Proteomic Study of Metformin on Kidney Damage in Rats

Gentamicin is a widely used aminoglycoside antibiotic, but its kidney toxicity has limited its clinical application. In our previous study, we showed that gentamicin caused the increase in renal methylglyoxal and D-lactate concentration. Since metformin reduces systemic methylglyoxal levels, in this study, we will intraperitoneally inject 150 mg/Kg/day of gentamicin to rat to induce kidney damage in order to evaluate the effect of metformin. Proteomic study of the kidney tissue will be performed by using fluorescent high-performance liquid phase chromatography tandem mass spectrometry (FD-LC-MS/MS) method to understand the role and the relationship between metformin and the injury. Then the proteomic study of blood and urine samples will be investigated for clinical application. In the first year, the effect of metformin on methylglyoxal, blood urea nitrogen (BUN), creatinine, urinary enzymes NAG, urine protein content and renal biopsy will be studied. In the second year, the differential proteomics of gentamicin and metformin treated kidney will be investigated, and the proteins will be confirmed by western blot. In the third year, the proteomic analysis of blood and urine samples will be performed to find out the proteins related to kidney damage and metformin effect. These results will be beneficial to establish the early detection of gentamicin-caused renal injury and the possible mechanism of metformin on kidney damage.