title: Effect of recombinant erythropoietin on ischemia-reperfusion-induced apoptosis in rat liver.
abstract: Ischemia-reperfusion (I/R) cannot be avoided in liver transplantation procedures, and apoptosis is a central mechanism of cell death after liver reperfusion. Protective effect of recombinant erythropoietin (rhEPO) on liver apoptosis has not been clearly investigated. This work investigated intraportal (IP) rhEPO-protective effect in a rat model of hepatic I/R-induced apoptosis and its appropriated time and dose of administration. Eight groups were included (n = 10/group): sham-operated, I/R (45 min ischemia and 2 h reperfusion), preconditioned rhEPO I/R (24 h or 30 min before ischemia), and postconditioned rhEPO I/R (before reperfusion) using two different rhEPO doses (1,000 and 5,000 IU/kg). When compared with the sham-operated group, the I/R group showed significant increase of serum levels of aspartate and alanine aminotransferases (AST, ALT), hepatic caspase-9 activity(894.99 ± 176.90 relative fluorescence units (RFU)/mg/min versus 458.48 ± 82.96 RFU/mg/min), and Fas ligand (FasL) expression, histopathological damages, and significant decrease in the antiapoptotic Bcl-xL/apoptotic Bax ratio(0.38 ± 0.21 versus 3.35 ± 0.77) rhEPO-improved ALT and AST but failed to reduce FasL expression in all groups compared with the I/R group. Thirty minutes and 24 h preconditioning with rhEPO (1,000 IU/kg) increased Bcl-xL/Bax ratio and reduced caspase-9 activity, and the same effect was observed when higher dose was given 24 h before ischemia. Preconditioning was more effective than postconditioning in improving caspase-9 activity, and no dose-dependent effect was observed. In conclusion, single IP rhEPO injection 30 min before ischemia has an advantage over rhEPO postconditioning in improving post-hepatic I/R-induced apoptosis with no additional time- and dose-dependent effects which may provide potentially useful guide in liver transplantation procedures.
authors.affiliation: Department of Physiology, Cairo University Cairo, Cairo, Egypt. heba.shawky.26@gmail.com
authors.forename: Heba M
authors.initials: HM
authors.lastname: Shawky
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Younan
authors.forename: Leila A
authors.initials: LA
authors.lastname: Rashed
authors.forename: Heba
authors.initials: H
authors.lastname: Shoukry
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D053453:Caspase 9 / Q000378:metabolism; D004789:Enzyme Activation; D004921:Erythropoietin / Q000627:therapeutic use*; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D057775:Ischemic Postconditioning; D019194:Ischemic Preconditioning; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic
chemical_list: D051017:Apoptosis Regulatory Proteins; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D011994:Recombinant Proteins; D004921:Erythropoietin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C506435:Casp9 protein, rat; D053453:Caspase 9