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
-
Commentary: Stephen William Hawking (8 January 1942 – 14 March 2018)
CNS & Neurological Disorders - Drug Targets Mesenchymal Stem Cell-Based Therapy for the Treatment of Type 1 Diabetes Mellitus
Current Stem Cell Research & Therapy Advanced Glycation End Products (AGEs) and their Receptor (RAGE) System in Diabetic Retinopathy
Current Drug Discovery Technologies Editorial [Hot Topic: New Insight in Obesity and Insulin Resistance (Guest Editor: Geltrude Mingrone)]
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Resolvins: Endogenously-Generated Potent Painkilling Substances and their Therapeutic Perspectives
Current Neuropharmacology The Role of Iron Toxicity in Oxidative Stress-induced Cellular Degeneration in Down Syndrome: Protective Effects of Phenolic Antioxidants
Current Nutrition & Food Science The Molecular Basis of Conantokin Antagonism of NMDA Receptor Function
Current Drug Targets Non-Steroidal Anti-Inflammatory Drugs as Anti-Amyloidogenic Compounds
Current Pharmaceutical Design Control and Role of Plateau Potential Properties in the Spinal Cord
Current Pharmaceutical Design Kainic Acid-Induced Neurotoxicity: Targeting Glial Responses and Glia-Derived Cytokines
Current Neuropharmacology The Role of Microglial Cells on Neuroinflammation: Possible Therapeutic Applications
Recent Patents on Regenerative Medicine The Role of H. pylori Infection in Diabetes
Current Diabetes Reviews Inflammation in the CNS: Understanding Various Aspects of the Pathogenesis of Alzheimer's Disease
Current Alzheimer Research Over-nutrition, Obesity and Insulin Resistance in the Development of β-Cell Dysfunction
Current Diabetes Reviews GABAA Receptor Specific Pyrazolopyrimidines as Potential Imaging Agents: In Vivo Characteristics of a New 18F-labelled Indiplon Derivative
Current Radiopharmaceuticals Editorial [Hot Topic: Tocotrienols: Potential Drug Targets for Cardiovascular, Cancer and Neurological Diseases (Executive Guest Editor: Dipak K. Das)]
Current Pharmaceutical Design Protein Misfolding in Disease and Small Molecule Therapies
Current Topics in Medicinal Chemistry Neuronal and Glial Cell Abnormality as Predictors of Progression of Diabetic Retinopathy
Current Pharmaceutical Design Methylation Profile of miR-9-1 and miR-9-1/-9-3 as Potential Biomarkers of Diabetic Retinopathy
Current Diabetes Reviews Neuronal Death and Survival Under Oxidative Stress in Alzheimer and Parkinson Diseases
CNS & Neurological Disorders - Drug Targets