Jabeen Komal, Rehman Kanwal, Akash Muhammad Sajid Hamid, Nadeem Ahmed, Mir Tahir Maqbool
Institute of Physiology and Pharmacology, University of Agriculture, Faisalabad 38000, Pakistan.
Department of Pharmacy, Niazi Medical and Dental College, Sargodha 40100, Pakistan.
Biomedicines. 2023 Sep 4;11(9):2453. doi: 10.3390/biomedicines11092453.
Cardiovascular diseases (CVDs) and neurodegenerative disorders, such as diabetes mellitus and Alzheimer's disease, share a common pathophysiological link involving insulin resistance (IR), inflammation, and hypertension. Aluminium chloride (AlCl), a known neurotoxicant, has been associated with neurodegeneration, cognitive impairment, and various organ dysfunctions due to the production of reactive oxygen species (ROS) and oxidative stress. In this study, we aimed to investigate the potential protective effects of metformin and vitamin E against AlCl-induced neuroinflammation and cardiometabolic disturbances in rat models. Rats were divided into five groups: a normal control group, an AlCl-treated diseased group without any treatment, and three groups exposed to AlCl and subsequently administered with metformin (100 mg/kg/day) alone, vitamin E (150 mg/kg/day) orally alone, or a combination of metformin (100 mg/kg/day) and vitamin E (150 mg/kg/day) for 45 days. We analyzed serum biomarkers and histopathological changes in brain, heart, and pancreatic tissues using H&E and Masson's trichrome staining and immunohistochemistry (IHC). Electrocardiogram (ECG) patterns were observed for all groups. The AlCl-treated group showed elevated levels of inflammatory biomarkers, MDA, and disturbances in glycemic and lipid profiles, along with reduced insulin levels. However, treatment with the combination of metformin and vitamin E resulted in significantly reduced glucose, cholesterol, LDL, and TG levels, accompanied by increased insulin and HDL levels compared to the individual treatment groups. Histopathological analyses revealed that combination therapy preserved neuronal structures, muscle cell nuclei, and normal morphology in the brain, heart, and pancreatic tissues. IHC demonstrated reduced amyloid plaques and neurofibrillary tangles in the combination-treated group compared to the AlCl-treated group. Moreover, the combination group showed a normal ECG pattern, contrasting the altered pattern observed in the AlCl-treated group. Overall, our findings suggest that metformin and vitamin E, in combination, possess neuroprotective and cardiometabolic effects, alleviating AlCl-induced neuroinflammation and metabolic disturbances.
心血管疾病（CVDs）和神经退行性疾病，如糖尿病和阿尔茨海默病，有着涉及胰岛素抵抗（IR）、炎症和高血压的共同病理生理联系。氯化铝（AlCl）是一种已知的神经毒素，由于活性氧（ROS）的产生和氧化应激，它与神经退行性变、认知障碍和各种器官功能障碍有关。在本研究中，我们旨在研究二甲双胍和维生素E对氯化铝诱导的大鼠模型神经炎症和心脏代谢紊乱的潜在保护作用。将大鼠分为五组：正常对照组、未接受任何治疗的氯化铝处理疾病组，以及三组暴露于氯化铝后分别单独给予二甲双胍（100毫克/千克/天）、单独口服维生素E（150毫克/千克/天）或二甲双胍（100毫克/千克/天）与维生素E（150毫克/千克/天）联合用药45天的组。我们使用苏木精和伊红（H&E）染色、马松三色染色和免疫组织化学（IHC）分析了大脑、心脏和胰腺组织中的血清生物标志物以及组织病理学变化。观察了所有组的心电图（ECG）模式。氯化铝处理组显示炎症生物标志物、丙二醛（MDA）水平升高，血糖和血脂谱紊乱，同时胰岛素水平降低。然而，与单独治疗组相比，二甲双胍和维生素E联合治疗导致葡萄糖、胆固醇、低密度脂蛋白（LDL）和甘油三酯（TG）水平显著降低，同时胰岛素和高密度脂蛋白（HDL）水平升高。组织病理学分析表明，联合治疗保留了大脑、心脏和胰腺组织中的神经元结构、肌细胞核和正常形态。免疫组织化学显示，与氯化铝处理组相比，联合治疗组的淀粉样斑块和神经原纤维缠结减少。此外，联合治疗组显示心电图模式正常，与氯化铝处理组观察到的异常模式形成对比。总体而言，我们的研究结果表明，二甲双胍和维生素E联合使用具有神经保护和心脏代谢作用，可减轻氯化铝诱导的神经炎症和代谢紊乱。
