title: Protective effect of recombinant human erythropoeitin against cisplatin cytotoxicity and genotoxicity in cultured Vero cells.
abstract: Cisplatin is an effective agent against various solid tumors. Despite its effectiveness, the dose of cisplatin that can be administered is limited by its nephrotoxicity. Therefore, strategies for minimising the toxicity of cisplatin are of a clinical interest. The aim of this study was to investigate the protective effect of recombinant human erythropoietin (rhEPO) against the cytotoxicity and apoptosis induced by cisplatin in cultured Vero cells. Three types of treatments were performed: (i) cells were treated with rhEPO 24 h before exposure to cisplatin (pre-treatment), (ii) cells were treated with rhEPO and cisplatin simultaneously (co-treatment), (iii) cells were treated with rhEPO 24 h after exposure to cisplatin (post-treatment). Our results showed that rhEPO reduced cisplatin-induced cell mortality. Besides, rhEPO administration prevented cisplatin-induced DNA damage. Furthermore, rhEPO decreased the caspase-3 activity and pro-apoptotic factors levels (p53 and Bax) induced by cisplatin. It increased also the expression of the anti-apoptotic factor Bcl2 in Vero cells. Altogether, our results suggest a protective action of rhEPO against cisplatin cytotoxicity and genotoxicity via an anti-apoptotic process. The most protective effect was observed with rhEPO when it was administrated 24 h before cisplatin treatment.
authors.affiliation: Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Monastir University, Monastir, Tunisia.
authors.forename: Karima
authors.initials: K
authors.lastname: Rjiba-Touati
authors.forename: Imen
authors.initials: I
authors.lastname: Ayed-Boussema
authors.forename: Anis
authors.initials: A
authors.lastname: Belarbia
authors.forename: Awatef
authors.initials: A
authors.lastname: Azzebi
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Achour
authors.forename: Hassen
authors.initials: H
authors.lastname: Bacha
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D002945:Cisplatin / Q000633:toxicity*; D020552:Comet Assay; D019610:Cytoprotection / Q000187:drug effects*; D004249:DNA Damage; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology*; D015151:Immunoblotting; D009153:Mutagens / Q000633:toxicity*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014709:Vero Cells; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C554270:EPO protein, human; D009153:Mutagens; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D004921:Erythropoietin; D053148:Caspase 3; D002945:Cisplatin