title: Metformin protects the brain against the oxidative imbalance promoted by 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 (H(2)O(2)) 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 H(2)O(2) 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.
authors.affiliation: Center for Neuroscience and Cell Biology, Institute of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Sónia
authors.initials: S
authors.lastname: Correia
authors.forename: Cristina
authors.initials: C
authors.lastname: Carvalho
authors.forename: Maria S
authors.initials: MS
authors.lastname: Santos
authors.forename: Teresa
authors.initials: T
authors.lastname: Proença
authors.forename: Elsa
authors.initials: E
authors.lastname: Nunes
authors.forename: Ana I
authors.initials: AI
authors.lastname: Duarte
authors.forename: Pedro
authors.initials: P
authors.lastname: Monteiro
authors.forename: Raquel
authors.initials: R
authors.lastname: Seiça
authors.forename: Catarina R
authors.initials: CR
authors.lastname: Oliveira
authors.forename: Paula I
authors.initials: PI
authors.lastname: Moreira
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism; D051381:Rats
chemical_list: D001786:Blood Glucose; D011506:Proteins; D008687:Metformin; D006861:Hydrogen Peroxide; D005978:Glutathione