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Protective effect of erythropoietin against cisplatin-induced nephrotoxicity in rats: antigenotoxic and antiapoptotic effect.
Drug Chem Toxicol. 2012 Jan; 35(1):89-95.DC

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+Show Affiliations

Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Monastir, Tunisia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21834728

Citation

Rjiba-Touati, Karima, et al. "Protective Effect of Erythropoietin Against Cisplatin-induced Nephrotoxicity in Rats: Antigenotoxic and Antiapoptotic Effect." Drug and Chemical Toxicology, vol. 35, no. 1, 2012, pp. 89-95.
Rjiba-Touati K, Ayed-Boussema I, Bouaziz C, et al. Protective effect of erythropoietin against cisplatin-induced nephrotoxicity in rats: antigenotoxic and antiapoptotic effect. Drug Chem Toxicol. 2012;35(1):89-95.
Rjiba-Touati, K., Ayed-Boussema, I., Bouaziz, C., Belarbia, A., Azzabi, A., Achour, A., Hassen, W., & Bacha, H. (2012). Protective effect of erythropoietin against cisplatin-induced nephrotoxicity in rats: antigenotoxic and antiapoptotic effect. Drug and Chemical Toxicology, 35(1), 89-95. https://doi.org/10.3109/01480545.2011.589440
Rjiba-Touati K, et al. Protective Effect of Erythropoietin Against Cisplatin-induced Nephrotoxicity in Rats: Antigenotoxic and Antiapoptotic Effect. Drug Chem Toxicol. 2012;35(1):89-95. PubMed PMID: 21834728.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective effect of erythropoietin against cisplatin-induced nephrotoxicity in rats: antigenotoxic and antiapoptotic effect. AU - Rjiba-Touati,Karima, AU - Ayed-Boussema,Imen, AU - Bouaziz,Chayma, AU - Belarbia,Anis, AU - Azzabi,Awatef, AU - Achour,Abdelatif, AU - Hassen,Wafa, AU - Bacha,Hassen, Y1 - 2011/08/12/ PY - 2011/8/13/entrez PY - 2011/8/13/pubmed PY - 2012/4/6/medline SP - 89 EP - 95 JF - Drug and chemical toxicology JO - Drug Chem Toxicol VL - 35 IS - 1 N2 - 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. SN - 1525-6014 UR - https://www.unboundmedicine.com/medline/citation/21834728/Protective_effect_of_erythropoietin_against_cisplatin_induced_nephrotoxicity_in_rats:_antigenotoxic_and_antiapoptotic_effect_ L2 - https://www.tandfonline.com/doi/full/10.3109/01480545.2011.589440 DB - PRIME DP - Unbound Medicine ER -