Protective Strategies Against Methotrexate-Induced Testicular Toxicity
Summary
Methotrexate is a cornerstone in oncology and immunosuppression, but its propensity to disrupt spermatogenesis, deplete antioxidants and trigger apoptosis within the testicular microenvironment represents a major challenge for male reproductive health. Preclinical studies have elucidated that oxidative stress, inflammatory mediators and dysregulated autophagy converge to compromise germ cell viability and steroidogenesis. In response, a spectrum of protective strategies has emerged. Antioxidant phytochemicals and vitamins act by neutralising free radicals and restoring enzymatic defences such as superoxide dismutase and catalase. Modulators of intracellular signalling, including PPAR-γ agonists, have shown potential in attenuating caspase-driven cell death and normalising autophagic flux. Endogenous peptides and natural extracts help to reinforce the blood–testis barrier and mitigate inflammatory cytokine release. Novel approaches such as stem cell therapy and nanocarrier-based delivery systems offer targeted regeneration of damaged seminiferous epithelium. Together, these interventions broaden the arsenal for safeguarding fertility in patients undergoing methotrexate therapy and warrant translation towards clinical evaluation.
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Protective Strategies Against Methotrexate-Induced Testicular Toxicity publication trend
The graph below shows the total number of articles in protective strategies against methotrexate-induced testicular toxicity across all publications each year (not limited to Nature Index journals).
Technical terms
Oxidative stress: Imbalance between reactive oxygen species production and antioxidant defences.
Apoptosis: Programmed cell death characterised by caspase activation and DNA fragmentation.
Autophagy: Cellular process of degrading and recycling damaged organelles and proteins.
Peroxisome proliferator-activated receptor-γ (PPAR-γ): Nuclear receptor involved in lipid metabolism and anti-inflammatory signalling.
Malondialdehyde (MDA): Biomarker of lipid peroxidation and oxidative membrane damage.
References
- Beneficial role of naringin against methotrexate-induced injury to rat testes: biochemical and ultrastructural analyses. Redox Report (2022).
- Mechanistic aspects of ameliorative effects of Eicosapentanoic acid ethyl ester on methotrexate-evoked testiculopathy in rats. Naunyn-Schmiedeberg's Archives of Pharmacology (2023).
- Effect of Betaine on Apoptosis and Oxidative Stress in Methotrexate‐Induced Testicular Damage in Mice. Andrologia (2024).
- Therapeutic Effect of Stem Cells on Male Infertility in a Rat Model: Histological, Molecular, Biochemical, and Functional Study. Stem Cells International (2021).
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