department of Pharmacy,Vallabhbhai Patel Chest Institute, University of Delhi, India.
Eur J Pharmacol. 2011 Feb 10;652(1-3):55-9. doi: 10.1016/j.ejphar.2010.11.002. Epub 2010 Nov 30.
The involvement of nitric oxide (NO) in the effects of dehydroepiandrosterone sulphate (DHEAS) on restraint stress induced neurobehavioral and brain oxidative/nitrosative stress markers was investigated in rats. Exposure of rats to restraint stress suppressed behavioral activity in the elevated plus maze and this was associated with increases in malondialdehyde (MDA) and decrease in reduced glutathione (GSH) and brain NO metabolite (NOx) levels in brain homogenates. Pretreatment with DHEAS (5-40mg/s.c.) reversed the stress induced changes in behavioral and oxidative stress markers and also brain NOx levels. The beneficial effect of DHEAS (40mg/kgs.c.) was blocked by pretreatment with nitric oxide synthase inhibitor, L-NAME (50mg/kgi.p.) while pretreatment of rats with NO-precursor l-Arginine (100mg/kg i.p.) produced potentiation of action of sub effective dose of DHEAS (5mg/kgs.c.). The DHEAS effects were stress specific as these behavioral and biochemical parameters were not much influenced in non-stressed rats. These observations suggest that pretreatment with DHEAS has a protective effect on restraint stress induced alteration of neurobehavioral changes and brain oxidative injury in rats and NO-dependent mechanisms may be involved in this effect.
研究了一氧化氮（NO）在脱氢表雄酮硫酸盐（DHEAS）对束缚应激诱导的神经行为和大脑氧化/硝化应激标志物的影响。将大鼠暴露于束缚应激中会抑制高架十字迷宫中的行为活动，这与大脑匀浆中丙二醛（MDA）增加和还原型谷胱甘肽（GSH）减少以及脑 NO 代谢物（NOx）水平降低有关。DHEAS（5-40mg/s.c.）预处理可逆转应激诱导的行为和氧化应激标志物以及脑 NOx 水平的变化。DHEAS（40mg/kg，s.c.）的有益作用被一氧化氮合酶抑制剂 L-NAME（50mg/kg，i.p.）预处理所阻断，而预先给予大鼠 NO 前体 l-精氨酸（100mg/kg，i.p.）可增强 DHEAS（5mg/kg，s.c.）的亚有效剂量的作用。DHEAS 的作用是应激特异性的，因为这些行为和生化参数在非应激大鼠中没有受到太大影响。这些观察结果表明，DHEAS 预处理对束缚应激诱导的大鼠神经行为变化和大脑氧化损伤具有保护作用，并且可能涉及 NO 依赖性机制。
