The Renal and Cardio Protective Effects of Aliskiren and Pentoxifylline Alone and in Combination on Streptozotocin Induced Diabetic Rats

Background/Aims: The aim of the present study is to investigate the renoprotective and cardioprotective effect of aliskiren and pentoxifylline, alone and in combination, on streptozotocin (STZ) induced diabetic rats.

Methods: Fifty male Sprague Dawley rats were divided into 5 groups of 10 rats each, namely the control (Group I), diabetes (Group II), diabetic treated with aliskiren (Group III), diabetic treated with pentoxifylline (Group IV), and diabetic treated with aliskiren-pentoxifylline combination (Group V). Aliskiren (10 mg/kg/day) and pentoxifylline (55 mg/kg/ day) were given by oral-gavage once daily for 8 weeks. Renal function, oxidative stress parameters, immunohistochemical detection for transforming growth factor β, and kidney and heart histology were determined.

Results: Serum urea and creatinine reduced significantly in the three treated groups, Heart reduced glutathione (GSH) increased significantly only in aliskiren-pentoxifylline treated group, while kidney GSH increased significantly in the three treated groups. Kidney malondialdehyde (MDA) reduced significantly in the three treated groups, while heart MDA reduced significantly only in aliskiren-pentoxifylline treated group. No significant changes were detected in heart nitric oxide in all treated groups, while kidney nitric oxide reduced significantly in the aliskiren alone and aliskiren-pentoxifylline treated groups. Our results show that heart tumor necrosis factor alpha (TNF-α) reduced significantly only in the aliskiren-pentoxifylline treated group. On the other hand, kidney TNF-α reduced significantly in the pentoxifylline alone and aliskiren-pentoxifylline treated groups. Immunohistochemical detection of transforming growth factor β (TGF-β) in kidney and heart sections shows positive TGF-β and a high intensity of staining in the diabetic group, while it shows only mild to moderate staining in the three treated groups. Histopathological examination of kidney and heart sections shows more improvement in the aliskiren-pentoxifylline combination therapy than aliskiren and pentoxifylline monotherapy.

Conclusion: Combining aliskiren with pentoxifylline provided a greater reduction in heart and kidney damage than either drug alone in STZ induced diabetic rats.