Protective Effect of Diphenyl Diselenide on Ischemia and Reperfusion-Induced Cerebral Injury: Involvement of Oxidative Stress and Pro-Inflammatory Cytokines
Protective Effect of Diphenyl Diselenide on Ischemia and Reperfusion-Induced Cerebral Injury: Involvement of Oxidative Stress and Pro-Inflammatory Cytokines
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DOI：
10.1007/s11064-012-0853-7
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发表时间：
2012-10-01
影响因子：
4.4
通讯作者：
Nogueira, Cristina W.
中科院分区：
文献类型：
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作者：
Bruening, Cesar A.;Prigol, Marina;Nogueira, Cristina W.
脑血管疾病，包括缺血性中风，在世界范围内与高死亡率相关。氧化应激和炎症反应是缺血性脑损伤的重要病理生理机制。本研究旨在探讨具有抗氧化和抗炎作用的有机硒化合物二苯基二硒醚（PhSe）（2）对大鼠脑缺血/再灌注损伤的潜在保护作用。采用的实验模型是通过双侧颈总动脉闭塞在大鼠中进行的药物诱导的脑缺血。在缺血发作前30分钟单次口服（PhSe）（2）（50 mg/kg）的效果通过评估大鼠血浆中与脑氧化应激相关的生化参数和促炎细胞因子来研究。结果表明，脑I/R损伤引起脑组织丙二醛（MDA）、活性氧（ROS）和硝酸盐/亚硝酸盐水平的升高，以及非酶和酶（过氧化氢酶和超氧化物歧化酶）抗氧化防御系统的改变。I/R损伤后大鼠血浆IL-1 β、IL-6、TNF-α和INF-γ水平升高。（PhSe）（2）的施用恢复了暴露于I/R损伤的大鼠的脑MDA、ROS、硝酸盐/亚硝酸盐和抗氧化防御的水平。（PhSe）（2）能显著降低I/R大鼠血浆中的促炎细胞因子。I/R损伤增加了组织损伤标志物的血浆水平，如肌酸激酶和α-1-酸性糖蛋白。用（PhSe）（2）预处理可有效降低这些蛋白质的水平。此外，（PhSe）（2）可减轻I/R引起的脑组织学改变。这项研究首次显示了（PhSe）（2）对大鼠I/R损伤诱导的氧化应激和促炎细胞因子的体内保护作用。
Cerebrovascular diseases, including ischemic stroke, are associated with high mortality worldwide. Oxidative stress and inflammation are important pathophysiological mechanisms involved in post-ischemic cerebral injury. The present study was designed to investigate the potential protective effect of diphenyl diselenide (PhSe)(2), an organoselenium compound with antioxidant and anti-inflammatory properties, against ischemia/reperfusion (I/R) insult in rat brain. The experimental model adopted was that of surgically-induced brain ischemia, performed by means of bilateral common carotid artery occlusion in rats. The effect of a single oral dose of (PhSe)(2) (50 mg/kg), administered 30 min before the onset of ischemia, was investigated by assessing cerebral oxidative stress-related biochemical parameters and pro-inflammatory cytokines in plasma of rats. The results demonstrated an increase in the levels of malondialdehyde (MDA), reactive oxygen species (ROS) and nitrate/nitrite as well as the alteration in the non-enzymatic and enzymatic (catalase and superoxide dismutase) antioxidant defense system induced by I/R insult in rat brain. I/R insult increased the levels of IL-1 beta, IL-6, TNF-alpha and INF-gamma in plasma of rats. The administration of (PhSe)(2) restored cerebral levels of MDA, ROS, nitrate/nitrite and antioxidant defenses of rats exposed to I/R insult. (PhSe)(2) markedly reduced pro-inflammatory cytokines in plasma of I/R rats. I/R insult increased the plasma levels of tissue damage markers, such as creatine kinase and alpha-1-acid glycoprotein. Pretreatment with (PhSe)(2) was effective in reducing the levels of these proteins. In addition, (PhSe)(2) attenuated cerebral histological alterations induced by I/R. This study showed for the first time the in vivo protective effect of (PhSe)(2) against oxidative stress and pro-inflammatory cytokines-induced by I/R insult in rats.