Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS CEP 97105-900, Brazil.
Neurochem Res. 2012 Oct;37(10):2249-58. doi: 10.1007/s11064-012-0853-7. Epub 2012 Jul 31.
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.
脑血管疾病，包括缺血性中风，在全球范围内与高死亡率相关。氧化应激和炎症是涉及缺血性脑损伤后病理生理机制的重要因素。本研究旨在探讨具有抗氧化和抗炎特性的二苯二硒醚（PhSe）（2）对大鼠脑缺血再灌注（I / R）损伤的潜在保护作用。采用手术诱导脑缺血的实验模型，通过双侧颈总动脉闭塞在大鼠中进行。通过评估大鼠血浆中与氧化应激相关的生化参数和促炎细胞因子来研究 50mg / kg 单剂量（PhSe）（2）（口服）在缺血发作前 30 分钟给药的效果。结果表明，I / R 损伤会导致大鼠脑内丙二醛（MDA）、活性氧（ROS）和硝酸盐/亚硝酸盐水平升高，以及非酶和酶（过氧化氢酶和超氧化物歧化酶）抗氧化防御系统改变。I / R 损伤会增加大鼠血浆中白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）的水平。（PhSe）（2）给药可恢复 I / R 损伤大鼠脑内 MDA、ROS、硝酸盐/亚硝酸盐和抗氧化防御水平。（PhSe）（2）可显著降低 I / R 大鼠血浆中的促炎细胞因子。I / R 损伤会增加肌酸激酶和α-1-酸性糖蛋白等组织损伤标志物的血浆水平。（PhSe）（2）预处理可有效降低这些蛋白的水平。此外，（PhSe）（2）可减轻 I / R 引起的脑组织学改变。这项研究首次表明，（PhSe）（2）在体内对大鼠 I / R 损伤引起的氧化应激和促炎细胞因子具有保护作用。
