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Methotrexate-induced renal oxidative stress in rats: the role of a novel antioxidant caffeic acid phenethyl ester

Department of Pediatric Nephrology, School of Medicine, Suleyman Demirel University, 32260 Isparta, Turkey, oktemfaruk{at}hotmail.com

H Ramazan Yilmaz

Department of Medical Biology and Genetics, School of Medicine, Suleyman Demirel University, 32260 Isparta, Turkey

Fehmi Ozguner

Department of Physiology, School of Medicine, Suleyman Demirel University, 32260 Isparta, Turkey

Seref Olgar

Department of Pediatrics, School of Medicine, Suleyman Demirel University, 32260 Isparta, Turkey

Ali Ayata

Department of Pediatrics, School of Medicine, Suleyman Demirel University, 32260 Isparta, Turkey

Ertugrul Uzar

Department of Neurology, School of Medicine, Suleyman Demirel University, 32260 Isparta, Turkey

Efkan Uz

Department of Medical Biology and Genetics, School of Medicine, Suleyman Demirel University, 32260 Isparta, Turkey

The exact mechanisms of methotrexate-induced renal toxicity have not yet been determined. However, several hypotheses have been put forward, including oxidative stress. The aim of this study was to investigate the role of caffeic acid phenethyl ester (Caffeic Ester), a novel antioxidant, on methotrexate-induced renal oxidative stress in rats. Nineteen adult male rats were equally divided into three experimental groups as follows: control group, methotrexate-treated group, and methotrexate-/Caffeic Ester-treated group. A single dose of methotrexate (20 mg/kg) was administered intraperitoneally (ip). Caffeic Ester (10 mmol/kg) was administered ip, once daily for seven days. Malondialdehyde (MDA) levels (an index of lipid peroxidation) were used as a marker of oxidative stress-induced renal injury. Similarly, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were determined to evaluate the changes of antioxidant status in renal tissue. Methotrexate administration to control rats increased MDA levels (PB < 0.0001), but decreased SOD, CAT and GSH-Px activities in renal tissue (PB < 0.0001). Caffeic Ester-/methotrexate treatment caused a significant decrease in MDA levels (PB < 0.001), and caused an increase in SOD, CAT and GSH-Px activities when compared with methotrexate treatment alone (PB < 0.001, < 0.05, < 0.0001, respectively). In conclusion, methotrexate leads to a reduction in antioxidant enzymatic defense capacity and causes lipid peroxidation in renal tissue. Similarly, Caffeic Ester exhibits protective effects on methotrexate-induced renal oxidative impairment in rats.

Key Words: caffeic acid phenethyl ester • kidney • methotrexate • oxidative stress

Toxicology and Industrial Health, Vol. 22, No. 6, 241-247 (2006)
DOI: 10.1191/0748233706th265oa


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