Original Report: Laboratory Investigation

Effects of Sildenafil on Oxidative and Inflammatory Injuries of the Kidney in Streptozotocin-Induced Diabetic Rats
Kyung-Hwan Jeong^a, Tae-Won Lee^a, Chun-Gyoo Ihm^a, Sang-Ho Lee^a, Ju-Young Moon^a, Sung-Jig Lim^b

Departments of
^aNephrology and
^bPathology, School of Medicine, Kyung Hee University, Seoul, Korea

Address of Corresponding Author

Am J Nephrol 2009;29:274-282 (DOI: 10.1159/000158635)

  Key Words

• Diabetic nephropathy
• Inflammation
• Oxidative stress
• Sildenafil

  Abstract

Background: Oxidative stress and inflammation are implicated in the pathogenesis of diabetic nephropathy. Because sildenafil citrate (Viagra®) has variable cardiovascular benefits, including antioxidative and immunomodulating effects, we investigated its influence on oxidative stress and inflammation in diabetic rat kidney. Methods: Streptozotocin-induced diabetic rats received sildenafil (3 mg/kg/day in drinking water) or not (undosed water) for 8 weeks and were compared to age-matched nondiabetic animals. We evaluated 8-hydroxydeoxyguanosine (8-OHdG; for oxidative DNA damage), inducible nitric oxide synthase (iNOS) and nitrotyrosine (for excessive NO production and peroxynitrite formation), and representative chemoattractants [monocyte chemotactic protein-1, MCP-1; for inflammation and monocyte/macrophage infiltrations (ED-1)] in the kidney. Results: Sildenafil-treated rats had a lower kidney-to-body weight ratio than untreated diabetic rats. Urinary albumin excretion in diabetic rats decreased significantly after sildenafil treatment without changes in systolic blood pressure. Sildenafil-treated rats had significantly lower urinary and renal cortical 8-OHdG levels than the nonsildenafil group. Sildenafil administration significantly attenuated the increased renal nitrotyrosine protein expression, positive iNOS and ED-1 staining in glomeruli and tubulointerstitium, and nitrotyrosine staining in tubulointerstitium. Cortical MCP-1 RNA expression in the sildenafil group was significantly lower than in the nonsildenafil group. Conclusions: Sildenafil treatment may attenuate renal damage by ameliorating oxidative and inflammatory injuries in diabetic rats.

Copyright © 2008 S. Karger AG, Basel

  Author Contacts

Tae-Won Lee
Department of Nephrology, School of Medicine, Kyung Hee University
1, Hoegi-dong, Dongdaemun-ku
Seoul 130-701 (Korea)
Tel. +82 2 958 8200, Fax +82 2 968 1848, E-Mail wonkid@chollian.net

  Article Information

Received: May 10, 2008
Accepted: June 28, 2008
Published online: September 24, 2008
Number of Print Pages : 9
Number of Figures : 6, Number of Tables : 1, Number of References : 33