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The protective effect of Ozone on the mice testicular damage induced by methotrexate
Layasadat Khorsandi1,2, Negar Varaa3, Reza Dadfar4
1Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Objective:
Methotrexate (MTX) is widely administered for the treatment of various cancers. However, MTX induces male reproductive toxicity. In the current study, the effect of ozone therapy (OT) on reducing the toxic effects of MTX in the mouse testicles has been investigated.
Methods:
Twenty-four mice were divided into four groups: control, OT (4 mg/kg ozone), MTX (20 mg/kg), and MTX + OT. Testosterone levels, histological changes, and oxidative stress biomarkers were assessed to evaluate the protective effects of OT.
Results:
The results demonstrated that MTX disrupted germinal epithelium, reduced serum testosterone levels, and enhanced oxidative stress in testicular tissue. However, treatment with OT attenuated these adverse effects. OT effectively restored the levels of antioxidant enzymes, such as catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD). OT reduced lipid peroxidation, as indicated by decreased malondialdehyde (MDA) levels. OT preserved normal spermatogenesis, improved morphometric parameters, and reduced histological changes by MTX. Moreover, OT effectively restored testosterone levels.
Conclusions:
OT protects against MTX-induced testicular damage by suppressing oxidative stress.
Insights
Ozone therapy (OT) mitigates testicular toxicity caused by methotrexate (MTX) chemotherapy. OT treatment effectively restored testosterone levels and protected against MTX-induced oxidative stress and damage in male mice.
Area of Science:
- Reproductive Toxicology
- Oxidative Stress Research
- Cancer Therapy Adjuncts
Background:
- Methotrexate (MTX) is a cornerstone chemotherapy agent with known male reproductive toxicity.
- MTX-induced testicular damage involves disruption of germinal epithelium and hormonal imbalance.
- Oxidative stress is a key mechanism underlying MTX-induced male infertility.
Purpose of the Study:
- To investigate the protective effects of ozone therapy (OT) against MTX-induced testicular toxicity in a mouse model.
- To evaluate the impact of OT on hormonal levels, histological integrity, and oxidative stress markers in MTX-treated mice.
Main Methods:
- Male mice were divided into four groups: control, OT, MTX, and MTX + OT.
- Animals received specific dosages of ozone (4 mg/kg) and MTX (20 mg/kg).
- Assessment included serum testosterone levels, testicular histology, and oxidative stress biomarkers (CAT, GSH, SOD, MDA).
Main Results:
- MTX treatment significantly disrupted testicular germinal epithelium and reduced testosterone levels.
- MTX administration led to increased oxidative stress, evidenced by elevated MDA and reduced antioxidant enzyme activity.
- OT treatment counteracted MTX effects, restoring antioxidant enzyme levels, decreasing lipid peroxidation, preserving spermatogenesis, and normalizing testosterone levels.
Conclusions:
- Ozone therapy demonstrates significant protective effects against methotrexate-induced testicular damage.
- OT mitigates MTX toxicity by suppressing oxidative stress and restoring testicular function.
- OT represents a potential therapeutic strategy to ameliorate chemotherapy-induced male reproductive toxicity.
