Mohamed A, Shoker A, Bendjelloul F, Mare A, Alzrigh M, Benghuzzi H, Desin T
College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
Biomed Sci Instrum. 2003;39:440-5.
Experimental Allergic Encephalomyelitis (EAE) is an autoimmune demyelinating disease of the central nervous system that is widely accepted as an animal model for the human multiple sclerosis. Oxidative stress appears to play a role in the onset and progression of EAE. We reasoned that decreasing oxidative stress might ameliorate symptoms and signs of EAE. Thymoquinone is reported to inhibit oxidative stress. One way of decreasing oxidative stress is to induce glutathione (GSH). We tested the impact of Thymoquinone (1 mg/kg, injected at tail vein) in our EAE model. We induced (EAE) in female Lewis rats using myelin basic protein emulsified with complete Freund's adjuvant. 24 animals were placed into three groups: A) Rats with EAE B) EAE rats with concomitant five day injection of Thymoquinone days 1-5, C) EAE rats with five doses of Thymoquinone injected at day 12-17. Twenty-eight days later, animals were sacrificed; spinal cord tissues collected for glutathione (GSH).
63% of animals in group "A" developed hind limb weakness and/or paralysis while 37% developed mild tail weakness, perivascular inflammation and low spinal cord GSH level. 25% of animals in group "B" exhibited mild tail and hind limb weakness and 75% animals had no symptoms, no perivascular inflammation and high spinal cord GSH level. 63% of animals of group "C" showed improving symptoms following Thymoquinone injections, no perivascular inflammation and higher GSH level while 37% of animals showed no symptoms prior and post Thymoquinone injections. Clinical symptoms correlated well with perivascular inflammation and GSH level. Animals received Thymoquinone at day 12-17 had higher GSH level, no perivascular inflammation and no symptoms compared with other groups.
Thymoquinone inhibited oxidative stress which leads into improvement in our EAE animals. Thymoquinone may have a role in treatment of Multiple Sclerosis.
实验性自身免疫性脑脊髓炎(EAE)是一种中枢神经系统的自身免疫性脱髓鞘疾病,被广泛认为是人类多发性硬化症的动物模型。氧化应激似乎在EAE的发病和进展中起作用。我们推测降低氧化应激可能会改善EAE的症状和体征。据报道,百里醌可抑制氧化应激。降低氧化应激的一种方法是诱导谷胱甘肽(GSH)。我们在EAE模型中测试了百里醌(1mg/kg,经尾静脉注射)的影响。我们使用与完全弗氏佐剂乳化的髓鞘碱性蛋白在雌性Lewis大鼠中诱导EAE。将24只动物分为三组:A)患有EAE的大鼠;B)在第1至5天同时注射五天百里醌的EAE大鼠;C)在第12至17天注射五剂百里醌的EAE大鼠。28天后,处死动物;收集脊髓组织用于检测谷胱甘肽(GSH)。
“A”组63%的动物出现后肢无力和/或麻痹,37%的动物出现轻度尾巴无力、血管周围炎症和脊髓GSH水平降低。“B”组25%的动物表现出轻度尾巴和后肢无力,75%的动物没有症状、没有血管周围炎症且脊髓GSH水平高。“C”组63%的动物在注射百里醌后症状改善,没有血管周围炎症且GSH水平较高,而37%的动物在注射百里醌前后均无症状。临床症状与血管周围炎症和GSH水平密切相关。与其他组相比,在第12至17天接受百里醌的动物GSH水平更高,没有血管周围炎症且没有症状。
百里醌抑制氧化应激,从而改善我们的EAE动物模型。百里醌可能在多发性硬化症的治疗中发挥作用。