Fp459abnormal Serum Levels of Nitrotyrosine-Associated Proteins and Renal Protective Potential of Polyphenolic Extracts in Wistar Rats With Experimentally Induced Diabetes

Abstract

Introduction and Aims: In hyperglycemic conditions, renal tubular cells generate increased amounts of nitric oxide, superoxide anion, peroxynitrites, nitrotyrosine-bound proteins. The mechanisms by which several natural polyphenolic compounds could provide protection of kidney function and could limit tubular damage in diabetic nephropathy is an exciting chapter of experimental pharmacology. The aim of the study was evaluation of the relationship between serum levels of 3-nitrotyrosine, the final product of protein oxidation, and creatinine level in rats with alloxan diabetes.Methods: In Wistar male rats for inducing alloxan diabetes (130mg/ kg body) which. For the treatment of induced diabetes, natural polyphenolic extracts (Betulae folium BE, Rubi idaei folium RE) were used. The rats with non-insulin dependent diabetes were divided into 6 groups (12 animals /group) as follows: group 1 -untreated diabetes; group 2 -diabetes treated with metformin; group 3 -diabetes treated with BE; group 4 -diabetes treated with metformin and BE; group 5 -diabetes treated with RE; group 6 -diabetes treated with metformin + RE. Group 7, the control group, included non-diabetes rats (12 animals). Serum concentration of 3-nitrotyrosine was determined by immunoezymatic technique, and glycaemia, creatininemia and proteinuria were evaluated using photometric method. Results: Significantly higher values of associated protein nitrotyrosine (mol /mg protein) were determined in diabetic rats were compared with non-diabetes rats: 494.3 ± 38.9-group 1; 501.1 ± 52.7-group 2; 463.3 ± 88.1-group 3; 478.5 ± 55.1-group 4; 482.4 ± 39.4-group 5; 476.3 ± 29.5 -group 6 versus group 7: 99.7 ± 19.4 ( p <0.05). A positive relation between the level of tyrosine-bound proteins and creatininemia was observed in untreated diabetes rats (r = 0.43, p 0.05); diabetes treated with BE (r = 0.51, p <0.05); diabetes treated with metformin and BE (r = 0.25, p <0.05); diabetes treated with RE (r = 0.59, p <0.05); diabetes treated with metformin and RE (r = 0.32, p 0.05). Conclusions: Significant increase in serum levels of nitrotyrosine-associated proteins in rats with diabetic nephropathy could be a determining factor in the initiation and progression of microvascular complications of dyabetes. Polyphenolic extracts administered in Wistar rats with experimentally induced diabetes initiates a series of events were associated with the reduction of serum levels of nitrotyrosine-bound proteins.