Protective effect of recombinant human erythropoietin against cisplatin-induced oxidative stress and nephrotoxicity in rat kidney.
Cisplatin (Cisp) is one of the most widely used chemotherapeutic agents for the treatment of several human malignancies. The efficacy of Cisp is dose dependent and at higher doses serious kidney injury may occur. 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 study was to explore whether rhEPO administration is protective against Cisp-induced oxidative damage and renal injury. Our results showed that Cisp induced a marked oxidative stress and renal failure. Administration of rhEPO (pre-, co- or postadministration with regard to Cisp) decreased oxidative damage induced by Cisp. Recombinant human EPO reduced malondialdehyde and protein carbonyl levels. Recombinant human EPO also prevented glutathione depletion and ameliorated the increased catalase activity induced by Cisp treatment. Furthermore, rhEPO restored creatinine and blood urea nitrogen levels increased by Cisp. We concluded that rhEPO administration especially in pretreatment condition protected rats against Cisp-induced renal oxidative stress and nephrotoxicity.
Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Monastir, Tunisia.
Karima
K
Rjiba-Touati
Imen Ayed
IA
Boussema
Anis
A
Belarbia
Abdelatif
A
Achour
Hassen
H
Bacha
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000473:pathology; D000818:Animals; D016588:Anticarcinogenic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000008:administration & dosage*; D001806:Blood Urea Nitrogen; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D002945:Cisplatin / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D004921:Erythropoietin / Q000008:administration & dosage*; D005978:Glutathione / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000032:analysis / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D011994:Recombinant Proteins; D004921:Erythropoietin; D008315:Malondialdehyde; D003404:Creatinine; D002374:Catalase; D005978:Glutathione; D002945:Cisplatin