Proteomics Study of Metformin on Lead Ion-Induced Rat Nephropathy

Heavy metal is one of the major causes of kidney damage. The lower blood lead concentration, the fewer kidney damage in clinical observation. Our preliminary study showed that lead ion caused a 1.5 times increase in methylglyoxal concentration in a kidney cell line. Metformin is reported as an effective methylglyoxal scavenger in rat kidney. In this study, we will give 250 ppm of lead ion to rat orally to induce kidney damage in order to evaluate the effects 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 of lead induced kidney damage will be studied. In the second year, the differential proteomics of lead ion and metformin treated kidney will be investigated, and the proteins will be confirmed by western blot. In the third year, the imaging mass spectrometry will be performed to find out the tissue localization of proteins related to kidney damage and metformin treatment. These results will be beneficial to establish the early detection of lead-caused kidney damage and the possible mechanism of metformin on kidney damage