Sugino K, Dohi K, Yamada K, Kawasaki T
Department of Biochemistry, Hiroshima University School of Medicine, Japan.
Surgery. 1989 Feb;105(2 Pt 1):200-6.
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.
革兰氏阴性菌内毒素（脂多糖）可通过脂质过氧化作用诱导小鼠肝脏损伤，而给予抗氧化剂（辅酶Q10和α-生育酚）可抑制这种脂质过氧化作用，维持能量代谢，并提高内毒素处理小鼠的存活率。因此，开展了实验以确定小鼠实验性内毒素血症是否会影响内源性抗氧化剂水平，以及抗氧化剂治疗是否会改变这些水平。随着时间推移，内毒素会使肝脏内源性抗氧化剂减少：给予内毒素24小时后，还原型辅酶Q9、α-生育酚和还原型谷胱甘肽分别降至对照水平的29.9%、27.1%和45.4%。外源性给予的辅酶Q10（氧化型）在肝脏中蓄积，在注射后8至16小时达到最大平台期，此时82%的辅酶Q10转化为还原型。与内毒素一起给予的辅酶Q10完全或部分阻止了这些内源性抗氧化剂的减少，此外，在脂质过氧化作用升高的时期（内毒素注射后16小时），总辅酶Q10和还原型辅酶Q10在蛋白质水平约为30毫克时均被消耗。这些结果表明，辅酶Q10在体内转化为还原型后可作为抗氧化剂发挥作用。给予的α-生育酚在注射后8小时肝脏中也显示出84倍的蓄积，完全阻止了内源性还原型辅酶Q9的任何减少，并部分阻止了谷胱甘肽的减少，这表明α-生育酚在体内具有抗氧化作用。这些结果支持了以下假设：给予的辅酶Q10或α-生育酚与内源性抗氧化剂协同发挥作用，以防止内毒素血症中脂质过氧化引起的组织损伤。
