Methotrexate causes oxidative stress in rat kidney tissues.
OBJECTIVE
Methotrexate (MTX), a folic acid antagonist, is one of the chemotherapeutic agents widely used in the treatment of some types of cancers. Nephrotoxicity is one of the complications of MTX treatment. The aim of this study was to investigate possible effects of MTX treatment on the oxidant/antioxidant status in rat kidney tissues and enzymatic mechanisms leading to nephrotoxicity.


METHODS
For this aim, 10 Sprague-Dawley type female rats of 4 weeks old were used in the study. The animals were divided into two groups randomly. Five of them were used as control, and the others were treated with MTX intravenously (60 mg/m2 of body surface area per week) for 7 weeks. At the end of this period, they were sacrificed, and kidney tissues were removed to be used in the analyses of malondialdehyde (MDA) levels, antioxidant potential (AOP) values, and superoxide dismutase, catalase, glutathione peroxidase, xanthine oxidase, adenosine deaminase, and 5' nucleotidase enzyme activities.


RESULTS
There was significant increase in the MDA level in the MTX group compared with the control group (1.74+/-0.23 nmol/mg vs. 1.04+/-0.30 nmol/mg; p<0.05, respectively). There were however no meaningful differences between enzyme activities and AOP values of the groups.


CONCLUSIONS
It has been suggested that MTX leads to oxidative stress in rat kidney tissues, which might be one of the reasons for MTX-induced nephrotoxicity.
Devrim
Erdinç
E
Department of Biochemistry, Ankara University School of Medicine, Turkey.
Cetin
Recep
R
Kiliçoğlu
Bülent
B
Ergüder
B Imge
BI
Avci
Aslihan
A
Durak
Ilker
I
D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D008727:Methotrexate / Q000009:adverse effects* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011336:Probability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D013482:Superoxide Dismutase / Q000378:metabolism; D046509:Tissue Culture Techniques
D015415:Biomarkers; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D008727:Methotrexate