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Sildenafil, a phosphodiesterase type 5 inhibitor, attenuates diabetic nephropathy in STZ-induced diabetic rats

  • Alok Shiomurti Tripathi EMAIL logo , Papiya Mitra Mazumder and Anil Vilasrao Chandewar
Published/Copyright: August 21, 2015

Abstract

Background: The present study evaluates the possible mechanism of sildenafil citrate (SIL) for the attenuation of renal failure in diabetic nephropathic (DN) animals.

Methods: Diabetic nephropathy was induced by a single dose of streptozotocin (STZ) (60 mg/kg, i.p.) and confirmed by assessing the blood and urine biochemical parameters on the 28th day of its induction. The selected DN animals were treated with glimepiride (0.5 mg/kg, p.o.) and SIL (2.5 mg/kg, p.o.) for a period of 6 weeks. Biochemical parameters in blood and urine were estimated after the 29th and 70th day of the protocol for the estimation of the effect of SIL.

Result: There were significant alterations in the blood and urine biochemical parameters in STZ-treated groups which confirmed DN. There was a significant decrease in the triglyceride level in the SIL-only-treated group on the 70th day of the protocol. The histopathology study also suggested that SIL treatment results in the improvement in the podocyte count in DN animals.

Conclusions: The present study concludes that SIL improves the renal function by decreasing the triglyceride level and improving the podocyte count in DN animals.


Corresponding author: Alok Shiomurti Tripathi, Department of Pharmacology, P. Wadhwani College of Pharmacy, Yavatmal-445001, Maharashtra, India; and Birla Institute of Technology, Department of Pharmaceutical Sciences, Mesra, Ranchi, Jharkhand, India, Phone: +91-7588891155, E-mail:

References

1. Foley RN, Collins AJ. End-stage renal disease in the United States: an update from the United States renal data system. J Am Soc Nephrol 2007;18:2644–8.10.1681/ASN.2007020220Search in Google Scholar

2. Musselman DL, Betan E, Larsen H, Phillips LS. Relationship of depression to diabetes types 1 and 2: epidemiology, biology, and treatment. Biol Psychiatr 2003;54:317–29.10.1016/S0006-3223(03)00569-9Search in Google Scholar

3. Buse JB, Ginsberg HN, Bakris GL, Clark NG, Costa F, Eckel R, et al. Primary prevention of cardiovascular diseases in people with diabetes mellitus a scientific statement from the American heart association and the American diabetes association. Diabetes Care 2007;30:162–72.10.2337/dc07-9917Search in Google Scholar PubMed

4. Viberti G. Thiazolidinediones – benefits on microvascular complications of type 2 diabetes. J Diabetes Complications 2005;19:168–77.10.1016/j.jdiacomp.2004.04.001Search in Google Scholar PubMed

5. Forbes J, Fukami K, Cooper M. Diabetic nephropathy: where hemodynamics meets metabolism. Exp Clin Endocrinol Diabetes 2007;115:69–84.10.1055/s-2007-949721Search in Google Scholar PubMed

6. Giunti S, Barit D, Cooper ME. Mechanisms of diabetic nephropathy role of hypertension. Hypertension 2006;48:519–26.10.1161/01.HYP.0000240331.32352.0cSearch in Google Scholar PubMed

7. Zalba G, Beaumont FJ, San José G, Fortuño A, Fortuño MA, Díez J. Is the balance between nitric oxide and superoxide altered in spontaneously hypertensive rats with endothelial dysfunction? Nephrol Dial Transplant 2001;16:2–5.10.1093/ndt/16.suppl_1.2Search in Google Scholar PubMed

8. Bredt D, Snyder S. Nitric oxide: a physiologic messenger molecule. Annu Rev Biochem 1994;63:175–95.10.1146/annurev.bi.63.070194.001135Search in Google Scholar PubMed

9. Yan C, Kim D, Aizawa T, Berk BC. Functional interplay between angiotensin II and nitric oxide cyclic GMP as a key mediator. Arterioscler Thromb Vasc Biol 2003;23:26–36.10.1161/01.ATV.0000046231.17365.9DSearch in Google Scholar PubMed

10. Firoozi F, Longhurst PA, White MD. In vivo and in vitro response of corpus cavernosum to phosphodiesterase‐5 inhibition in the hypercholesterolaemic rabbit. BJU Int 2005;96:164–8.10.1111/j.1464-410X.2005.05588.xSearch in Google Scholar PubMed

11. Dousa TP. Cyclic-3′,5′-nucleotide phosphodiesterase isozymes in cell biology and pathophysiology of the kidney. Kidney Int 1999;55:29–62.10.1046/j.1523-1755.1999.00233.xSearch in Google Scholar

12. Kuno Y, Iyoda M, Shibata T, Hirai Y, Akizawa T. Sildenafil, a phosphodiesterase type 5 inhibitor, attenuates diabetic nephropathy in non-insulin-dependent Otsuka Long-Evans Tokushima Fatty rats. Br J Pharmacol 2011;169:1389–400.10.1111/j.1476-5381.2010.01149.xSearch in Google Scholar

13. Saisho K, Scott K, Morimoto S, Nakahara Y. Extraction and determination of sildenafil (Viagra) and its N-desmethyl metabolite in rat and human hair by GC-MS. Biol Pharm Bull 2001;24:1384–8.10.1248/bpb.24.1384Search in Google Scholar

14. Berzas Nevado J, Rodrıguez Flores J, Castañeda Peñalvo G, Rodrı́guez Fariñas N. Determination of sildenafil citrate and its main metabolite by sample stacking with polarity switching using micellar electrokinetic chromatography. J Chromatogr A 2002;953:279–86.10.1016/S0021-9673(02)00131-0Search in Google Scholar

15. Chen HC, Guh JY, Chang JM, Hsich MC, Shin SJ, Lai YH. Role of lipid control in diabetic nephropathy. Kidney Int Suppl 2005;67:S60–2.10.1111/j.1523-1755.2005.09415.xSearch in Google Scholar PubMed

16. Ruan XZ, Varghese Z, Moorhead JF. Inflammation modifies lipid mediated renal injury. Nephrol Dial Transplant 2003;18:27–32.10.1093/ndt/18.1.27Search in Google Scholar PubMed

17. Eid AA, Gorin Y, Fagg BM, Maalouf R, Barnes JL, Block K, et al. Mechanisms of podocyte injury in diabetes: role of cytochrome P450 and NADPH oxidases. Diabetes 2009;58:1201–11.10.2337/db08-1536Search in Google Scholar PubMed PubMed Central

18. Jim B, Ghanta M, Qipo A, Fan Y, Chuang PY, Cohen HW, et al. Dysregulated nephrin in diabetic nephropathy of type 2 diabetes: a cross sectional study. PLoS One 2012;7:e36041.10.1371/journal.pone.0036041Search in Google Scholar PubMed PubMed Central

Received: 2015-3-31
Accepted: 2015-7-15
Published Online: 2015-8-21
Published in Print: 2016-1-1

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