Renoprotective Effects of Metformin and Its Relationship with Oxidative Stress in Type 2 Diabetic Mice

Abstract

Background: Oxidative stress has previously been shown to play critical roles in the development of diabetes and its complications. The purpose of this research was to observe the reno-protective effect of metformin and its effect on oxidative stress in type 2 diabetic mice renal tissue.Methods: Type 2 diabetes mellitus mice model was established by High-fat feed combined with small-dose STZ and randomly divided into diabetes model group, Metformin [MET, 250mg/(kg.d)] group, Glibenclamide (GLIB) [GLIB, 2.5mg/(kg.d)] group, and normal control group (NC). After 8 weeks of intervention, blood and urine samples were collected for detection of FBG, HbA1c, urine albumin (Alb), retinol-binding protein (RBP), podocalyxin (PCX), 8-OHdG, 8-iso-PG, and creatinine (Cr). Renal tissue specimens were preserved for observing renal glomerular basement membrane thickness (GBMT) and foot process fusion rate (FPFR) under electron microscopy.Results: Compared with the NC group, FBG, HbA1c, urinary Alb/Cr (UACR), RBP/Cr (URCR), PCX/Cr (UPCR), 8-OHdG /Cr (UOHCR), and 8-iso-PG /Cr (UISOCR) significantly increased in the T2DM group (P <0.05). Compared with the T2DM group, FBG, HbA1c, UACR, URCR, UPCR, UOHCR, and UISOCR were significantly reduced in the GLIB group and MET group (P <0.05). Compared to the GLIB group, UACR, URCR, UPCR, UOHCR, and UISOCR decreased in the MET group (P <0.05), but FBG and HbA1c were not differenced statistically between the two groups. GBMT and FPFR increased in the T2DM group (P <0.05), which were reduced in the MET group and lighter than those in the GLIB group (P <0.05).Conclusion: Metformin intervention can play a reno-protective effect in type 2 diabetic mice, which may be related to its effect in inhibiting enhanced oxidative stress in vivo.