The activities of purine-catabolizing enzymes and the level of nitric oxide in rat kidneys subjected to methotrexate: protective effect of caffeic acid phenethyl ester.
The aim of this experimental study was to investigate the possible role of nitric oxide (NO) levels, and activities of adenosine deaminase (ADA) and xanthine oxidase (XO) in the pathogenesis of methotrexate-induced nephrotoxicity, and was the effect of caffeic acid phenethyl ester (CAPE), the potent free radical scavenger, in decreasing the toxicity. A total of 19 adult male rats were divided into three experimental groups, as follows: control group, MTX-treated group, and MTX+CAPE treated group. MTX were administered intraperitoneally (i.p.) with 20 mg/kg for single dose. CAPE was administered i.p. with a dose of 10 micromol//kg once daily for 7 days. The injection of MTX induced a significant increase in the activities of ADA and XO, and NO levels in renal tissue of rats (p < 0.0001). Co-treatment with CAPE caused a significantly decrease activities of ADA and XO, and the levels of NO in renal tissue (p < 0.0001). The results of this study revealed that NO, XO and ADA may play an important role in the pathogenesis of MTX-induced oxidative renal damage. CAPE may have protective potential in this process and it will become a promising drug in the prevention of this undesired side effect of MTX.
Uz
Efkan
E
Department of Medical Biology and Genetics, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey. efkanuz@yahoo.com
Oktem
Faruk
F
Yilmaz
H Ramazan
HR
Uzar
Ertuğrul
E
Ozgüner
Fehmi
F
D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity; D002109:Caffeic Acids / Q000494:pharmacology*; D005493:Folic Acid Antagonists / Q000633:toxicity; D016166:Free Radical Scavengers / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008727:Methotrexate / Q000037:antagonists & inhibitors / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D011687:Purines / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014969:Xanthine Oxidase / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D002109:Caffeic Acids; D005493:Folic Acid Antagonists; D016166:Free Radical Scavengers; D011687:Purines; D009569:Nitric Oxide; D014969:Xanthine Oxidase; D000243:Adenosine Deaminase; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; D008727:Methotrexate