Effect of recombinant human erythropoietin on mitomycin C-induced oxidative stress and genotoxicity in rat kidney and heart tissues.
Mitomycin C (MMC) is an antineoplastic agent used for the treatment of several human malignancies. Nevertheless, the prolonged use of the drug may result in a serious heart and kidney injuries. Recombinant human erythropoietin (rhEPO) has recently been shown to exert an important cytoprotective effect in experimental brain injury and ischemic acute renal failure. The aim of the present work is to investigate the cardioprotective and renoprotective effects of rhEPO against MMC-induced oxidative damage and genotoxicity. Our results showed that MMC induced oxidative stress and DNA damage. rhEPO administration in any treatment conditions decreased oxidative damage induced by MMC. It reduced malondialdehyde and protein carbonyl levels. rhEPO ameliorated reduced glutathione plus oxidized glutathione modulation and the increased catalase activity after MMC treatment. Furthermore, rhEPO restored DNA damage caused by MMC. We concluded that rhEPO administration especially in pretreatment condition protected rats against MMC-induced heart and renal oxidative stress and genotoxicity.
Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Monastir, Tunisia.
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Rjiba-Touati
Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Monastir, Tunisia.
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Ayed-Boussema
Department of Nephrology, Dialysis and Transplant, University Hospital of Sahloul, Sousse, Tunisia.
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Guedri
Department of Nephrology, Dialysis and Transplant, University Hospital of Sahloul, Sousse, Tunisia.
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Achour
Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Monastir, Tunisia hassen.bacha@fmdm.rnu.tn.
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Bacha
Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Monastir, Tunisia.
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Abid-Essefi
D000477:Alkylating Agents / Q000009:adverse effects; D000818:Animals; D002374:Catalase / Q000378:metabolism; D020552:Comet Assay; D004249:DNA Damage; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000494:pharmacology*; D005978:Glutathione; D006321:Heart / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D016685:Mitomycin / Q000009:adverse effects*; D009152:Mutagenicity Tests; D009206:Myocardium; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation; D051381:Rats
D000477:Alkylating Agents; D004921:Erythropoietin; D016685:Mitomycin; D002374:Catalase; D005978:Glutathione
antigenotoxic effect; antioxidant effect; mitomycin C; rhEPO