Effect of recombinant erythropoietin on ischemia-reperfusion-induced apoptosis in rat liver.

作者: Heba M. Shawky , Sandra M. Younan , Leila A. Rashed , Heba Shoukry

DOI: 10.1007/S13105-011-0114-2

关键词: Programmed cell deathLiver transplantationRelative fluorescence unitsFas ligandRat liverMedicineIschemiaRecombinant erythropoietinImmunologyPharmacologyApoptosis

摘要: Ischemia–reperfusion (I/R) cannot be avoided in liver transplantation procedures, and apoptosis is a central mechanism of cell death after reperfusion. Protective effect recombinant erythropoietin (rhEPO) on has not been clearly investigated. This work investigated intraportal (IP) rhEPO-protective rat model hepatic I/R-induced its appropriated time dose administration. Eight groups were included (n = 10/group): sham-operated, I/R (45 min ischemia 2 h reperfusion), preconditioned rhEPO (24 or 30 before ischemia), postconditioned (before reperfusion) using two different doses (1,000 5,000 IU/kg). When compared with the sham-operated group, group showed significant increase serum levels aspartate alanine aminotransferases (AST, ALT), caspase-9 activity(894.99 ± 176.90 relative fluorescence units (RFU)/mg/min versus 458.48 82.96 RFU/mg/min), Fas ligand (FasL) expression, histopathological damages, decrease antiapoptotic Bcl-xL/apoptotic Bax ratio(0.38 0.21 3.35 0.77) rhEPO-improved ALT AST but failed to reduce FasL expression all group. Thirty minutes 24 preconditioning IU/kg) increased Bcl-xL/Bax ratio reduced activity, same was observed when higher given ischemia. Preconditioning more effective than postconditioning improving no dose-dependent observed. In conclusion, single IP injection an advantage over post-hepatic additional time- effects which may provide potentially useful guide procedures.

参考文章(28)
Guido Kroemer, John C. Reed, Mitochondrial control of cell death Nature Medicine. ,vol. 6, pp. 513- 519 ,(2000) , 10.1038/74994
Erik Lipšic, Regien G. Schoemaker, Peter van der Meer, Adriaan A. Voors, Dirk J. van Veldhuisen, Wiek H. van Gilst, Protective Effects of Erythropoietin in Cardiac Ischemia Journal of the American College of Cardiology. ,vol. 48, pp. 2161- 2167 ,(2006) , 10.1016/J.JACC.2006.08.031
S. W. Fesik, STRUCTURAL BIOLOGY: Controlling the Caspases Science. ,vol. 294, pp. 1477- 1478 ,(2001) , 10.1126/SCIENCE.1062236
Sezgin Yilmaz, Ersin Ates, Cigdem Tokyol, Turan Pehlivan, Serdar Erkasap, Tulay Koken, The protective effect of erythropoietin on ischaemia/reperfusion injury of liver. Hpb. ,vol. 6, pp. 169- 173 ,(2004) , 10.1080/13651820410026077
Friedrich Duenschede, Kirsten Erbes, Achim Kircher, Stefanie Westermann, Arno Schad, Nina Riegler, Patrick Ewald, Philipp Dutkowski, Alexandra K. Kiemer, Oliver Kempski, Theodor Junginger, Protection from hepatic ischemia/reperfusion injury and improvement of liver regeneration by alpha-lipoic acid. Shock. ,vol. 27, pp. 644- 651 ,(2007) , 10.1097/01.SHK.0000248582.25647.EE
Pronobesh Chattopadhyay, Navneet Verma, Anurag Verma, Tirath Kamboj, Nazam Ali Khan, Arun Kumar Wahi, L-Arginine Protects from Pringle Manoeuvere of Ischemia-Reperfusion Induced Liver Injury Biological & Pharmaceutical Bulletin. ,vol. 31, pp. 890- 892 ,(2008) , 10.1248/BPB.31.890
Thierry Hauet, Denis Mothes, Jean-Michel Goujon, Jean Claude Caritez, Michel Carretier, Laurence le Moyec, Michel Eugene, Jean-Paul Tillement, Trimetazidine prevents renal injury in the isolated perfused pig kidney exposed to prolonged cold ischemia. Transplantation. ,vol. 64, pp. 1082- 1086 ,(1997) , 10.1097/00007890-199710150-00025
Lindsey A. Allan, Nick Morrice, Suzanne Brady, Gareth Magee, Shalini Pathak, Paul R. Clarke, Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK Nature Cell Biology. ,vol. 5, pp. 647- 654 ,(2003) , 10.1038/NCB1005
Franklin Greif, Ziv Ben-Ari, Rasim Taya, Orit Pappo, Efrat Kurtzwald, Yelena Cheporko, Amiram Ravid, Edith Hochhauser, Dual effect of erythropoietin on liver protection and regeneration after subtotal hepatectomy in rats Liver Transplantation. ,vol. 16, pp. 631- 638 ,(2010) , 10.1002/LT.22046
Andreas Hartkorn, Florian Hoffmann, Hussam Ajamieh, Susanne Vogel, Jörg Heilmann, Alexander L. Gerbes, Angelika M. Vollmar, Stefan Zahler, Antioxidant effects of xanthohumol and functional impact on hepatic ischemia-reperfusion injury. Journal of Natural Products. ,vol. 72, pp. 1741- 1747 ,(2009) , 10.1021/NP900230P