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Protective Effect of Diphenyl Diselenide on Ischemia and Reperfusion-Induced Cerebral Injury: Involvement of Oxidative Stress and Pro-Inflammatory Cytokines

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Abstract

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-1β, IL-6, TNF-α and INF-γ 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 α-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.

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Acknowledgments

The financial support by UFSM, CAPES, FAPERGS/CNPq (PRONEX) #10/0005-1 and FAPERGS #1007116 research grants are gratefully acknowledged. C.A.B, G.Z. and C.W.N are recipients of CNPq fellowships.

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Correspondence to Cristina W. Nogueira.

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Brüning, C.A., Prigol, M., Luchese, C. et al. Protective Effect of Diphenyl Diselenide on Ischemia and Reperfusion-Induced Cerebral Injury: Involvement of Oxidative Stress and Pro-Inflammatory Cytokines. Neurochem Res 37, 2249–2258 (2012). https://doi.org/10.1007/s11064-012-0853-7

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