Metformin protects the brain against the oxidative imbalance promoted by type 2 diabetes

被引:96
作者
Correia, Sonia [2 ]
Carvalho, Cristina [2 ]
Santos, Maria S. [2 ,3 ]
Proenca, Teresa [3 ,4 ]
Nunes, Elsa [3 ,6 ]
Duarte, Ana I. [2 ,3 ]
Monteiro, Pedro [5 ]
Seica, Raquel [3 ,6 ]
Oliveira, Catarina R. [1 ,3 ]
Moreira, Paula I. [3 ,6 ]
机构
[1] Univ Coimbra, Ctr Neurosci & Cell Biol, Fac Med, Inst Biochem,Inst Phys, P-3000354 Coimbra, Portugal
[2] Coimbra Univ Hosp, Fac Sci & Technol, Dept Zool, Coimbra, Portugal
[3] Coimbra Univ Hosp, Ctr Neurosci & Cell Biol, Coimbra, Portugal
[4] Coimbra Univ Hosp, Dept Neurol, Coimbra, Portugal
[5] Coimbra Hosp Univ, Dept Cardiol, Coimbra, Portugal
[6] Coimbra Hosp Univ, Fac Med, Inst Physiol, Coimbra, Portugal
关键词
brain; metformin; oxidative stress; type; 2; diabetes;
D O I
10.2174/157340608784872299
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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.
引用
收藏
页码:358 / 364
页数:7
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