Lipoic Acid Protects the Heart from LPS Toxicity

Lipopolysaccharide (LPS) is a gram-negative bacterial endotoxin and a major factor that contributes to multiple organ failure, including heart injury. Myocardial dysfunction in septic shock depends on the presence of proinflammatory cytokines and reactive oxygen/nitrogen species. In this study, the effect of early administration of an antioxidant, alpha-lipoic acid (LA) on lipid peroxidation, hydrogen peroxide (H(2)O(2)), sulphydryl groups (-SH groups) and total protein concentration and the glutathione redox system was evaluated in the heart homogenates obtained from LPS-induced endotoxic shock rats (Escherichia coli 026:B6, 30 mg/kg, i.v.). The animals were treated intravenously with saline or LA (60 mg/kg or 100 mg/kg i.v.) 30 min after LPS injection. Five hours after LPS, LA or saline administration, the animals were sacrificed and their hearts were isolated for measurements. Injection of LPS alone resulted in the development of shock and oxidative stress that was indicated by a significant increase in thiobarbituric acid reactive substances (TBARS) and H(2)O(2) concentrations, a decrease in concentration of -SH groups and reduced glutathione, and by decrease in glutathione redox ratio reduced glutathione (GSH)/oxidized glutathione (GSSG) in the heart. Administration of LA after the LPS challenge resulted in an increase in the sulfhydryl group content and a decrease in TBARS and H(2)O(2) concentrations in the heart as compared with the LPS group. In addition, the treatment of LA after LPS challenge significantly decreased the level of GSSG, increased the level of GSH in heart homogenates resulting in an increase of the GSH/GSSG ratio compared with the LPS group. There was no difference in oxidative stress reduction between 60 mg/kg and 100 mg/kg doses. These results indicate that early administration of LA is highly effective in dampening endotoxin-induced oxidative stress in the heart and in improving the glutathione redox system. This study supports the idea that alpha-LA is a free radical scavenger and a potent antioxidant.