Experimental and Clinical Physiology, Department of Cardiovascular Physiology, Medical University of Łódź, Mazowiecka 6/8, PL 92-215 Łódź, Poland.
Pharmacol Rep. 2013;65(1):179-86. doi: 10.1016/s1734-1140(13)70976-9.
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.
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.
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).
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.
细菌内毒素（脂多糖-LPS）是一种强烈的免疫系统调节剂，在内毒素性休克的发病机制中起着关键作用。本研究的目的是探讨硫辛酸（LA）对 LPS 诱导的内毒素性休克大鼠脾匀浆氧化应激标志物的影响。
动物在 LPS 给药前 30 分钟或后 30 分钟用盐水或硫辛酸（LA）（60 或 100mg/kg b.w.iv）处理，在 LPS 给药后 30 分钟。在 LPS 或盐水给药后 5 小时，处死动物并分离脾脏进行测量。
LPS 处理的动物发生氧化应激，表现为硫代巴比妥酸反应物质（TBARS）和过氧化氢（H2O2）浓度显著增加（p<0.001），巯基（-SH 组）水平和谷胱甘肽氧化还原比[还原型谷胱甘肽（GSH）与氧化型谷胱甘肽（GSSG）比]无明显降低（p<0.02）与对照组相比。与 LPS 组相比，LA（60 或 100mg/kg）在 LPS 给药前后给药可增加 -SH 组含量（p<0.01）并降低脾 TBARS 和 H2O2 浓度（p<0.001）。LA（60 或 100mg/kg）在 LPS 给药前降低了 GSSG 水平（p<0.05）并增加了脾匀浆中的 GSH 水平（p<0.05），与 LPS 组相比，GSH/GSSG 比值增加（p<0.01）。它还改善了 LPS 诱导的脾重（SW）与体重（BW）比的增加（p<0.001 与对照相比）。
本研究结果表明，LA 具有抗氧化特性，可防止革兰氏阴性细菌内毒素对脾脏的有害作用。
