title: Methotrexate-induced renal oxidative stress in rats: the role of a novel antioxidant caffeic acid phenethyl ester.
abstract: 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 micromol/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 (P<0.0001), but decreased SOD, CAT and GSH-Px activities in renal tissue (P<0.0001). Caffeic Ester+ methotrexate treatment caused a significant decrease in MDA levels (P<0.001), and caused an increase in SOD, CAT and GSH-Px activities when compared with methotrexate treatment alone (P<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.
authors.affiliation: Department of Pediatric Nephrology, School of Medicine, Suleyman Demirel University, 32260 Isparta, Turkey. oktemfaruk@hotmail.com
authors.forename: Faruk
authors.initials: F
authors.lastname: Oktem
authors.forename: H Ramazan
authors.initials: HR
authors.lastname: Yilmaz
authors.forename: Fehmi
authors.initials: F
authors.lastname: Ozguner
authors.forename: Seref
authors.initials: S
authors.lastname: Olgar
authors.forename: Ali
authors.initials: A
authors.lastname: Ayata
authors.forename: Ertugrul
authors.initials: E
authors.lastname: Uzare
authors.forename: Efkan
authors.initials: E
authors.lastname: Uz
mesh_terms: D000818:Animals; D002109:Caffeic Acids / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008727:Methotrexate; D018384:Oxidative Stress / Q000187:drug effects*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D002109:Caffeic Acids; D016166:Free Radical Scavengers; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; D008727:Methotrexate