• Logo
  • SBMUJournals

The Association of Phosphodiesterase 5 Inhibitor on Ischemia-Reperfusion Induced Kidney Injury in Rats

Jong Kil Nam, Jung Hee Kim, Sung Woo Park, Moon Kee Chung
152

Views


Abstract

Purpose: Ischemia-reperfusion (IR) causes various damage in renal tissues. The aim of the present study was to evaluate the renoprotective effect of phosphodiesterase 5 inhibitor (PDE5I) on IR induced renal injury in a rat model.

Materials and Methods: Thirty adult male, 12-week-old, Sprague-Dawley rats were divided into three groups. Renal IR injury was induced by occlusion of the bilateral renal pedicle for 45 min followed by reperfusion for 24 h. The rats were sacrificed for collecting blood and tissue specimens. IR rats were administered daily oral Tadalafil (group I) or no pills (group II), while sham-operated animals were treated with no pills (sham group). The pill was diluted with distilled water and administered to rats for 15 days, orally. Renal histopathology, function, pro-inflammatory and inflammatory cytokines and mediators were assessed by serum creatinine, western blot assay and immunohistochemistry.

Results: Compared with sham group, rats that underwent renal IR operation exhibited a significant increase in concentration in serum creatinine (p< .01) and tissue pro-inflammatory and inflammatory mediators. In group I, however, tadalafil significantly suppressed elevation of the serum creatinine and increased the levels of endothelial nitric oxide synthase and decreased the level of intercellular adhesion molecule-1 (ICAM-1) than group II (p< .05). Moreover, tadalafil prevented IR-induced expression of pro-inflammatory mediators such as monocyte chemotactic protein-1 (MCP-1) (p< .05).

Conclusion: Tadalafil significantly promotes functional recovery after renal IR injury and effectively inhibits the induction of pro-inflammatory and inflammatory mediators. The results substantiate Tadalafil as a protective agent against IR-induced renal injury.


References

López-Neblina F, Paez AJ, Toledo AH, Toledo-Pereyra LH. Role of nitric oxide in ischemia/reperfusion of the rat kidney. Circ Shock. 1994;44:91-5.

Elahi MM, Kong YX, Matata BM. Oxidative stress as a mediator of cardiovascular disease. Oxid Med Cell Longev. 2009;2:259-69.

Snoeijs MG, Vink H, Voesten N, et al. Acute ischemic injury to the renal microvasculature in human kidney transplantation. Am J Physiol Renal Physiol. 2010;299:F1134-40.

Sharfuddin AA, Molitoris BA. Pathophysiology of ischemic acute kidney injury. Nat Rev Nephrol. 2011;7:189-200.

Patschan D, Patschan S, Müller GA. Inflammation and microvasculopathy in renal ischemia reperfusion injury. J Transplant. 2012;2012:764154.

Qiao X, Li RS, Li H, et al. Intermedin protects against renal ischemia-reperfusion injury by inhibition of oxidative stress. Am J Physiol Renal Physiol. 2013;304:F112-9.

Yokoyama O, Igawa Y, Takeda M, Yamaguchi T, Murakami M, Viktrup L. Tadalafil for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a review of clinical data in Asian men and an update on the mechanism of action. Ther Adv Urol. 2015;7:249-64.

Kukreja RC. Sildenafil and cardioprotection. Curr Pharm Des. 2013;19:6842-7.

Küçük A, Yucel M, Erkasap N, et al. The effects of PDE5 inhibitory drugs on renal ischemia/reperfusion injury in rats. Mol Biol Rep. 2012;39:9775-82.

Vignozzi L, Filippi S, Morelli A, et al. Effect of chronic tadalafil administration on penile hypoxia induced by cavernous neurotomy in the rat. J Sex Med. 2006;3:419-31.

Esposito E, Mondello S, Di Paola R, et al. Glutamine contributes to ameliorate inflammation after renal ischemia/reperfusion injury in rats. Naunyn Schmiedebergs Arch Pharmacol. 2011;383:493-508.

Chatterjee PK, di Villa Bianca RD, Sivarajah A, McDonald MC, Cuzzocrea S, Thiemermann C. Pyrrolidine dithiocarbamate reduces renal dysfunction and injury caused by ischemia/reperfusion of the rat kidney. Eur J Pharmacol. 2003;482:271-80.

Guan Z, Miller SB, Greenwald JE. Zaprinast accelerates recovery from established acute renal failure in the rat. Kidney Int. 1995;47:1569-75.

Shi SR, Key ME, Kalra KL. Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem. 1991;39:741-8.

Robertson D, Savage K, Reis-Filho JS, Isacke CM. Multiple immunofluorescence labelling of formalin-fixed paraffin-embedded (FFPE) tissue. BMC Cell Biol. 2008;9:13.

Mahmood T, Yang P-C. Western Blot: Technique, Theory, and Trouble Shooting. N Am J Med Sci. 2012 Sep;4(9):429-34.

Alegria-Schaffer A, Lodge A, Vattem K. Performing and optimizing Western blots with an emphasis on chemiluminescent detection. Methods Enzymol. 2009;463:573-99.

Dulabon LM, Kaouk JH, Haber GP, et al. Multi-institutional analysis of robotic partial nephrectomy for hilar versus nonhilar lesions in 446 consecutive cases. Eur Urol. 2011;59:325-30.

Novick AC. Renal hypothermia: in vivo and ex vivo. Urol Clin North Am. 1983;10:637-44.

Weinbroum AA. Methylene blue attenuates pancreas ischemia-reperfusion (IR)-induced lung injury: a dose response study in a rat model. J Gastrointest Surg. 2009;13:1683-91.

Sener G, Sehirli AO, Keyer-Uysal M, Arbak S, Ersoy Y, Yeğen BC.The protective effect of melatonin on renal ischemia-reperfusion injury in the rat. J Pineal Res. 2002;32:120-6.

Rusai K, Prokai A, Juanxing C, et al. Dexamethasone protects from renal ischemia/reperfusion injury: a possible association with SGK-1. Acta Physiol Hung. 2013;100:173-85.

Cámara-Lemarroy CR, Guzmán-de la Garza FJ, Alarcón-Galván G, Cordero-Pérez P, Fernández-Garza NE. Effect of sulfasalazine on renal ischemia/reperfusion injury in rats. Ren Fail. 2009;31:822-8.

Hosseini F, Naseri MK, Badavi M, Ghaffari MA, Shahbazian H, Rashidi I. Protective effect of beta carotene pretreatment on renal ischemia/reperfusion injury in rat. Pak J Biol Sci. 2009;12:1140-5.

Schwarz ER, Kapur V, Rodriguez J, Rastogi S, Rosanio S. The effects of chronic phosphodiesterase-5 inhibitor use on different organ systems. Int J Impot Res. 2007;19:139-48.

Carden DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol.2000;190:255-66.

Yamasowa H, Shimizu S, Inoue T, Takaoka M, Matsumura Y. Endothelial nitric oxide contributes to the renal protective effects of ischemic preconditioning. J Pharmacol Exp Ther. 2005;312:153-9.

Yamashita J, Ogata M, Itoh M, et al. Role of nitric oxide in the renal protective effects of ischemic preconditioning. J Cardiovasc Pharmacol. 2003;42:419-27.

Elrod JW, Greer JJ, Lefer DJ. Sildenafil-mediated acute cardioprotection is independent of the NO/cGMP pathway. Am J Physiol Heart Circ Physiol. 2007;292:H342-7.

Etienne-Manneville S, Chaverot N, Strosberg AD, Couraud PO. ICAM-1-coupled signaling pathways in astrocytes converge to cyclic AMP response element-binding protein phosphorylation and TNF-alpha secretion. J Immunol. 1999;163:668-74.

Ichikawa H, Flores S, Kvietys PR, et al. Molecular mechanisms of anoxia/reoxygenation-induced neutrophil adherence to cultured endothelial cells. Circ Res. 1997;81:922-31.

Xia M, Sui Z. Recent developments in CCR2 antagonists. Expert Opin Ther Pat. 2009;19:295-303.

Lloyd CM, Minto AW, Dorf ME, et al. RANTES and monocyte chemoattractant protein-1 (MCP-1) play an important role in the inflammatory phase of crescentic nephritis, but only MCP-1 is involved in crescent formation and interstitial fibrosis. J Exp Med. 1997;185:1371-80.




DOI: http://dx.doi.org/10.22037/uj.v0i0.4173

Refbacks

  • There are currently no refbacks.