title: Protective effect of erythropoietin against cisplatin-induced nephrotoxicity in rats: antigenotoxic and antiapoptotic effect.
abstract: Cisplatin (Cisp) is an active cytotoxic agent that was found efficient in the treatment of various types of solid tumors. Its nephrotoxic effect has been very well documented in clinical oncology. Erythropoietin (EPO), a renal cytokine-regulating hematopoiesis, has recently been shown to exert important cytoprotective effects in many experimental injuries. The aim of this study was to explore whether EPO would protect against Cisp-induced apoptosis in rat kidney. Adult Wistar rats were treated with saline solution as the control group, Cisp alone, EPO alone, or EPO with Cisp in different treatments: 1) EPO and Cisp simultaneously administrated to animals as a cotreatment; 2) EPO administered 24 hours before Cisp as a pretreatment; and 3) EPO administered 5 days after Cisp injection as a post-treatment. Our results have shown that Cisp induced renal failure, characterized with a significant increase in serum creatinine and blood urea nitrogen (BUN) concentrations. Cisp promoted kidney DNA fragmentation and apoptotic cell death. Apoptosis was revealed by an enhancement of proapoptotic protein (e.g., p53 and Bax) levels, decrease in antiapoptotic proteins (e.g., Bcl2 and Hsp27), and increase in caspase-3 activity. Treatments with EPO restored creatinine and BUN levels and inhibited Cisp-induced DNA damage in the kidney. Apoptosis was also reduced by the upregulation of antiapoptotic protein expressions, downregulation of proapoptotic protein levels, and reduction of caspase-3 activity.
authors.affiliation: Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Monastir, Tunisia.
authors.forename: Karima
authors.initials: K
authors.lastname: Rjiba-Touati
authors.forename: Imen
authors.initials: I
authors.lastname: Ayed-Boussema
authors.forename: Chayma
authors.initials: C
authors.lastname: Bouaziz
authors.forename: Anis
authors.initials: A
authors.lastname: Belarbia
authors.forename: Awatef
authors.initials: A
authors.lastname: Azzabi
authors.forename: Abdelatif
authors.initials: A
authors.lastname: Achour
authors.forename: Wafa
authors.initials: W
authors.lastname: Hassen
authors.forename: Hassen
authors.initials: H
authors.lastname: Bacha
mesh_terms: D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D004249:DNA Damage / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D009153:Mutagens / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000139:chemically induced / Q000517:prevention & control*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016587:Antimutagenic Agents; D000970:Antineoplastic Agents; D009153:Mutagens; D004921:Erythropoietin; D003404:Creatinine; D002945:Cisplatin