Neuroprotective and Cardiometabolic Role of Vitamin E: Alleviating Neuroinflammation and Metabolic Disturbance Induced by AlCl<sub>3</sub> in Rat Models
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<sub>3</sub>), a known neurotoxicant, has b...
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2023-09-01
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author | Komal Jabeen Kanwal Rehman Muhammad Sajid Hamid Akash Ahmed Nadeem Tahir Maqbool Mir |
author_facet | Komal Jabeen Kanwal Rehman Muhammad Sajid Hamid Akash Ahmed Nadeem Tahir Maqbool Mir |
author_sort | Komal Jabeen |
collection | DOAJ |
description | 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<sub>3</sub>), 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<sub>3</sub>-induced neuroinflammation and cardiometabolic disturbances in rat models. Rats were divided into five groups: a normal control group, an AlCl<sub>3</sub>-treated diseased group without any treatment, and three groups exposed to AlCl<sub>3</sub> 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<sub>3</sub>-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<sub>3</sub>-treated group. Moreover, the combination group showed a normal ECG pattern, contrasting the altered pattern observed in the AlCl<sub>3</sub>-treated group. Overall, our findings suggest that metformin and vitamin E, in combination, possess neuroprotective and cardiometabolic effects, alleviating AlCl<sub>3</sub>-induced neuroinflammation and metabolic disturbances. |
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spelling | doaj.art-b3e7d2076df24a1ca2681af458880d702023-11-19T09:41:31ZengMDPI AGBiomedicines2227-90592023-09-01119245310.3390/biomedicines11092453Neuroprotective and Cardiometabolic Role of Vitamin E: Alleviating Neuroinflammation and Metabolic Disturbance Induced by AlCl<sub>3</sub> in Rat ModelsKomal Jabeen0Kanwal Rehman1Muhammad Sajid Hamid Akash2Ahmed Nadeem3Tahir Maqbool Mir4Institute of Physiology and Pharmacology, University of Agriculture, Faisalabad 38000, PakistanDepartment of Pharmacy, The Women University, Multan 66000, PakistanDepartment of Pharmaceutical Chemistry, Government College University, Faisalabad 38000, PakistanDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaNational Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS 38677, USACardiovascular 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<sub>3</sub>), 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<sub>3</sub>-induced neuroinflammation and cardiometabolic disturbances in rat models. Rats were divided into five groups: a normal control group, an AlCl<sub>3</sub>-treated diseased group without any treatment, and three groups exposed to AlCl<sub>3</sub> 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<sub>3</sub>-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<sub>3</sub>-treated group. Moreover, the combination group showed a normal ECG pattern, contrasting the altered pattern observed in the AlCl<sub>3</sub>-treated group. Overall, our findings suggest that metformin and vitamin E, in combination, possess neuroprotective and cardiometabolic effects, alleviating AlCl<sub>3</sub>-induced neuroinflammation and metabolic disturbances.https://www.mdpi.com/2227-9059/11/9/2453neuroinflammationcardiometabolic disturbanceimmunohistochemistryMasson’s trichrome staining |
spellingShingle | Komal Jabeen Kanwal Rehman Muhammad Sajid Hamid Akash Ahmed Nadeem Tahir Maqbool Mir Neuroprotective and Cardiometabolic Role of Vitamin E: Alleviating Neuroinflammation and Metabolic Disturbance Induced by AlCl<sub>3</sub> in Rat Models Biomedicines neuroinflammation cardiometabolic disturbance immunohistochemistry Masson’s trichrome staining |
title | Neuroprotective and Cardiometabolic Role of Vitamin E: Alleviating Neuroinflammation and Metabolic Disturbance Induced by AlCl<sub>3</sub> in Rat Models |
title_full | Neuroprotective and Cardiometabolic Role of Vitamin E: Alleviating Neuroinflammation and Metabolic Disturbance Induced by AlCl<sub>3</sub> in Rat Models |
title_fullStr | Neuroprotective and Cardiometabolic Role of Vitamin E: Alleviating Neuroinflammation and Metabolic Disturbance Induced by AlCl<sub>3</sub> in Rat Models |
title_full_unstemmed | Neuroprotective and Cardiometabolic Role of Vitamin E: Alleviating Neuroinflammation and Metabolic Disturbance Induced by AlCl<sub>3</sub> in Rat Models |
title_short | Neuroprotective and Cardiometabolic Role of Vitamin E: Alleviating Neuroinflammation and Metabolic Disturbance Induced by AlCl<sub>3</sub> in Rat Models |
title_sort | neuroprotective and cardiometabolic role of vitamin e alleviating neuroinflammation and metabolic disturbance induced by alcl sub 3 sub in rat models |
topic | neuroinflammation cardiometabolic disturbance immunohistochemistry Masson’s trichrome staining |
url | https://www.mdpi.com/2227-9059/11/9/2453 |
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