MO628IMPACT OF INDUCTION OF AUTOPHAGY BY RAPAMYCIN AND METFORMIN ON NATURAL HISTORY OF DIABETIC NEPHROPATHY IN RATS

Abstract

Abstract Background and Aims Impaired autophagy in the kidney resulted in podocyte loss and massive proteinuria in diabetic nephropathy. Improvement of autophagy by activation of mTORC1 and reduction of AMPK and Sirt1 may be a novel therapeutic option for the suppression of diabetic nephropathy. Method This experimental work was carried out on 48 adult male Sprague dawely rats. The total duration of the study was 10 weeks. All investigation and intervention were carried out at 3 time points, 3 weeks, 6 weeks, 10 weeks. The rats were randomly divided into healthy control group (n = 12) and 3 induced diabetic groups (n = 12 each), the three groups were the non-treated, treated with rapamycin and treated with rapamycin and metformin. To study autophagy, we use electron microscopy and immunohistochemical staining of kidney tissue with LC3 antibody Results Diabetic rats treated with rapamycin alone or rapamycin and metformin showed lower level of proteinuria and almost normal serum creatinine through all intervals of the study. Also, their Kidney tissue showed increased autophagosomes and high expression of LC3 compared to diabetic rats. There are no significant differences between both treated groups in terms of induction of autophagy during the experiment period. Conclusion we concluded that using a small dose of rapamycin for short duration in early diabetic rats is beneficial in halting the course of diabetic nephropathy, adding metformin to rapamycin aiming to potentiate its effect on autophagy seems to be less beneficial.