Abstract
We aimed to investigate whether metformin protects the brain against the oxidative imbalance promoted by type 2 diabetes. This study analyzed the effect of metformin on oxidative stress markers (thiobarbituric acid reactive substances (TBARS), malondialdehyde (MDA) and carbonyl groups), hydrogen peroxide (H2O2) levels, non-enzymatic antioxidant defenses [reduced (GSH) and oxidized (GSSG) glutathione and vitamin E] and enzymatic antioxidant defenses [glutathione peroxidase (GPx), glutathione reductase (GRed) and manganese superoxide dismutase (MnSOD)] in brain homogenates of diabetic GK rats, a model of type 2 diabetes. For this purpose we compared brain homogenates obtained from untreated GK rats versus GK rats treated with metformin during a period of 4 weeks. Brain homogenates obtained from Wistar rats were used as control. The MDA levels, GPx and GRed activities are significantly higher in untreated GK rats, while TBARS levels, carbonyl groups, glutathione content and vitamin E levels remain statistically unchanged when compared with control rats. In contrast, MnSOD activity and the levels of H2O2 are significantly decreased in untreated GK rats when compared with control animals. However, metformin treatment normalized the majority of the parameters altered by diabetes. We observed that metformin, besides its antihyperglycemic action, induces a significant decrease in TBARS and MDA levels, GPx and GRed activities and a significant increase in GSH levels and MnSOD activity. These results indicate that metformin protects against diabetes-associated oxidative stress suggesting that metformin could be an effective neuroprotective agent.
Keywords: Brain, metformin, oxidative stress, type 2 diabetes
Medicinal Chemistry
Title: Metformin Protects the Brain Against the Oxidative Imbalance Promoted by Type 2 Diabetes
Volume: 4 Issue: 4
Author(s): Sonia Correia, Cristina Carvalho, Maria S. Santos, Teresa Proenca, Elsa Nunes, Ana I. Duarte, Pedro Monteiro, Raquel Seica, Catarina R. Oliveira and Paula I. Moreira
Affiliation:
Keywords: Brain, metformin, oxidative stress, type 2 diabetes
Abstract: We aimed to investigate whether metformin protects the brain against the oxidative imbalance promoted by type 2 diabetes. This study analyzed the effect of metformin on oxidative stress markers (thiobarbituric acid reactive substances (TBARS), malondialdehyde (MDA) and carbonyl groups), hydrogen peroxide (H2O2) levels, non-enzymatic antioxidant defenses [reduced (GSH) and oxidized (GSSG) glutathione and vitamin E] and enzymatic antioxidant defenses [glutathione peroxidase (GPx), glutathione reductase (GRed) and manganese superoxide dismutase (MnSOD)] in brain homogenates of diabetic GK rats, a model of type 2 diabetes. For this purpose we compared brain homogenates obtained from untreated GK rats versus GK rats treated with metformin during a period of 4 weeks. Brain homogenates obtained from Wistar rats were used as control. The MDA levels, GPx and GRed activities are significantly higher in untreated GK rats, while TBARS levels, carbonyl groups, glutathione content and vitamin E levels remain statistically unchanged when compared with control rats. In contrast, MnSOD activity and the levels of H2O2 are significantly decreased in untreated GK rats when compared with control animals. However, metformin treatment normalized the majority of the parameters altered by diabetes. We observed that metformin, besides its antihyperglycemic action, induces a significant decrease in TBARS and MDA levels, GPx and GRed activities and a significant increase in GSH levels and MnSOD activity. These results indicate that metformin protects against diabetes-associated oxidative stress suggesting that metformin could be an effective neuroprotective agent.
Export Options
About this article
Cite this article as:
Correia Sonia, Carvalho Cristina, Santos S. Maria, Proenca Teresa, Nunes Elsa, Duarte I. Ana, Monteiro Pedro, Seica Raquel, Oliveira R. Catarina and Moreira I. Paula, Metformin Protects the Brain Against the Oxidative Imbalance Promoted by Type 2 Diabetes, Medicinal Chemistry 2008; 4 (4) . https://dx.doi.org/10.2174/157340608784872299
DOI https://dx.doi.org/10.2174/157340608784872299 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Potentialities of Induced Pluripotent Stem (iPS) Cells for Treatment of Diseases
Current Molecular Medicine Cross-Talk Between NO Synthase Isoforms in Neuro-Inflammation: Possible Implications in HIV-Associated Neurocognitive Disorders
Current Medicinal Chemistry NSAIDs Induced Regulation of Alternatively Spliced Transcript Isoforms: Possible Role in Cancer and Alzheimer Disease
Current Cancer Drug Targets Impact of Metformin on Male Reproduction
Current Pharmaceutical Design Overview of PCTK3/CDK18: A Cyclin-Dependent Kinase Involved in Specific Functions in Post-Mitotic Cells
Current Medicinal Chemistry Antioxidants and its Properties as Affected by Extrusion Process: A Review
Recent Patents on Food, Nutrition & Agriculture High-dose Vitamin D Supplementation on Type 1 Diabetes Mellitus Patients: Is there an Improvement in Glycemic Control?
Current Diabetes Reviews Vascular Endothelial Growth Factor in Central Nervous System Injuries – A Vascular Growth Factor Getting Nervous?
Current Neurovascular Research Minocycline Mediated Mitochondrial Cytoprotection: Premises for Therapy of Cerebrovascular and Neurodegenerative Diseases
Current Drug Targets Emerging Therapies for Diabetic Neuropathy: A Clinical Overview
Current Diabetes Reviews Ring Finger Ubiquitin Protein Ligases and Their Implication to the Pathogenesis of Human Diseases
Current Pharmaceutical Design Patent Selections
Recent Patents on Food, Nutrition & Agriculture New Therapeutic Strategies for Cancer and Neurodegeneration Emerging from Yeast Cell-based Systems
Current Pharmaceutical Design Etanercept Improves Cognitive Performance and Increases eNOS and BDNF Expression During Experimental Vascular Dementia in Streptozotocin- induced Diabetes
Current Neurovascular Research A Comprehensive Review on the Biological and Pharmacological Activities of Rhodanine Based Compounds for Research and Development of Drugs
Mini-Reviews in Medicinal Chemistry Recent Patents Relating to siRNAs and Therapeutic Strategies for Genetic Diseases
Recent Patents on DNA & Gene Sequences Salen Mn Complexes Mitigate Radiation Injury in Normal Tissues
Anti-Cancer Agents in Medicinal Chemistry Novel Targets in Multiple Sclerosis: To Oxidative Stress and Beyond
Current Topics in Medicinal Chemistry Meet Our Editorial Board Member
Current Drug Targets Targeting Adenosine Signaling to Treatment of Diabetic Nephropathy
Current Drug Targets