Oxidative stress and protective effect of erythropoietin on methotrexate-induced esophageal damage.
BACKGROUND
An experimental study was conducted to investigate the role of oxidative stress and effects of erythropoietin (EPO) on methotrexate-induced esophageal damage.


METHODS
Twenty-four female Sprague-Dawley rats were equally divided into 3 groups: Sham operation animals (group S) were administered subcutaneous injections of 0.2 mL of 0.9% NaCl; control animals (group MTX) were administered subcutaneous injections of methotrexate (5 mg/kg) and EPO-treated animals (group EPO) were administered subcutaneous injections of methotrexate (5 mg/kg) and EPO (2000 IU/kg) once daily for 4 consecutive days. At the fifth day, the distal 1.5-cm esophageal segments were harvested for biochemical and histologic investigations. Oxidative damage was assessed by measuring the levels of malondialdehyde and nitric oxide, and activities of superoxide dismutase and catalase in homogenized samples of esophageal tissue. Histologic damage to esophageal tissue was scored and total tissue damage scores were calculated.


RESULTS
Malondialdehyde levels in the S and EPO groups were significantly lower than those in the MTX group (P<0.05). Catalase and superoxide dismutase activities, and nitric oxide levels in the S and EPO groups were significantly higher than those in the MTX group (P<0.05). Esophageal tissue damage was significantly less in the EPO group than that in the MTX group (P<0.05).


CONCLUSIONS
Free radicals elevate in methotrexate given rats' esophagus and EPO has significant preventive effects on methotrexate-induced oxidative damage of esophagus in a rat model.
Garipardic
Mesut
M
Departments of Pediatric Hematology and Oncology, Sütcü Imam University, Kahramanmaraş, Turkey. mgaripardic@hotmail.com
Bakan
Vedat
V
Davutoğlu
Mehmet
M
Sayar
Hamide
H
Kurutaş
Ergül Belge
EB
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D004921:Erythropoietin / Q000494:pharmacology*; D004947:Esophagus / Q000187:drug effects* / Q000473:pathology; D005260:Female; D008727:Methotrexate / Q000633:toxicity*; D052016:Mucositis / Q000139:chemically induced; D009569:Nitric Oxide / Q000502:physiology; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley
D000964:Antimetabolites, Antineoplastic; D004921:Erythropoietin; D009569:Nitric Oxide; D008727:Methotrexate