The effects of angiotensin-II receptor blockers on podocyte damage and glomerular apoptosis in a rat model of experimental streptozotocin-induced diabetic nephropathy

The aim of the study was to determine in a rat model of streptozotocin-induced diabetic nephropathy the expression of: WT-1 (for podocyte loss in the glomerulus), TGF-beta 1 (for tissue damage), caspase-3 and bax (for glomerular apoptosis) and the possible protective effects of an angiotensin II type 1 receptor blocker. Three groups of male Wistar albino rats were used. The first group consisted of non-diabetic control rats. The second group was the untreated diabetic rats. The third group consisted of diabetic rats treated with Irbesartan, which is an angiotensin II receptor antagonist, widely used in treatment for hypertension. Immunohistochemical stainings for TGF-beta 1, bax, caspase-3 and WT-1 were performed. The microalbuminuria levels of the Irbesartan-treated diabetic group were lower than those of the untreated diabetic group (P < 0.01). The immunostaining of TGF-beta 1, bax and caspase-3 was decreased in glomeruli of the Irbesartan-treated diabetic group compared to the untreated diabetic group. WT-1 immunopositive podocyte numbers were found to be significantly lower in the untreated diabetic group than in the other groups (P < 0.01). In the Irbesartan-treated diabetic group, the WT-1 immunopositive cell numbers were higher compared to the untreated diabetic group (P < 0.01). We conclude that the decrease in the number of podocytes is an early marker of diabetic nephropathy. AT1 receptor blocker has renoprotective effects on the regulation of renal hemodynamics and on the control of tissue damage by preventing podocyte loss, which leads to decrease of bax and caspase-3 expressions of apoptosis related proteins, and may prevent glomerular cell apoptosis via angiotensin II. (C) 2011 Elsevier GmbH. All rights reserved