Novel evidence suggesting an anti-oxidant property for erythropoietin on vancomycin-induced nephrotoxicity in a rat model.
1. The aim of the present study was to investigate the role of oxidative stress in renal injury and to determine whether erythropoietin (EPO) acts as an anti-oxidant in vancomycin (VCM)-induced renal impairment. 2. Twenty-four rats were divided into three groups as follows: (i) control (Group 1); (ii) VCM treated (Group 2); and (iii) VCM + EPO treated (Group 3). Vancomycin (200 mg/kg, i.p.) was administered to Groups 2 and 3 for 7 days. Erythropoietin (150 IU/kg, i.p.) treatment was started 24 h before VCM and lasted for 7 days. On Day 8, renal tissues were excised and blood samples were collected. Serum creatinine and blood urea nitrogen were measured, along with renal malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activity and tissue VCM levels. The kidneys were examined for any histopathological changes. 3. Renal MDA levels were found to be increased, whereas SOD and CAT activity was decreased, in the VCM-treated group compared with the control group. There was a marked decrease in MDA levels and an increase in SOD activity, but not CAT activity, after VCM + EPO treatment. Marked histopathological alterations, including interstitial oedema, tubular dilatation, tubular epithelial cell desquamation and vacuolization, were observed in VCM-treated rats. Histopathological changes were significantly improved after EPO administration. 4. In conclusion, the present data suggest that oxidative stress plays an important role in VCM-induced nephrotoxicity. Erythropoietin seems to act as an anti-oxidant, diminishing the toxic oxidative effects of VCM on renal tissues.
Cetin
Hasan
H
Department of Pediatrics, Medical Faculty, Suleyman Demirel University, Isparta, Turkey. hasanctn32@yahoo.com
Olgar
Seref
S
Oktem
Faruk
F
Ciris
Metin
M
Uz
Efkan
E
Aslan
Cağatay
C
Ozguner
Fehmi
F
D000818:Animals; D000900:Anti-Bacterial Agents; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001806:Blood Urea Nitrogen; D002374:Catalase / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D013482:Superoxide Dismutase / Q000378:metabolism; D014640:Vancomycin
D000900:Anti-Bacterial Agents; D000975:Antioxidants; D011994:Recombinant Proteins; D004921:Erythropoietin; D008315:Malondialdehyde; D000068817:Epoetin Alfa; D014640:Vancomycin; D003404:Creatinine; D002374:Catalase; D013482:Superoxide Dismutase