Doxycycline: An antibiotic with brain protective function in vanadium-intoxicated rats

Negia Emtawel Mohamed, E. Gassar, S. Abdulla, M. Elfakhri, Ayyub A Patel, S. Haider
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引用次数: 2

Abstract

Background: Exposure to vanadium exhibits deleterious neurotoxicity. Doxycycline is a potential antioxidant that prevents the progression of disease through inhibition of lipid peroxidation. Objectives: This research investigates the neuroprotective effects of doxycycline, in different rat brain areas in an animal model intoxicated with vanadium. Materials and Methods: Male Sprague-Dawley rats were equally divided into the following four groups: control group, doxycycline-treated group, vanadium-treated group, and concomitant doses of doxycycline plus vanadium-treated group, all given orally for 10 consecutive days. The animals were watched daily for any signs of neurological defects. They were sacrificed by decapitation 24 h after the last dose. Brain was removed rapidly and dissected into cerebral cortex, cerebellum, and brain stem. Biochemical studies including the concentrations of phospholipids, cholesterol, cerebrosides, glutathione (GSH), acetylcholinesterase (AChE) activity, gangliosides, ascorbic acid, calcium, and lipid peroxidation levels were determined. Results: The results revealed that vanadium produced significant reduction in body and absolute brain weight, with neurological function deficits. Vanadium significantly decreased the concentrations of phospholipids, cholesterol, cerebrosides, and GSH and inhibited AChE activity together with significant increase in gangliosides, ascorbic acid, calcium, and lipid peroxidation levels compared to saline controls. Animals which were given the combined treatment of vanadium and doxycycline regained weight and became normal. Moreover, doxycycline reversed the effect of vanadium on the metabolic variables and inhibited lipid peroxidation nearing to normal levels to that of saline controls. Conclusion: These findings demonstrated the antioxidant or chelating action of doxycycline against vanadium neurotoxicity and its therapeutic potential to avert neurodegenerative changes in different rat brain areas.
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多西环素:一种对钒中毒大鼠具有脑保护作用的抗生素
背景:暴露于钒表现出有害的神经毒性。强力霉素是一种潜在的抗氧化剂,通过抑制脂质过氧化作用来防止疾病的进展。目的:研究多西环素在钒中毒大鼠不同脑区的神经保护作用。材料与方法:雄性sd大鼠随机分为对照组、强力霉素组、钒处理组和强力霉素加钒同时给药组,连续口服10 d。每天观察这些动物是否有任何神经缺陷的迹象。末次给药后24 h处死。迅速取脑,解剖大脑皮层、小脑、脑干。生化研究包括磷脂、胆固醇、脑苷、谷胱甘肽(GSH)、乙酰胆碱酯酶(AChE)活性、神经节苷、抗坏血酸、钙和脂质过氧化水平的测定。结果:结果显示,钒使机体和绝对脑重明显减少,并伴有神经功能缺损。与生理盐水对照组相比,钒显著降低了磷脂、胆固醇、脑苷和谷胱甘肽的浓度,抑制了乙酰胆碱酯酶活性,同时显著增加了神经节苷、抗坏血酸、钙和脂质过氧化水平。给予钒和强力霉素联合治疗的动物体重恢复正常。此外,强力霉素逆转了钒对代谢变量的影响,并抑制脂质过氧化接近正常水平,达到生理盐水对照组的水平。结论:多西环素对钒的神经毒性具有抗氧化或螯合作用,具有防止大鼠不同脑区神经退行性改变的治疗潜力。
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