Nampoothiri Madhavan, Ramalingayya Grandhi Venkata, Kutty Nampurath Gopalan, Krishnadas Nandakumar, Rao Chamallamudi Mallikarjuna
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India-576104.
Discovery Biology, Suven Life Sciences Ltd., Pashamylaram, Medak District, Telangana-503307, India; Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal-576104, Karnataka, India.
J Environ Pathol Toxicol Oncol. 2017;36(2):159-169. doi: 10.1615/JEnvironPatholToxicolOncol.2017020185.
Therapeutic intervention using drugs against Alzheimer disease is curative clinically. At present, there are no reports on the curative role of insulin in chronic models of dementia. We evaluated the curative role of insulin and its combination with glucose in dementia. We also investigated the impact of treatments on blood glucose to correlate with cognitive deficit. Further, we analyzed the interaction of treatments with the cholinergic system and oxidative stress in memory centers (i.e., hippocampus and frontal cortex). The antidementia activity of insulin was assessed against aluminum chloride (AlCl3)-induced dementia in rats. Behavioral parameters (Morris water maze test) along with biochemical parameters (Hippocampus and frontal cortex) such as acetylcholinesterase (AChE), catalase, and glutathione (GSH) levels were assessed to correlate cognitive function with cholinergic transmission and oxidative stress. Rats administered insulin and glucose showed improved cognitive function in the Morris water maze test. The combination corrected the diminished level of antioxidant enzymes such as catalase and GSH in the hippocampus and frontal cortex.Combined administration of insulin and glucose to aluminum-treated rats did not inhibit the aluminum action on the acetylcholinesterase enzyme. No significant changes were observed in blood glucose levels between the treatment groups.
使用药物治疗阿尔茨海默病在临床上具有治愈作用。目前,尚无关于胰岛素在慢性痴呆模型中治愈作用的报道。我们评估了胰岛素及其与葡萄糖联合使用在痴呆治疗中的作用。我们还研究了治疗对血糖的影响,以将其与认知缺陷相关联。此外,我们分析了治疗与记忆中枢(即海马体和额叶皮质)中的胆碱能系统和氧化应激之间的相互作用。评估了胰岛素对大鼠氯化铝(AlCl3)诱导的痴呆的抗痴呆活性。评估行为参数(莫里斯水迷宫试验)以及生化参数(海马体和额叶皮质),如乙酰胆碱酯酶(AChE)、过氧化氢酶和谷胱甘肽(GSH)水平,以将认知功能与胆碱能传递和氧化应激相关联。给予胰岛素和葡萄糖的大鼠在莫里斯水迷宫试验中显示出改善的认知功能。该组合纠正了海马体和额叶皮质中过氧化氢酶和GSH等抗氧化酶水平的降低。对经铝处理的大鼠联合给予胰岛素和葡萄糖并未抑制铝对乙酰胆碱酯酶的作用。各治疗组之间的血糖水平未观察到显著变化。