Effects of lipoic acid on spleen oxidative stress after LPS administration.

Background: Bacterial endotoxin (lipopolysaccharide - LPS) is a strong modulator of the immune system that plays a crucial role in the pathogenesis of endotoxic shock. The aim of the study was to investigate the effects of lipoic acid (LA) on oxidative stress markers in spleen homogenates obtained from LPS-induced endotoxic shock rats.

Methods: The animals were treated with saline or lipoic acid (LA) (60 or 100 mg/kg b.w. iv) 30 min before or 30 min after LPS administration (30 mg/kg b.w. iv). Five hours after LPS, LA or saline administration, the animals were euthanized and their spleens were isolated for measurements.

Results: The LPS-treated animals developed oxidative stress, indicated by a significant increase in thiobarbituric acid-reactive substances (TBARS) and hydrogen peroxide (H2O2) concentrations (p<0.001) as well as an insignificant decrease in the level of sulfhydryl groups (-SH groups) and the glutathione redox ratio [reduced glutathione (GSH) to oxidized glutathione (GSSG) ratio] (p<0.02) as compared with control group. Treatment with LA (60 or 100 mg/kg) before or after LPS administration resulted in an increase in -SH group content (p<0.01) and a decrease in TBARS and H2O2 concentration in the spleen as compared with LPS group (p<0.001). LA (60 or 100 mg/kg) before LPS administration decreased the level of GSSG (p<0.05) and increased the level of GSH in spleen homogenates (p<0.05), resulting in an increase in the GSH/GSSG ratio compared with the LPS group (p<0.01). It also improved the LPS-induced increase in the spleen weight (SW) to body weight (BW) ratio (p<0.001 vs. control).

Conclusion: The present results have shown that LA is endowed with antioxidant properties that are protective in the spleen against the deleterious actions of Gram-negative bacterial endotoxin.