title: Antioxidant and antigenotoxic role of recombinant human erythropoeitin against alkylating agents: cisplatin and mitomycin C in cultured Vero cells.
abstract: Cisplatin (CDDP) and mitomycin C (MMC), two alkylating agents used against various solid tumours, are a common source of acute kidney injury. Thus, strategies for minimizing CDDP and MMC toxicity are of a clinical interest. In this study, we aimed to investigate the protective role of recombinant human erythropoietin (rhEPO) against oxidative stress and genotoxicity induced by CDDP and MMC in cultured Vero cells. Three types of treatments were performed: (i) cells were treated with rhEPO 24 h before exposure to CDDP/MMC (pre-treatment), (ii) cells were treated with rhEPO and CDDP/MMC simultaneously (co-treatment), (iii) cells were treated with rhEPO 24 h after exposure to CDDP/MMC (post-treatment). Our results showed that rhEPO decreased the reactive oxygen species levels, the malondialdehyde levels and ameliorated glutathione (reduced and oxidized glutathione) modulation induced by CDDP and MMC in cultured Vero cells. Furthermore, rhEPO administration prevented alkylating agents-induced DNA damage accessed by comet test. Altogether, our results suggested a protective role of rhEPO, against CDDP- and MMC-induced oxidative stress and genotoxicity, especially in pre-treatment condition.
authors: Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Monastir University, Tunisia.
authors: Karima
authors: K
authors: Rjiba-Touati
authors: Imen
authors: I
authors: Ayed-Boussema
authors: Nidhal
authors: N
authors: Soualeh
authors: Abdellatif
authors: A
authors: Achour
authors: Hassen
authors: H
authors: Bacha
authors: Salwa
authors: S
authors: Abid
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D000477:Alkylating Agents / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D002945:Cisplatin / Q000009:adverse effects* / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects* / Q000502:physiology; D004921:Erythropoietin / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D016685:Mitomycin / Q000009:adverse effects* / Q000494:pharmacology; D023421:Models, Animal; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014709:Vero Cells
chemical_list: D000477:Alkylating Agents; D000975:Antioxidants; C554270:EPO protein, human; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D004921:Erythropoietin; D008315:Malondialdehyde; D016685:Mitomycin; D005978:Glutathione; D002945:Cisplatin
keywords: antioxidant property; antigenotoxic property; cisplatin; mitomycin C; recombinant human erythropoietin (rhEPO)