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Therapeutic potential of diosgenin against methotrexate-induced testicular damage in the rat
Fatemeh Taleahmad1, Mohsen Khalili1, Narges Haddadzadeh-Niri1
1Department of Physiology, School of Medicine, Shahed University, Tehran, Iran.
Abstract:
This study evaluated diosgenin effects on methotrexate-induced testicular injury in the rats. A single dose of methotrexate (MTX) (20 mg/kg, i.p) was administered, followed by two weeks of diosgenin treatment via gavage starting one day before methotrexate injection. Testicular damage was evaluated through histological examination of seminiferous tubules, as well as analysis of serum testosterone level, oxidative stress and inflammation biomarkers, and antioxidant levels. The results of this study showed that in the MTX-exposed group, oxidative stress indices of malondialdehyde (MDA), reactive oxygen species (ROS), nitrite and indices of inflammation consisting of tumor necrosis factor α (TNFα), and interleukin 6 (IL-6) have a significant increase compared to the control group. Additionally, reductions were observed in antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). In addition, testosterone level decreased and signs of testicular damage were observed in the MTX group. Conversely, in the group treated with diosgenin alongside MTX at a dosage of 50 mg/kg, there was a significant decrease in oxidative stress markers (MDA, ROS, nitrite) and inflammatory markers (TNFα and IL-6). Moreover, there was a significant increase in the levels of antioxidant enzymes (SOD, CAT, and GSH). Diosgenin appears to have the potential to protect testicular tissue from damage caused by the toxic effects of MTX through the reduction of oxidative stress and inflammation.
Insights
Diosgenin protects against methotrexate-induced testicular injury by reducing oxidative stress and inflammation. This study in rats demonstrates diosgenin
Area of Science:
- Reproductive toxicology
- Pharmacology
Background:
- Methotrexate (MTX) is a chemotherapy agent with known testicular toxicity.
- Oxidative stress and inflammation are key mechanisms in MTX-induced testicular damage.
Purpose of the Study:
- To evaluate the protective effects of diosgenin against MTX-induced testicular injury in rats.
- To investigate the impact of diosgenin on oxidative stress, inflammation, and antioxidant levels in MTX-treated rats.
Main Methods:
- Rats were administered a single dose of MTX (20 mg/kg).
- Diosgenin (50 mg/kg) was administered via gavage for two weeks, starting before MTX injection.
- Evaluations included histological examination, serum testosterone levels, oxidative stress markers (MDA, ROS, nitrite), inflammatory markers (TNFα, IL-6), and antioxidant enzymes (SOD, CAT, GSH).
Main Results:
- MTX treatment significantly increased oxidative stress and inflammation markers while decreasing antioxidant enzyme levels and serum testosterone.
- Diosgenin treatment significantly reduced oxidative stress and inflammation markers (MDA, ROS, nitrite, TNFα, IL-6).
- Diosgenin treatment significantly increased antioxidant enzyme levels (SOD, CAT, GSH) and improved histological findings.
Conclusions:
- Diosgenin exhibits significant protective effects against MTX-induced testicular toxicity in rats.
- Diosgenin mitigates testicular damage by reducing oxidative stress and inflammation.
- Diosgenin holds potential as a therapeutic agent to counteract MTX-related reproductive side effects.

