse liver. There was significantly more serum lactate dehydrogenase or acid phosphatase leakage in ED mice than in ES mice after endotoxin administration. There was about a 25% decrease in liver superoxide dismutase (SOD) activity in endotoxin-poisoned mice fed both the normal and the ED diets, while the activity was at a higher level in ES-fed mice. These results suggest that atocopherol may be helpful in preventing membrane instability in endotoxin poisoning.In the previous paper (42), we reported that administration of Salmonella endotoxin resulted in marked formation of lipid peroxide in mouse liver compared to that in the fasting controls. On the other hand, the activities of superoxide dismutase and glutathione peroxidase, which are the scavengers of free radicals, decreased in mouse liver 18 hr postintoxication. The lipid peroxide level in endotoxinpoisoned mice given a-tocopherol, the most important form of vitamin E, was lower than that in the controls. Furthermore, it was found that a-tocopherol prevents completely the membrane protein damage which arises from endotoxin challenge.Most, if not all, of the biologically functional a-tocopherol is associated with the membranous portions of cells. Many investigators have shown that a-tocopherol plays an important antioxidant role by blocking the peroxidation of polyunsaturated fatty acid (PUFA) in biomembranes (31,43,50). Lucy proposed that a-tocopherol is intimately associated with the hydrocarbon portion of PUFAs of membranes, and may play a physicochemical role in the stabilization of biological membranes (12,26). Cook et al (9) observed that PUFA-deficient rats were significantly more resistant to bacterial endotoxic shock than normal rats, 787