Sachdeva Anand Kamal, Kuhad Anurag, Chopra Kanwaljit
Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh-160 014 India.
Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh-160 014 India.
Pharmacol Biochem Behav. 2014 Dec;127:101-10. doi: 10.1016/j.pbb.2014.11.002. Epub 2014 Nov 6.
Mitochondrial dysfunction has been well documented in age related disorders like Alzheimer's disease. Alterations in mitochondrial membrane potential lead to neuronal death by excessive generation of free radicals, inflammatory cytokines, and excitotoxins. Intracerebroventricular (ICV) streptozotocin (STZ) induced-cognitive impairment has been widely used as an experimental model of Alzheimer's disease. Naringin is a potent antioxidant, which can cross the blood brain barrier protecting brain tissue and modulating brain chemistry.
The present study was designed to evaluate the effect of naringin, in ICV STZ-induced mitochondrial dysfunction and memory loss in rats.
Streptozotocin (3mg/kg, ICV) was injected bilaterally in two divided doses on first and third day followed by treatment with different doses of naringin (50, 100 and 200mg/kg; p.o.) for twenty one days. Behavioral alterations were monitored using Morris water maze paradigm and elevated plus maze test. Animals were sacrificed to evaluate various biochemical and mitochondrial parameters in brain. Rivastigmine was used as a standard drug.
ICV-STZ administration produced significant cognitive deficits as assessed by both Morris water maze and elevated plus maze task which is accompanied by significantly enhanced oxidative-nitrosative stress, altered acetylcholinesterase and mitochondrial enzyme activities in cerebral cortex and hippocampus of rats brain along with significantly increased brain TNF-α and IL-1β levels. Chronic treatment with naringin dose dependently restored cognitive deficits in ICV-STZ rat along with mitigation of mitochondrial dysfunction mediated oxido-nitrosative stress and cytokine release.
Our findings demonstrate that naringin ameliorates mitochondrial dysfunction mediated oxido-nitrosative stress and inflammatory surge in ICV-STZ rats.
线粒体功能障碍在诸如阿尔茨海默病等与年龄相关的疾病中已有充分记录。线粒体膜电位的改变会通过自由基、炎性细胞因子和兴奋性毒素的过度产生导致神经元死亡。脑室内（ICV）注射链脲佐菌素（STZ）诱导的认知障碍已被广泛用作阿尔茨海默病的实验模型。柚皮苷是一种有效的抗氧化剂，它可以穿过血脑屏障，保护脑组织并调节脑内化学物质。
本研究旨在评估柚皮苷对ICV注射STZ诱导的大鼠线粒体功能障碍和记忆丧失的影响。
在第一天和第三天分两次双侧注射链脲佐菌素（3mg/kg，ICV），随后用不同剂量的柚皮苷（50、100和200mg/kg；口服）治疗21天。使用莫里斯水迷宫范式和高架十字迷宫试验监测行为改变。处死动物以评估脑内的各种生化和线粒体参数。多奈哌齐用作标准药物。
通过莫里斯水迷宫和高架十字迷宫任务评估，ICV注射STZ导致显著的认知缺陷，同时大鼠脑皮质和海马中的氧化亚硝化应激显著增强、乙酰胆碱酯酶和线粒体酶活性改变，以及脑肿瘤坏死因子-α和白细胞介素-1β水平显著升高。柚皮苷的长期治疗剂量依赖性地恢复了ICV注射STZ大鼠的认知缺陷，并减轻了线粒体功能障碍介导的氧化亚硝化应激和细胞因子释放。
我们的研究结果表明，柚皮苷可改善ICV注射STZ大鼠中线粒体功能障碍介导的氧化亚硝化应激和炎症激增。
