Protective effects of apocynin on damaged testes of rats exposed to methotrexate
Kübra Kavram Sarihan1, Melda Yardimoğlu Yilmaz1, Fatma Ceyla Eraldemir2
1Department of Histology and Embryology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey
Background/Aim:
Methotrexate (MTX), widely used as a drug in cancer, has many adverse effects on tissues. Apocynin (APO) is a NADPH oxidase inhibitor and is known with many antioxidant properties. In this study, we aimed to evaluate the adverse effects of MTX on testicular tissue and the protective effects of APO at two different doses (20 mg/kg and 50 mg/kg) on MTX-induced testicular damage.
Materials And Methods:
Fifty adult male Wistar albino rats (8 weeks old and weighing 200–250 g) were divided into five groups of 10 rats each: 1. saline control, 2. dimethyl sulfoxide (DMSO) control, 3. MTX, 4. APO-20 + MTX, and 5. APO-50 + MTX. All injections were performed intraperitoneally. At the end of day 28, all rats were sacrificed under anesthesia. The testes were evaluated histologically and the blood samples were analyzed biochemically.
Results:
According to histological and biochemical analyses, there was no significant difference between the DMSO and control groups. In terms of the histological findings, MTX group was significantly the worst affected group compared to the others, and in this group, apoptotic cell number (P = 0.011) was significantly increased in comparison with the control group. Except MTX, there was no significant difference in apoptotic cell number of the other groups compared to the control group. In the MTX group, malondialdehyde (MDA, P = 0.017) and myeloperoxidase (MPO, P < 0.001) levels were significantly increased in tissue and in blood (MDA P < 0.001, MPO P < 0.001), while tissue glutathione (GSH, P < 0.05) and serum testosterone levels (P < 0.01) were decreased compared with the control group. APO + MTX treatment groups exhibited better testis morphology, and apoptotic cells were also significantly decreased compared to MTX group (P < 0.001).
Conclusion:
Our results suggest that MTX induced defects on testis via oxidative stress and APO reversed the effects of MTX with its antioxidant properties.
Insights
Methotrexate causes testicular damage through oxidative stress, but apocynin, an antioxidant, effectively protects against these harmful effects. Apocynin treatment reversed methotrexate-induced testicular damage in rats.
Area of Science:
- Toxicology
- Pharmacology
- Reproductive Biology
Background:
- Methotrexate (MTX) is a widely used chemotherapy drug with known adverse effects on various tissues.
- Apocynin (APO) is a NADPH oxidase inhibitor with significant antioxidant properties.
Purpose of the Study:
- To investigate the adverse effects of MTX on testicular tissue.
- To evaluate the protective potential of apocynin (APO) against MTX-induced testicular damage.
Main Methods:
- Adult male Wistar albino rats were divided into five groups: control, DMSO control, MTX, APO-20 + MTX, and APO-50 + MTX.
- Testes were analyzed histologically, and blood samples were assessed biochemically after 28 days of treatment.
- Apocynin was administered at two doses: 20 mg/kg and 50 mg/kg.
Main Results:
- MTX significantly increased apoptotic cells, malondialdehyde (MDA), and myeloperoxidase (MPO) levels, while decreasing glutathione (GSH) and testosterone levels.
- MTX-induced testicular damage was evident histologically.
- Apocynin treatment at both doses significantly reduced apoptotic cells and improved testicular morphology compared to the MTX group.
Conclusions:
- MTX induces testicular damage primarily through oxidative stress mechanisms.
- Apocynin demonstrates significant protective effects against MTX-induced testicular toxicity due to its antioxidant properties.
