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.
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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 |
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