Changes in the levels of endogenous antioxidants in the liver of mice with experimental endotoxemia and the protective effects of the antioxidants.

Gram-negative bacterial endotoxin (lipopolysaccharide) induces hepatic damage in mice caused by lipid peroxidation, and administration of antioxidants (coenzyme Q10 and alpha-tocopherol) suppresses this lipid peroxidation, preserves energy metabolism, and enhances the survival of endotoxin-administered mice. Therefore experiments were done to determine whether experimental endotoxemia in mice affected the levels of endogenous antioxidants and whether treatment with antioxidants altered these levels. Endotoxin produced decreases in hepatic endogenous antioxidants with time: reduced coenzyme Q9, alpha-tocopherol, and reduced glutathione were lowered to 29.9%, 27.1%, and 45.4% of the control levels, respectively, 24 hours after administration. Exogenously administered coenzyme Q10 (oxidized) accumulated in the liver and showed a maximal plateau between 8 and 16 hours after injection when 82% of coenzyme Q10 was converted to the reduced form. Coenzyme Q10 administered with endotoxin totally or partially prevented the decreases in these endogenous antioxidants, and furthermore, total coenzyme Q10 and the reduced form, both at levels of approximately 30 mg protein, were consumed during the period of elevated lipid peroxidation, 16 hours after endotoxin injection. These results indicate that coenzyme Q10 acts in vivo as an antioxidant after it has been converted to the reduced form. alpha-Tocopherol administered also showed an 84-fold accumulation in the liver 8 hours after injection, completely preventing any decrease in endogenous reduced coenzyme Q9 and partially preventing reduction of glutathione, which indicated an in vivo antioxidant action of alpha-tocopherol. These results support the assumption that administered coenzyme Q10 or alpha-tocopherol functions cooperatively with endogenous antioxidants to prevent tissue damage caused by lipid peroxidation in endotoxemia.