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Methotrexate causes oxidative stress in rat kidney tissues
Erdinç Devrim1, Recep Cetin, Bülent Kiliçoğlu
1Department of Biochemistry, Ankara University School of Medicine, Turkey.
Aim:
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.
Conclusion:
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.
Insights
Methotrexate (MTX) treatment increased oxidative stress in rat kidneys, indicated by higher malondialdehyde (MDA) levels. This suggests oxidative damage may contribute to MTX-induced nephrotoxicity.
Area of Science:
- Biochemistry
- Toxicology
- Pharmacology
Background:
- Methotrexate (MTX) is a vital chemotherapeutic agent used for various cancers.
- Nephrotoxicity is a known complication associated with MTX therapy.
- Understanding the mechanisms of MTX-induced kidney damage is crucial for patient safety.
Purpose of the Study:
- To investigate the impact of MTX on the oxidant/antioxidant balance in rat kidney tissues.
- To explore the enzymatic pathways involved in MTX-induced nephrotoxicity.
Main Methods:
- Female Sprague-Dawley rats were administered MTX intravenously weekly for 7 weeks.
- Kidney tissues were analyzed for malondialdehyde (MDA) levels and antioxidant potential (AOP).
- Activities of key enzymes including superoxide dismutase, catalase, and xanthine oxidase were measured.
Main Results:
- A significant increase in MDA levels was observed in the MTX-treated group compared to controls (p<0.05).
- No significant differences were found in antioxidant potential (AOP) values between the groups.
- Enzyme activities related to antioxidant defense and purine metabolism did not show significant changes.
Conclusions:
- MTX treatment induces oxidative stress in rat kidney tissues.
- Elevated oxidative stress is a potential contributing factor to MTX-induced nephrotoxicity.
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