Effect of thioperamide on oxidative stress markers in middle cerebral artery occlusion model of focal cerebral ischemia in rats
Effect of thioperamide on oxidative stress markers in middle cerebral artery occlusion model of focal cerebral ischemia in rats
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DOI：
10.1177/0960327108094608
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发表时间：
2008-10-01
影响因子：
2.8
通讯作者：
Vohora, D.
中科院分区：
文献类型：
--
作者：
Akhtar, M.;Pillai, K. K.;Vohora, D.
鉴于最近有证据表明组胺参与脑缺血，本研究评估了选择性组胺 H-3 受体拮抗剂硫哌丁胺 (THP) 对大脑中动脉闭塞 (MCAO) 引起的大鼠局灶性脑缺血的作用。对大鼠进行 2 小时的 MCAO，然后再灌注 22 小时，然后评估握力、运动活动和自发交替性能。然后杀死动物并评估整个大脑中的氧化应激标记物。 MCAO 后观察到硫代巴比妥酸反应物质 (TBARS) 升高，谷胱甘肽 (GSH) 和抗氧化酶（如谷胱甘肽-S-转移酶 (GST)、谷胱甘肽过氧化物酶 (GPx)、谷胱甘肽还原酶 (GR) 和超氧化物歧化酶 (SOD)）减少，后两者在统计学上不显着。 THP（5.5 mg/kg i.p. 和 11 mg/kg i.p.）预处理显着逆转了 MCAO 诱导的 TBARS 增加，但无法逆转其他参数。矛盾的是，它进一步降低了 GPx、GR 和 SOD 的水平。大鼠的过氧化氢酶水平、握力和自发交替行为没有观察到显着变化。运动活性略有降低，但在 THP 预处理后出现逆转。 THP 对氧化应激的双重作用需要进一步研究，并对其在脑缺血中的可能用途提出质疑。
In view of the recent evidence for the involvement of histamine in cerebral ischemia, the present study evaluated the effect of thioperamide (THP), a selective histamine H-3-receptor antagonist, on middle cerebral artery occlusion (MCAO) induced focal cerebral ischemia in rats. The rats were subjected to 2 h of MCAO followed by 22 h reperfusion after which the grip strength, locomotor activity and spontaneous alternation performance were assessed. Animals were then killed and oxidative stress markers were estimated in the whole brain. An elevation of thiobarbituric acid reactive substance (TBARS) and a reduction in glutathione (GSH) and antioxidant enzymes, such as glutathione-S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR) and superoxide dismutase (SOD), was observed following MCAO, the last two being statistically insignificant. Pretreatment with THP (5.5 mg/kg i.p. and 11 mg/kg i.p.) significantly reversed the MCAO-induced increase in TBARS, but could not reverse the other parameters. Paradoxically, it further reduced the levels of GPx, GR and SOD. No significant changes were observed in the catalase levels and in the grip strength and spontaneous alternation behavior of rats. Locomotor activity was reduced slightly, but reversed on pretreatment with THP. The dual effect of THP on oxidative stress requires further investigation and raises doubts on its possible use in cerebral ischemia.