Prophylaxis with α-lipoic acid against lipopolysaccharide-induced brain injury in rats

Lipopolysaccharide (LPS) stimulates the synthesis and release of reactive oxygen species that play an important role in the pathogenesis of tissue injuries. In this study the effect of early administration of the antioxidant alpha-lipoic acid (alpha-LA) on brain lipid peroxidation, brain hydrogen peroxide (H(2)O(2)) concentration, and brain total sulfhydryl group (-SH group) content was evaluated in rats with endotoxic shock induced by administration of LPS (Escherichia coli 026:B6, 30 mg/kg i.v.) Rats were treated intravenously with normal saline or alpha-LA (60 mg/kg) 30 min after LPS injection. After 5 h of observation, the animals were killed and their brains were isolated for the measurements. Injection of LPS alone resulted in the development of shock and oxidative stress, the latter indicated by a significant increase in brain concentrations of thiobarbituric acid-reacting substances (TBARS) and H(2)O(2) and a decrease in total brain -SH group content. Administration of alpha-LA after the LPS challenge resulted in an increase in total -SH group content and a decrease in TBARS and H(2)O(2) concentration in the brain tissue compared with the LPS group. The results indicate that alpha-LA treatment effectively protected the brain tissue against endotoxin-induced oxidative stress. Administration of LA could be a useful adjunct to clinical application in the management of septic shock.