Al-Majed Abdulhakeem A, Al-Omar Fadhel A, Nagi Mahmoud N
Department of Pharmacology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Eur J Pharmacol. 2006 Aug 14;543(1-3):40-7. doi: 10.1016/j.ejphar.2006.05.046. Epub 2006 Jun 3.
Increasing evidence demonstrates that oxidative stress plays an important role in brain injury in experimental models of brain ischemia. Thymoquinone, the main constituents of the volatile oil from Negella sativa seeds, is reported to possess strong antioxidant properties. Hence, the present study was undertaken to evaluate the neuroprotective effect of thymoquinone against transient forebrain ischemia-induced neuronal damage in the rat hippocampus. Rats were divided randomly into five groups: control, sham, ischemia, thymoquinone and ischemia+thymoquinone. Transient forebrain ischemia was induced with bilateral occlusion of both common carotid arteries for 10 min followed by 7 days of reperfusion. Thymoquinone was administered (5 mg/kg/day p.o.) 5 days before ischemia and continued during the reperfusion time. Animals were sacrificed, and brain tissues were isolated for histopathological examination. Hippocampal tissues were also used for determination of malondialdehyde levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant and the activities of the antioxidant enzymes catalase and superoxide dismutase (SOD). Thymoquinone and its metabolite thymohydroquinone were tested as inhibitors of the in vitro non-enzymatic lipid peroxidation induced by iron-ascorbate in the hippocampal homogenate. Forebrain ischemia-reperfusion neural injury in rats was demonstrated by histopathological observation, which revealed significant neural cell death in the hippocampus CA1 area 7 days post-ischemia (77% cell loss). Additionally, forebrain ischemia-reperfusion oxidative injury in rats was demonstrated by a significant increase in malondialdehyde and a significant decrease in GSH contents, catalase and SOD activities in the hippocampal tissue compared to the control or sham-operated groups. Pretreatment of thymoquinone attenuated forebrain ischemia-induced neuronal damage manifested by significantly decreasing the number of dead hippocampal neuronal cells (24% in thymoquinone-treated versus 77% for ischemia, P<0.001), which confirm the protective role of thymoquinone in ischemia-reperfusion injury. Also, pretreatment of ischemic rats with thymoquinone decreased the elevated levels of malondialdehyde and increased GSH contents, catalase and SOD activities to normal levels. Thymoquinone and thymohydroquinone inhibited the in vitro non-enzymatic lipid peroxidation in hippocampal homogenate induced by iron-ascorbate. The IC50 for thymoquinone and thymohydroquinone were found to be 12 and 3 microM respectively. This suggests that the protection of thymoquinone and its metabolite involve increased resistance to oxidative stress. In conclusion, thymoquinone is effective in protecting rats against transient forebrain ischemia-induced damage in the rat hippocampus. This spectacular protection makes thymoquinone a promising agent in pathologies implicating neurodegenaration such as cerebral ischemia.
越来越多的证据表明，氧化应激在脑缺血实验模型的脑损伤中起重要作用。黑种草籽挥发油的主要成分百里醌据报道具有很强的抗氧化特性。因此，本研究旨在评估百里醌对大鼠海马体中短暂性前脑缺血诱导的神经元损伤的神经保护作用。将大鼠随机分为五组：对照组、假手术组、缺血组、百里醌组和缺血+百里醌组。通过双侧颈总动脉闭塞10分钟，然后再灌注7天来诱导短暂性前脑缺血。在缺血前5天给予百里醌（5毫克/千克/天，口服），并在再灌注期间持续给药。处死动物，分离脑组织进行组织病理学检查。海马组织也用于测定丙二醛水平（脂质过氧化的终产物）、谷胱甘肽（GSH）水平（一种关键的抗氧化剂）以及抗氧化酶过氧化氢酶和超氧化物歧化酶（SOD）的活性。测试百里醌及其代谢产物氢醌作为海马匀浆中铁-抗坏血酸诱导的体外非酶脂质过氧化的抑制剂。通过组织病理学观察证实了大鼠前脑缺血-再灌注神经损伤，其显示缺血后7天海马CA1区有明显的神经细胞死亡（细胞损失7
