Kuhad Anurag, Sethi Richa, Chopra Kanwaljit
Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh-160 014, India.
Life Sci. 2008 Jul 18;83(3-4):128-34. doi: 10.1016/j.lfs.2008.05.013. Epub 2008 Jun 8.
Diabetes-induced learning and memory impairment, characterized by impaired cognitive functions and neurochemical and structural abnormalities, involve direct neuronal damage caused by intracellular glucose. The present study was designed to investigate the effect of lycopene, a potent anti-oxidant and anti-inflammatory molecule, on cognitive functions, oxidative stress and inflammation in streptozotocin (STZ)-induced diabetic rats. Cognitive functions were investigated using a spatial version of the Morris water maze test. Acetylcholinesterase activity, a marker of cholinergic dysfunction, was increased by 1.8 fold in the cerebral cortex of diabetic rats. There was about 2 fold and 2.2 fold rise in thiobarbituric acid-reactive substance levels in cerebral cortex and hippocampus of diabetic rats, respectively. Non-protein thiol levels and enzymatic activities of superoxide dismutase and catalase were decreased in both cerebral cortex and hippocampal regions of diabetic rat brain. Total nitric oxide levels in cerebral cortex and hippocampus was increased by 2.4 fold and 2 fold respectively. Serum tumor necrosis factor-alpha, an inflammatory marker, was found to increase by 8 fold in diabetic rats. Chronic treatment with lycopene (1, 2 and 4 mg/kg; p.o.) significantly and dose dependently attenuated cognitive deficit, increased acetylcholinesterase activity, oxidative-nitrosative stress and inflammation in diabetic rats. The results emphasize the involvement of oxidative-nitrosative stress and peripheral inflammation in the development of cognitive impairment in diabetic animals and point towards the therapeutic potential of lycopene in diabetes-induced learning and memory impairment.
糖尿病引起的学习和记忆障碍，其特征为认知功能受损以及神经化学和结构异常，涉及细胞内葡萄糖导致的直接神经元损伤。本研究旨在探讨番茄红素（一种强效抗氧化剂和抗炎分子）对链脲佐菌素（STZ）诱导的糖尿病大鼠认知功能、氧化应激和炎症的影响。使用空间版的莫里斯水迷宫试验研究认知功能。糖尿病大鼠大脑皮层中乙酰胆碱酯酶活性（胆碱能功能障碍的标志物）增加了1.8倍。糖尿病大鼠大脑皮层和海马体中硫代巴比妥酸反应性物质水平分别升高了约2倍和2.2倍。糖尿病大鼠脑的大脑皮层和海马区中非蛋白质硫醇水平以及超氧化物歧化酶和过氧化氢酶的酶活性均降低。大脑皮层和海马体中的总一氧化氮水平分别增加了2.4倍和2倍。发现糖尿病大鼠血清中炎症标志物肿瘤坏死因子-α增加了8倍。用番茄红素（1、2和4毫克/千克；口服）进行慢性治疗可显著且剂量依赖性地减轻糖尿病大鼠的认知缺陷，增加乙酰胆碱酯酶活性、氧化亚硝化应激和炎症。结果强调了氧化亚硝化应激和外周炎症在糖尿病动物认知障碍发展中的作用，并指出了番茄红素在糖尿病引起的学习和记忆障碍中的治疗潜力。
