RESUMO
Metformin is used to reduce hyperglycemia that induces energetic stress and leads to reduction in gluconeogenesis. Also, metformin inhibits complex I in oxidative phosphorylation, thereby decreasing cellular ATP levels. Activation of AMPK by the reduced ATP levels can induce inhibition of reactive oxygen species (ROS) production and activate p53-mediated DNA repair. DNA polymerase-ß and XRCC1 function to repair DNA damages in the BER (base excision repair) system. In type 2 diabetes patients, metformin can enhance AMPK activation therefore suppress oxidative stress. The changes on oxidative stress may alter p53's function and effect many cellular pathways such as; DNA repair. In our project we aim to understand the effects of metformin on p53 and DNA-BER system based on the oxidative status in type 2 diabetes patients. Oxidative and antioxidative capacity, catalase, SOD, GPx activities and, DNA pol beta, XRCC1 and p53 levels were measured in metformin using or non-using type 2 diabetes patients and controls. Metformin enhanced SOD and GPx activities in type 2 diabetes patients but the reflection of this increase to the total antioxidant capacity was not significant. Although the increase in DNA pol beta was not significant, XRCC1 and p53 levels were significantly upregulated with metformin treatment in type 2 diabetes patients. Our study reinforces the potential benefit of metformin in antioxidative capacity to protect cells from diabetic oxidative stress and in regulation of DNA BER system.
