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Effects of papaverine in hepatic ischemia-reperfusion injury in rats

Year 2012, Volume: 11 Issue: 1, 2 - 6, 01.04.2012

Abstract

Background and Aims: The present study aimed to investigate the in volvement of the phosphodiesterase inhibitor and vasodilator papaverine in hepatic ischemia-reperfusion injury. Materials and Methods: The study was conducted in the Experimental Animals Laboratory of Dokuz Eylül University. Totally, 21 female Wistar albino rats were divided into three groups as: (1) Sham Group: the abdomen was surgically opened and closed without any surgical procedure. (2) Control Group: the hepatic portal triad was clipped with microvascular clips and 20 mg/kg normal saline was administered 30 minutes after the ischemia. (3) Experimental (Papaverine) Group: the portal triad was clipped as described above and 20 mg/kg papaverine was administered 30 minutes after the ischemia. Sixty-minutes of ischemia followed by 120 minutes of reperfusion were induced in Groups 2 and 3. Histopathological evaluation of the damage was performed according to Suzuki's scoring system. The sections were analyzed for hydropic swelling, granular degeneration, microvesicular vacuolization, macrovesicular vacuolization, and focal necrosis cord disorder in the parenchyma, for inflammation and fibrosis in the portal area, and for hyperemia in the sinusoids. Results: According to the statistical evaluation of our study, it was shown that ischemia-reperfusion injury was significantly reduced in the study group compared with the control in all parameters except focal necrosis and hydropic swelling. Conclusions: We concluded that papaverine may reduce damage in a hepatic ischemia-reperfusion model.

References

  • Chiappa AC, Makuuchi M, Zbar AP, et al. Protective effect of methylprednisolone and of intermittent hepatic pedicle clamping during liver vascular inflow occlusion in the rat. Hepatogastroente- rology 2004;51:1439-44.
  • Glanemann M, Strenziok R, Kuntze R, et al. Ischemic preconditio- ning and methylprednisolone both equally reduce hepatic ischemi- a/reperfusion injury. Surgery 2004;135:203-14.
  • Aslan A, Karagüzel G, Çelik M, et al. Pentoxifylline contributes to the hepatic cytoprotective process in rats undergoing hepatic isc- hemia and reperfusion injury. Eur Surg Res 2001;33:285-90.
  • Portakal O, Inal-Erden M. Effects of pentoxifylline and coenzyme Q10 in hepatic ischemia/reperfusion injury. Clin Biochem 1999;32: 461-6.
  • Vardareli E, Sarıçam T, Köken T, et al. The effect of alphatocophe
  • rol and pentoxyfilline on ischemia-reperfusion induced liver injury in rats. Hepatogastroenterology 1998;45:1505-8.
  • Yildirim S, Tok H, Koksal H, et al. Allopurinol plus pentoxifilline in
  • hepatic ischaemia/reperfusion injury. Asian J Surg 2002;25:149- 53.
  • Marteau P, Ballet F, Chazouilleres O, et al. Effect of vasodilators on
  • hepatic microcirculation in cirrhosis: a study in theisolated perfused rat liver. Hepatology 1989;9:820-3.
  • Chazouilleres O, Ballet F, Chretien Y, et al. Protective effect of va
  • sodilators on liver function after long hypothermic preservation: a study in the isolated perfused rat liver. Hepatology 1989;9:824-9.
  • Suzuki S, Nakamura S, Sakaguchi T, et al. Alteration of reticuloen
  • dothelial phagocytic function and tumor necrosis factor-alpha pro- duction after total hepatic ischemia. Transplantation 1997;64:821-7.
  • Boswell-Smith V, Spina D, Page CP. Phosphodiesterase inhibitors. Br J Pharmacol 2006;147 (Suppl 1):S252-7.
  • Krämer SC, Görich J, Oertel F, et al. Non-occlusive mesenteric isc- hemia. Rofo 2003;175:1177-83.
  • Robertazzi RR, Cunningham JN Jr. Intraoperative adjuncts of spinal cord protection. Semin Thorac Cardiovasc Surg 1998;10:29-34.
  • Liu X, Huang Y, Pokreisz P, et al. Nitric oxide inhalation improves microvascular flow and decreases infarction size after myocardial ischemia and reperfusion. J Am Coll Cardiol 2007;50:808-17.
  • Zhang ZG, Zhang QZ, Cheng YN, et al. Antagonistic effects of ul- tra-low-molecular-weight heparin against cerebral ischemia/reper- fusion injury in rats. Pharmacol Res 2007;56:350-5.
  • Bae EH, Lee KS, Lee J, et al. Effects of {alpha}-lipoic acid on ische- mia/reperfusion-induced renal dysfunction in rats. Am J Physiol Re- nal Physiol 2008;294:F272-80.
  • Guneli E, Cavdar Z, Islekel H, et al. N.Erythropoietin protects the in- testine against ischemia/ reperfusion injury in rats. Mol Med 2007;13:509-17.
  • Pekcetin C, Ergur BU, Kiray M, et al. The protective effects of tri- metazidine on testicular ischemia and reperfusion injury in rats. Pe- diatr Surg Int 2007;23:1113-8.
  • Elmalı N, Esenkaya I, Karadağ N, et al. Effects of resveratrol on ske- letal muscle in ischemia-reperfusion injury. Ulus Travma Acil Cerra- hi Derg. 2007;13:274-280.
  • Shin T, Kuboki S, Lentsch AB. Roles of nuclear factor-kappaB in postischemic liver. Hepatol Res 2008;38:429-40.
  • Tsung A, Kaizu T, Nakao A, et al. Ethyl pyruvate ameliorates liver ischemia-reperfusion injury by decreasing hepatic necrosis and apoptosis. Transplantation 2005;79:196-204.
  • Hiranuma S, Ito K, Noda Y, et al. Amelioration of hepatic ischemi- a/reperfusion injury in the remnant liver after partial hepatectomy in rats. J Gastroenterol Hepatol 2007;22:2167-72.
  • Schmeding M, Neumann UP, Boas-Knoop S, et al. Erythropoietin reduces ischemia-reperfusion injury in the rat liver. Eur Surg Res 2007;39:189-97.
  • Fabia R, Travis DL, Levy MF, et al. Effect of pentoxifylline on hepa- tic ischemia and reperfusion injury. Surgery 1997;121:520-5.
  • Erdoğan O, Yildiz S, Başaran A, et al. Effect of intraportal verapa- mil infusion on hepatic ischemia-reperfusion injury. Pol J Pharmacol 2001;53:137-41.
  • Ohkawa M, Clemens MG, Chaudry IH. Studies on the mechanism of beneficial effects of ATPMgCl2 following hepatic ischemia. Am J Physiol 1983;244:695-702.
  • Minor T, Isselhard W. Role of the hepatovasculature in free radical mediated reperfusion damage of the liver. Eur Surg Res 1993;25: 287-93.
  • Abdollahi M, Chan TS, Subrahmanyam V, O'Brien PJ. Effects of phosphodiesterase 3,4,5 inhibitors on hepatocyte cAMP levels, glycogenolysis, gluconeogenesis and susceptibility to a mitochon- drial toxin. Mol Cell Biochem 2003;252:205-11.
  • Davila JC, Davis PJ, Acosta D. Changes in glutathione and cellular energy as potential mechanisms of papaverine-induced hepatoto- xicity in vitro. Toxicol Appl Pharmacol 1991;108:28-36.
  • Brown SL, Haas CA, Koehler M, et al. Hepatotoxicity related to in- tracavernous pharmacotherapy with papaverine. Urology 1998; 52:844-7.

Sıçanlarda karaciğer iskemi/reperfüzyon hasarında papaverinin etkisi

Year 2012, Volume: 11 Issue: 1, 2 - 6, 01.04.2012

Abstract

Amaç: Bu çalışmada, fosfodiesteraz inhibitörü ve vazodilatatör bir ajan olan papaverinin hepatik iskemi reperfüzyon hasarına olan etkisini araştırmayı amaçladık. Yöntem: Çalışma, Dokuz Eylül Üniversitesi Deney Hayvanları Laboratuarı'nda yapıldı. Çalışmada yedişerli üç gruba ayrılan toplam 21 adet dişi Wistar albino tipi sıçan kullanıldı. Sham grubu (Grup 1): Sadece batın açılıp kapatıldı. Kontrol grubu (Grup 2): Karaciğer portal triadı mikrovasküler klip ile kliplendi ve iskeminin 30. dakikasında 20 mg/kg serum fizyolojik verildi. Çalışma (Papaverin) grubu (Grup 3): Aynı şekilde portal triad kliplendi ve iskeminin 30. dakikasında 20 mg/kg papaverin uygulandı. Hem çalışma ve hem de kontrol grubunda altmış dakikalık iskemiyi takiben, 120 dakika reperfüzyon uygulandı. Oluşan hasarın histopatolojik değerlendirilmesi Suzuki skorlama sistemine göre yapıldı. Mikroskopik olarak; parankimde; hidropik şişme, granüler dejenerasyon, mikroveziküler vakuolizasyon, makroveziküler vakuolizasyon, fokal nekroz, kordon düzensizliği portal alanda ise; inflamasyon, fibrozis ve sinüzoidlerde ise hiperemi incelendi. Bulgular: Yapılan istatistiksel değerlendirme sonucu, parankimdeki fokal nekroz ve hidropik şişme hariç diğer tüm ölçütlerde çalışma grubunda yer alan sıçanların kontrol grubundakilere nazaran iskemi reperfüzyon hasarını anlamlı derecede azalttığı saptandı. Sonuç: Bu çalışmamızda papaverinin, hepatik iskemi reperfüzyon modelinde hasarı azaltabileceği sonucuna vardık.

References

  • Chiappa AC, Makuuchi M, Zbar AP, et al. Protective effect of methylprednisolone and of intermittent hepatic pedicle clamping during liver vascular inflow occlusion in the rat. Hepatogastroente- rology 2004;51:1439-44.
  • Glanemann M, Strenziok R, Kuntze R, et al. Ischemic preconditio- ning and methylprednisolone both equally reduce hepatic ischemi- a/reperfusion injury. Surgery 2004;135:203-14.
  • Aslan A, Karagüzel G, Çelik M, et al. Pentoxifylline contributes to the hepatic cytoprotective process in rats undergoing hepatic isc- hemia and reperfusion injury. Eur Surg Res 2001;33:285-90.
  • Portakal O, Inal-Erden M. Effects of pentoxifylline and coenzyme Q10 in hepatic ischemia/reperfusion injury. Clin Biochem 1999;32: 461-6.
  • Vardareli E, Sarıçam T, Köken T, et al. The effect of alphatocophe
  • rol and pentoxyfilline on ischemia-reperfusion induced liver injury in rats. Hepatogastroenterology 1998;45:1505-8.
  • Yildirim S, Tok H, Koksal H, et al. Allopurinol plus pentoxifilline in
  • hepatic ischaemia/reperfusion injury. Asian J Surg 2002;25:149- 53.
  • Marteau P, Ballet F, Chazouilleres O, et al. Effect of vasodilators on
  • hepatic microcirculation in cirrhosis: a study in theisolated perfused rat liver. Hepatology 1989;9:820-3.
  • Chazouilleres O, Ballet F, Chretien Y, et al. Protective effect of va
  • sodilators on liver function after long hypothermic preservation: a study in the isolated perfused rat liver. Hepatology 1989;9:824-9.
  • Suzuki S, Nakamura S, Sakaguchi T, et al. Alteration of reticuloen
  • dothelial phagocytic function and tumor necrosis factor-alpha pro- duction after total hepatic ischemia. Transplantation 1997;64:821-7.
  • Boswell-Smith V, Spina D, Page CP. Phosphodiesterase inhibitors. Br J Pharmacol 2006;147 (Suppl 1):S252-7.
  • Krämer SC, Görich J, Oertel F, et al. Non-occlusive mesenteric isc- hemia. Rofo 2003;175:1177-83.
  • Robertazzi RR, Cunningham JN Jr. Intraoperative adjuncts of spinal cord protection. Semin Thorac Cardiovasc Surg 1998;10:29-34.
  • Liu X, Huang Y, Pokreisz P, et al. Nitric oxide inhalation improves microvascular flow and decreases infarction size after myocardial ischemia and reperfusion. J Am Coll Cardiol 2007;50:808-17.
  • Zhang ZG, Zhang QZ, Cheng YN, et al. Antagonistic effects of ul- tra-low-molecular-weight heparin against cerebral ischemia/reper- fusion injury in rats. Pharmacol Res 2007;56:350-5.
  • Bae EH, Lee KS, Lee J, et al. Effects of {alpha}-lipoic acid on ische- mia/reperfusion-induced renal dysfunction in rats. Am J Physiol Re- nal Physiol 2008;294:F272-80.
  • Guneli E, Cavdar Z, Islekel H, et al. N.Erythropoietin protects the in- testine against ischemia/ reperfusion injury in rats. Mol Med 2007;13:509-17.
  • Pekcetin C, Ergur BU, Kiray M, et al. The protective effects of tri- metazidine on testicular ischemia and reperfusion injury in rats. Pe- diatr Surg Int 2007;23:1113-8.
  • Elmalı N, Esenkaya I, Karadağ N, et al. Effects of resveratrol on ske- letal muscle in ischemia-reperfusion injury. Ulus Travma Acil Cerra- hi Derg. 2007;13:274-280.
  • Shin T, Kuboki S, Lentsch AB. Roles of nuclear factor-kappaB in postischemic liver. Hepatol Res 2008;38:429-40.
  • Tsung A, Kaizu T, Nakao A, et al. Ethyl pyruvate ameliorates liver ischemia-reperfusion injury by decreasing hepatic necrosis and apoptosis. Transplantation 2005;79:196-204.
  • Hiranuma S, Ito K, Noda Y, et al. Amelioration of hepatic ischemi- a/reperfusion injury in the remnant liver after partial hepatectomy in rats. J Gastroenterol Hepatol 2007;22:2167-72.
  • Schmeding M, Neumann UP, Boas-Knoop S, et al. Erythropoietin reduces ischemia-reperfusion injury in the rat liver. Eur Surg Res 2007;39:189-97.
  • Fabia R, Travis DL, Levy MF, et al. Effect of pentoxifylline on hepa- tic ischemia and reperfusion injury. Surgery 1997;121:520-5.
  • Erdoğan O, Yildiz S, Başaran A, et al. Effect of intraportal verapa- mil infusion on hepatic ischemia-reperfusion injury. Pol J Pharmacol 2001;53:137-41.
  • Ohkawa M, Clemens MG, Chaudry IH. Studies on the mechanism of beneficial effects of ATPMgCl2 following hepatic ischemia. Am J Physiol 1983;244:695-702.
  • Minor T, Isselhard W. Role of the hepatovasculature in free radical mediated reperfusion damage of the liver. Eur Surg Res 1993;25: 287-93.
  • Abdollahi M, Chan TS, Subrahmanyam V, O'Brien PJ. Effects of phosphodiesterase 3,4,5 inhibitors on hepatocyte cAMP levels, glycogenolysis, gluconeogenesis and susceptibility to a mitochon- drial toxin. Mol Cell Biochem 2003;252:205-11.
  • Davila JC, Davis PJ, Acosta D. Changes in glutathione and cellular energy as potential mechanisms of papaverine-induced hepatoto- xicity in vitro. Toxicol Appl Pharmacol 1991;108:28-36.
  • Brown SL, Haas CA, Koehler M, et al. Hepatotoxicity related to in- tracavernous pharmacotherapy with papaverine. Urology 1998; 52:844-7.
There are 34 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

Nazım Güreş This is me

Cengiz Tavusbay This is me

Osman Yılmaz This is me

Kemal Atahan This is me

Hüsnü Alper Bağrıyanık This is me

Mehmet Hacıyanlı This is me

Özlem Sayin Gür This is me

Hudai Genç This is me

Burhan Yolcuoğlu This is me

Publication Date April 1, 2012
Published in Issue Year 2012 Volume: 11 Issue: 1

Cite

APA Güreş, N., Tavusbay, C., Yılmaz, O., Atahan, K., et al. (2012). Sıçanlarda karaciğer iskemi/reperfüzyon hasarında papaverinin etkisi. Akademik Gastroenteroloji Dergisi, 11(1), 2-6.

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