The role of lipid peroxidation in endotoxin-induced hepatic damage and the protective effect of antioxidants

Abstract

Intraperitoneal injection of endotoxin (lipopolysaccharide, [LPS]) to mice at a dose of 15 mg/kg of body weight resulted in a survival rate of 31% 48 hours after administration. Simultaneous intramuscular administration of (10 mg/kg) coenzyme Q10 (CoQ10) increased the survival rates of LPS-administered mice to 69.7%. When LPS administration was increased to 30 mg/kg, no survivors were observed in the placebo group. Simultaneous intravenous injection of CoQ10 (10 mg/kg) or alpha-tocopherol (20 mg/kg) restored the survival rate to 52.9% or 42.9%, respectively. The adenosine triphosphate (ATP) level in the liver, which is the best index of the energy state, decreased gradually to 70% of the control ATP level 24 hours after LPS (15 mg/kg) administration. The lipid peroxide level in the liver increased fivefold 16 hours after LPS administration and then decreased to the control level in 8 hours. Simultaneous treatment of mice with antioxidants, such as CoQ10 or alpha-tocopherol, completely suppressed the lipid peroxide level in the liver and preserved the hepatic ATP level in the normal range. These results indicate that LPS induced hepatic damage in mice because of lipid peroxidation and that antioxidants suppressed lipid peroxidation, preserved energy metabolism in the liver, and enhanced survival of endotoxin-administered mice.