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Oxidative Medicine and Cellular Longevity
Volume 2014, Article ID 161942, 10 pages
http://dx.doi.org/10.1155/2014/161942
Research Article

Sildenafil Attenuates Hepatocellular Injury after Liver Ischemia Reperfusion in Rats: A Preliminary Study

1Experimental Surgical Unit, Aretaieion University Hospital, 11528 Athens, Greece
2Second Department of Surgery, Aretaieion University Hospital, 11528 Athens, Greece
3Pathology Department, Sismanoglio General Hospital, 15126 Athens, Greece
4Department of Anesthesiology, Penteli Pediatric Hospital, 15236 Athens, Greece
5Fourth Department of Surgery, Attikon University Hospital, 12462 Athens, Greece
6Department of Anesthesiology, Aretaieion University Hospital, 11528 Athens, Greece

Received 28 March 2014; Revised 16 May 2014; Accepted 19 May 2014; Published 4 June 2014

Academic Editor: Dimitrios Tsikas

Copyright © 2014 Spyridon Savvanis et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. N. N. Rahbari, M. N. Wente, P. Schemmer et al., “Systematic review and meta-analysis of the effect of portal triad clamping on outcome after hepatic resection,” British Journal of Surgery, vol. 95, no. 4, pp. 424–432, 2008. View at Publisher · View at Google Scholar · View at Scopus
  2. V. Smyrniotis, C. Farantos, G. Kostopanagiotou, and N. Arkadopoulos, “Vascular control during hepatectomy: review of methods and results,” World Journal of Surgery, vol. 29, no. 11, pp. 1384–1396, 2005. View at Publisher · View at Google Scholar · View at Scopus
  3. F. Serracino-Inglott, N. A. Habib, and R. T. Mathie, “Hepatic ischemia-reperfusion injury,” American Journal of Surgery, vol. 181, no. 2, pp. 160–166, 2001. View at Publisher · View at Google Scholar · View at Scopus
  4. Y. Zhai, H. Petrowsky, J. C. Hong, R. W. Busuttil, and J. W. Kupiec-Weglinski, “Ischaemia-reperfusion injury in liver transplantation-from bench to bedside,” Nature Reviews Gastroenterology and Hepatology, vol. 10, no. 2, pp. 79–89, 2013. View at Publisher · View at Google Scholar · View at Scopus
  5. D. Papadopoulos, T. Siempis, E. Theodorakou, and G. Tsoulfas, “Hepatic ischemia and reperfusion injury and trauma: current concepts,” Archives of Trauma Research, vol. 2, pp. 63–70, 2013. View at Google Scholar
  6. H. A. Arab, F. Sasani, M. H. Rafiee, A. Fatemi, and A. Javaheri, “Histological and biochemical alterations in early-stage lobar ischemia-reperfusion in rat liver,” World Journal of Gastroenterology, vol. 15, no. 16, pp. 1951–1957, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. H. Jaeschke, “Reactive oxygen and mechanisms of inflammatory liver injury: present concepts,” Journal of Gastroenterology and Hepatology, vol. 26, supplement 1, pp. 173–179, 2011. View at Publisher · View at Google Scholar · View at Scopus
  8. B. Vollmar, J. Glasz, R. Leiderer, S. Post, and M. D. Menger, “Hepatic microcirculatory perfusion failure is a determinant of liver dysfunction in warm ischemia-reperfusion,” The American Journal of Pathology, vol. 145, no. 6, pp. 1421–1431, 1994. View at Google Scholar · View at Scopus
  9. H. Jaeschke, “Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning,” The American Journal of Physiology—Gastrointestinal and Liver Physiology, vol. 284, no. 1, pp. G15–G26, 2003. View at Google Scholar · View at Scopus
  10. M. D. Menger, S. Richter, J. Yamauchi, and B. Vollmar, “Role of microcirculation in hepatic ischemia/reperfusion injury,” Hepato-Gastroenterology, vol. 46, no. 2, pp. 1452–1457, 1999. View at Google Scholar · View at Scopus
  11. H. A. Rüdiger, R. Graf, and P. Clavien, “Liver ischemia: apoptosis as a central mechanism of injury,” Journal of Investigative Surgery, vol. 16, no. 3, pp. 149–159, 2003. View at Google Scholar · View at Scopus
  12. V. Kohli, M. Selzner, J. F. Madden, R. C. Bentley, and P. Clavien, “Endothelial cell and hepatocyte deaths occur by apoptosis after ischemia-reperfusion injury in the rat liver,” Transplantation, vol. 67, no. 8, pp. 1099–1105, 1999. View at Publisher · View at Google Scholar · View at Scopus
  13. C. Nastos, K. Kalimeris, N. Papoutsidakis et al., “Global consequences of liver ischemia/reperfusion injury,” Oxidative Medicine and Cellular Longevity, vol. 2014, Article ID 906965, 13 pages, 2014. View at Publisher · View at Google Scholar
  14. F. Serracino-Inglott, I. T. Virlos, N. A. Habib, R. C. N. Williamson, and R. T. Mathie, “Differential nitric oxide synthase expression during hepaticischemia-reperfusion,” American Journal of Surgery, vol. 185, no. 6, pp. 589–595, 2003. View at Publisher · View at Google Scholar · View at Scopus
  15. A. Siriussawakul, A. Zaky, and J. D. Lang, “Role of nitric oxide in hepatic ischemia-reperfusion injury,” World Journal of Gastroenterology, vol. 16, no. 48, pp. 6079–6086, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. R. C. Kukreja, F. Salloum, A. Das et al., “Pharmacological preconditioning with sildenafil: basic mechanisms and clinical implications,” Vascular Pharmacology, vol. 42, no. 5-6, pp. 219–232, 2005. View at Publisher · View at Google Scholar · View at Scopus
  17. M. Abu-Amara, S. Y. Yang, A. Seifalian, B. Davidson, and B. Fuller, “The nitric oxide pathway—evidence and mechanisms for protection against liver ischaemia reperfusion injury,” Liver International, vol. 32, no. 4, pp. 531–543, 2012. View at Publisher · View at Google Scholar · View at Scopus
  18. L. Zhou and D. Zhu, “Neuronal nitric oxide synthase: structure, subcellular localization, regulation, and clinical implications,” Nitric Oxide—Biology and Chemistry, vol. 20, no. 4, pp. 223–230, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. M. S. Chintala, V. Bernardino, and P. J. S. Chiu, “Cyclic GMP but not cyclic AMP prevents renal platelet accumulation after ischemia-reperfusion in anesthetized rats,” Journal of Pharmacology and Experimental Therapeutics, vol. 271, no. 3, pp. 1203–1208, 1994. View at Google Scholar · View at Scopus
  20. H. Yaseen, M. Sarwich, and H. Hamdy, “Is sildenafil an effective therapy in the management of persistent pulmonary hypertension?” Journal of Clinical Neonatology, vol. 1, pp. 171–175, 2012. View at Google Scholar
  21. P. Botha, G. A. MacGowan, and J. H. Dark, “Sildenafil citrate augments myocardial protection in heart transplantation,” Transplantation, vol. 89, no. 2, pp. 169–177, 2010. View at Publisher · View at Google Scholar · View at Scopus
  22. P. Shih, C. Cheng, H. Li et al., “Pretreatment with sildenafil alleviates early lung ischemia-reperfusion injury in a rat model,” Journal of Surgical Research, vol. 185, pp. e77–e83, 2013. View at Publisher · View at Google Scholar · View at Scopus
  23. D. E. Choi, J. Y. Jeong, B. J. Lim et al., “Pretreatment of sildenafil attenuates ischemia-reperfusion renal injury in rats,” The American Journal of Physiology—Renal Physiology, vol. 297, no. 2, pp. F362–F370, 2009. View at Publisher · View at Google Scholar · View at Scopus
  24. O. Ozdegirmenci, T. Kucukozkan, E. Akdag et al., “Effects of sildenafil and tadalafil on ischemia/reperfusion injury in fetal rat brain,” Journal of Maternal-Fetal and Neonatal Medicine, vol. 24, no. 2, pp. 317–323, 2011. View at Publisher · View at Google Scholar · View at Scopus
  25. A. A. Aldashev, B. K. Kojonazarov, T. A. Amatov et al., “Phosphodiesterase type 5 and high altitude pulmonary hypertension,” Thorax, vol. 60, no. 8, pp. 683–687, 2005. View at Publisher · View at Google Scholar · View at Scopus
  26. C. A. Dias-Junior, D. C. Souza-Costa, T. Zerbini, J. B. T. da Rocha, R. F. Gerlach, and J. E. Tanus-Santos, “The effect of sildenafil on pulmonary embolism-induced oxidative stress and pulmonary hypertension,” Anesthesia and Analgesia, vol. 101, no. 1, pp. 115–120, 2005. View at Publisher · View at Google Scholar · View at Scopus
  27. R. L. Keller, S. E. G. Hamrick, J. A. Kitterman, J. R. Fineman, and S. Hawgood, “Treatment of rebound and chronic pulmonary hypertension with oral sildenafil in an infant with congenital diaphragmatic hernia,” Pediatric Critical Care Medicine, vol. 5, no. 2, pp. 184–187, 2004. View at Google Scholar · View at Scopus
  28. D. L. Diesen and P. C. Kuo, “Nitric oxide and redox regulation in the liver: part II. Redox biology in pathologic hepatocytes and implications for intervention,” Journal of Surgical Research, vol. 167, no. 1, pp. 96–112, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. C. Hsu, J. Wang, C. Liu, and L. Chen, “Kupffer cells protect liver from ischemia-reperfusion injury by an inducible nitric oxide synthase-dependent mechanism,” Shock, vol. 17, no. 4, pp. 280–285, 2002. View at Google Scholar · View at Scopus
  30. V. G. Lee, M. L. Johnson, J. Baust, V. E. Laubach, S. C. Watkins, and T. R. Billiar, “The roles of iNOS in liver ischemia-reperfusion injury,” Shock, vol. 16, no. 5, pp. 355–360, 2001. View at Google Scholar · View at Scopus
  31. T. Chen, R. Zamora, B. Zuckerbraun, and T. R. Billiar, “Role of nitric oxide in liver injury,” Current Molecular Medicine, vol. 3, no. 6, pp. 519–526, 2003. View at Publisher · View at Google Scholar · View at Scopus
  32. C. Cottart, L. Do, M. Blanc et al., “Hepatoprotective effect of endogenous nitric oxide during ischemia- reperfusion in the rat,” Hepatology, vol. 29, no. 3, pp. 809–813, 1999. View at Google Scholar · View at Scopus
  33. G. Datta, B. J. Fuller, and B. R. Davidson, “Molecular mechanisms of liver ischemia reperfusion injury: insights from transgenic knockout models,” World Journal of Gastroenterology, vol. 19, no. 11, pp. 1683–1698, 2013. View at Publisher · View at Google Scholar · View at Scopus
  34. I. N. Hines, S. Kawachi, H. Harada et al., “Role of nitric oxide in liver ischemia and reperfusion injury,” Molecular and Cellular Biochemistry, vol. 234-235, no. 1-2, pp. 229–237, 2002. View at Publisher · View at Google Scholar · View at Scopus
  35. Y. Abe, I. N. Hines, G. Zibari et al., “Mouse model of liver ischemia and reperfusion injury: method for studying reactive oxygen and nitrogen metabolites in vivo,” Free Radical Biology and Medicine, vol. 46, no. 1, pp. 1–7, 2009. View at Publisher · View at Google Scholar · View at Scopus
  36. M. R. Duranski, J. W. Elrod, J. W. Calvert, N. S. Bryan, M. Feelisch, and D. J. Lefer, “Genetic overexpression of eNOS attenuates hepatic ischemia-reperfusion injury,” The American Journal of Physiology—Heart and Circulatory Physiology, vol. 291, no. 6, pp. H2980–H2986, 2006. View at Publisher · View at Google Scholar · View at Scopus
  37. T. K. Gupta, M. Toruner, M. K. Chung, and R. J. Groszmann, “Endothelial dysfunction and decreased production of nitric oxide in the intrahepatic microcirculation of cirrhotic rats,” Hepatology, vol. 28, no. 4 I, pp. 926–931, 1998. View at Publisher · View at Google Scholar · View at Scopus
  38. M. R. Loureiro-Silva, Y. Iwakiri, J. G. Abraldes, O. Haq, and R. J. Groszmann, “Increased phosphodiesterase-5 expression is involved in the decreased vasodilator response to nitric oxide in cirrhotic rat livers,” Journal of Hepatology, vol. 44, no. 5, pp. 886–893, 2006. View at Publisher · View at Google Scholar · View at Scopus
  39. G. M. Hur, Y. S. Ryu, H. Y. Yun et al., “Hepatic ischemia/reperfusion in rats induces iNOS gene transcription by activation of NF-κB,” Biochemical and Biophysical Research Communications, vol. 261, no. 3, pp. 917–922, 1999. View at Publisher · View at Google Scholar · View at Scopus
  40. J. S. Beckman, T. W. Beckman, J. Chen, P. A. Marshall, and B. A. Freeman, “Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide,” Proceedings of the National Academy of Sciences of the United States of America, vol. 87, no. 4, pp. 1620–1624, 1990. View at Google Scholar · View at Scopus
  41. F. Salloum, C. Yin, L. Xi, and R. C. Kukreja, “Sildenafil induces delayed preconditioning through inducible nitric oxide synthase-dependent pathway in mouse heart,” Circulation Research, vol. 92, no. 6, pp. 595–597, 2003. View at Publisher · View at Google Scholar · View at Scopus
  42. A. Das, L. Xi, and R. C. Kukreja, “Phosphodiesterase-5 inhibitor sildenafil preconditions adult cardiac myocytes against necrosis and apoptosis: essential role of nitric oxide signaling,” The Journal of Biological Chemistry, vol. 280, no. 13, pp. 12944–12955, 2005. View at Publisher · View at Google Scholar · View at Scopus
  43. A. Das, R. Ockaili, F. Salloum, and R. C. Kukreja, “Protein kinase C plays an essential role in sildenafil-induced cardioprotection in rabbits,” The American Journal of Physiology—Heart and Circulatory Physiology, vol. 286, no. 4, pp. H1455–H1460, 2004. View at Publisher · View at Google Scholar · View at Scopus
  44. R. Ockaili, F. Salloum, J. Hawkins, and R. C. Kukreja, “Sildenafil (Viagra) induces powerful cardioprotective effect via opening of mitochondrial KATP channels in rabbits,” The American Journal of Physiology—Heart and Circulatory Physiology, vol. 283, no. 3, pp. H1263–H1269, 2002. View at Google Scholar · View at Scopus
  45. J. W. Elrod, J. J. M. Greer, and D. J. Lefer, “Sildenafil-mediated acute cardioprotection is independent of the NO/cGMP pathway,” The American Journal of Physiology—Heart and Circulatory Physiology, vol. 292, no. 1, pp. H342–H347, 2007. View at Publisher · View at Google Scholar · View at Scopus
  46. J. S. Beckman and W. H. Koppenol, “Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and the ugly,” The American Journal of Physiology—Cell Physiology, vol. 271, no. 5, pp. C1424–C1437, 1996. View at Google Scholar · View at Scopus
  47. R. Channick, I. Preston, and J. R. Klinger, “Oral therapies for pulmonary hypertension: endothelin receptor antagonists and phosphodiesterase-5 inhibitors,” Clinics in Chest Medicine, vol. 34, pp. 811–824, 2013. View at Google Scholar
  48. H. S. Shin, S. K. Bae, and M. G. Lee, “Pharmacokinetics of sildenafil after intravenous and oral administration in rats: hepatic and intestinal first-pass effects,” International Journal of Pharmaceutics, vol. 320, no. 1-2, pp. 64–70, 2006. View at Publisher · View at Google Scholar · View at Scopus
  49. K. Lee, Y. Yang, Y. Wang et al., “Acute administration of sildenafil enhances hepatic cyclic guanosine monophosphate production and reduces hepatic sinusoid resistance in cirrhotic patients,” Hepatology Research, vol. 38, no. 12, pp. 1186–1193, 2008. View at Publisher · View at Google Scholar · View at Scopus
  50. K. Lee, Y. Yang, Y. Huang et al., “Administration of a low dose of sildenafil for 1 week decreases intrahepatic resistance in rats with biliary cirrhosis: the role of NO bioavailability,” Clinical Science, vol. 119, no. 1, pp. 45–55, 2010. View at Publisher · View at Google Scholar · View at Scopus
  51. N. Hori, R. Wiest, and R. J. Groszmann, “Enhanced release of nitric oxide in response to changes in flow and shear stress in the superior mesenteric arteries of portal hypertensive rats,” Hepatology, vol. 28, no. 6, pp. 1467–1473, 1998. View at Google Scholar · View at Scopus
  52. C. Lam, T. E. Peterson, D. M. Richardson et al., “Increased blood flow causes coordinated upregulation of arterial eNOS and biosynthesis of tetrahydrobiopterin,” The American Journal of Physiology—Heart and Circulatory Physiology, vol. 290, no. 2, pp. H786–H793, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. B. Tantini, A. Manes, E. Fiumana et al., “Antiproliferative effect of sildenafil on human pulmonary artery smooth muscle cells,” Basic Research in Cardiology, vol. 100, no. 2, pp. 131–138, 2005. View at Publisher · View at Google Scholar · View at Scopus
  54. B. Rosengarten, R. T. Schermuly, R. Voswinckel et al., “Sildenafil improves dynamic vascular function in the brain: studies in patients with pulmonary hypertension,” Cerebrovascular Diseases, vol. 21, no. 3, pp. 194–200, 2006. View at Publisher · View at Google Scholar · View at Scopus
  55. J. Li, P. Fu, M. Deleon, B. A. French, and S. W. French, “The effect of Viagra (sildenafil citrate) on liver injury caused by chronic ethanol intragastric feeding in rats,” Experimental and Molecular Pathology, vol. 78, no. 2, pp. 101–108, 2005. View at Publisher · View at Google Scholar · View at Scopus
  56. S. Yardimci, E. B. Bostanci, I. Ozer et al., “Sildenafil accelerates liver regeneration after partial hepatectomy in rats,” Transplantation Proceedings, vol. 44, no. 6, pp. 1747–1750, 2012. View at Publisher · View at Google Scholar · View at Scopus
  57. M. Ekor, A. O. Odewabi, O. E. Kale, T. O. Bamidele, O. A. Adesanoye, and E. O. Farombi, “Modulation of paracetamol-induced hepatotoxicity by phosphodiesterase isozyme inhibition in rats: a preliminary study,” Journal of Basic and Clinical Physiology and Pharmacology, vol. 24, no. 1, pp. 73–79, 2013. View at Google Scholar · View at Scopus
  58. K. Suzuki, H. Ota, S. Sasagawa, T. Sakatani, and T. Fujikura, “Assay method for myeloperoxidase in human polymorphonuclear leukocytes,” Analytical Biochemistry, vol. 132, no. 2, pp. 345–352, 1983. View at Google Scholar · View at Scopus
  59. J. E. Krawisz, P. Sharon, and W. F. Stenson, “Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models,” Gastroenterology, vol. 87, no. 6, pp. 1344–1350, 1984. View at Google Scholar · View at Scopus
  60. S. Suzuki, L. H. Toledo-Pereyra, F. J. Rodriguez, and D. Cejalvo, “Neutrophil infiltration as an important factor in liver ischemia and reperfusion injury: modulating effects of FK506 and cyclosporine,” Transplantation, vol. 55, no. 6, pp. 1265–1272, 1993. View at Google Scholar · View at Scopus
  61. P. R. Hansen, “Role of neutrophils in myocardial ischemia and reperfusion,” Circulation, vol. 91, no. 6, pp. 1872–1885, 1995. View at Google Scholar · View at Scopus
  62. S. S. Yadav, D. N. Howell, W. Gao, D. A. Steeber, R. C. Harland, and P. Clavien, “L-selectin and ICAM-1 mediate reperfusion injury and neutrophil adhesion in the warm ischemic mouse liver,” The American Journal of Physiology—Gastrointestinal and Liver Physiology, vol. 275, no. 6, pp. G1341–G1352, 1998. View at Google Scholar · View at Scopus
  63. H. Nakano, M. Kuzume, K. Namatame, M. Yamaguchi, and K. Kumada, “Efficacy of intraportal injection of anti-ICAM-1 monoclonal antibody against liver cell injury following warm ischemia in the rat,” American Journal of Surgery, vol. 170, no. 1, pp. 64–66, 1995. View at Publisher · View at Google Scholar · View at Scopus
  64. S. Marubayashi, Y. Oshiro, T. Maeda et al., “Protective effect of monoclonal antibodies to adhesion molecules on rat liver ischemia-reperfusion injury,” Surgery, vol. 122, no. 1, pp. 45–52, 1997. View at Publisher · View at Google Scholar · View at Scopus
  65. I. Kurose, R. Wolf, M. B. Grisham, and D. N. Granger, “Modulation of ischemia/reperfusion-induced microvascular dysfunction by nitric oxide,” Circulation Research, vol. 74, no. 3, pp. 376–382, 1994. View at Google Scholar · View at Scopus
  66. S. Kanwar and P. Kubes, “Nitric oxide is an antiadhesive molecule for leukocytes,” New Horizons: Science and Practice of Acute Medicine, vol. 3, no. 1, pp. 93–104, 1995. View at Google Scholar · View at Scopus
  67. J. Gaboury, R. C. Woodman, D. N. Granger, P. Reinhardt, and P. Kubes, “Nitric oxide prevents leukocyte adherence: role of superoxide,” The American Journal of Physiology—Heart and Circulatory Physiology, vol. 265, no. 3, pp. H862–H867, 1993. View at Google Scholar · View at Scopus
  68. W. Gao, R. C. Bentley, J. E. Madden, and P. Clavien, “Apoptosis of sinusoidal endothelial cells is a critical mechanism of preservation injury in rat liver transplantation,” Hepatology, vol. 27, no. 6, pp. 1652–1660, 1998. View at Publisher · View at Google Scholar · View at Scopus
  69. P. W. Fisher, F. Salloum, A. Das, H. Hyder, and R. C. Kukreja, “Phosphodiesterase-5 inhibition with sildenafil attenuates cardiomyocyte apoptosis and left ventricular dysfunction in a chronic model of doxorubicin cardiotoxicity,” Circulation, vol. 111, no. 13, pp. 1601–1610, 2005. View at Publisher · View at Google Scholar · View at Scopus
  70. F. N. Salloum, A. Abbate, A. Das et al., “Sildenafil (Viagra) attenuates ischemic cardiomyopathy and improves left ventricular function in mice,” The American Journal of Physiology—Heart and Circulatory Physiology, vol. 294, no. 3, pp. H1398–H1406, 2008. View at Publisher · View at Google Scholar · View at Scopus
  71. Y. Kim, R. V. Talanian, and T. R. Billiar, “Nitric oxide inhibits apoptosis by preventing increases in caspase-3- like activity via two distinct mechanisms,” The Journal of Biological Chemistry, vol. 272, no. 49, pp. 31138–31148, 1997. View at Publisher · View at Google Scholar · View at Scopus
  72. A. Rus, F. Molina, M. Á. Peinado, and M. L. del Moral, “Endothelial NOS-derived nitric oxide prevents injury resulting from reoxygenation in the hypoxic lung,” Free Radical Research, vol. 44, no. 9, pp. 1027–1035, 2010. View at Publisher · View at Google Scholar · View at Scopus
  73. M. Akao, A. Ohler, B. O'Rourke, and E. Marbán, “Mitochondrial ATP-sensitive potassium channels inhibit apoptosis induced by oxidative stress in cardiac cells,” Circulation Research, vol. 88, no. 12, pp. 1267–1275, 2001. View at Google Scholar · View at Scopus