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Effect of thymoquinone on NRF2/NF-kB/MAPK pathway in methotrexate-induced rat testis injury
Emin Kaymak1, Tayfun Ceylan2, Tuğrul Akın3
1Department of Histology and Embryology, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey.
Objectives:
In this study, we aimed to investigate the protective effect of Thymoquinone (THQ) against testicular damage caused by Methotrexate (MTX).
Materials And Methods:
This study consists of 5 groups: Control, Olive oil, THQ, MTX, and MTX+THQ. At the end of the experiment, spermiogram analysis was performed on the rats. In addition, testicular tissues were taken and histopathology, immunohistochemistry, and biochemistry analysis were performed. Biochemical analyses were performed on the serums.
Results:
According to the results obtained, spermiogram values, Johnson's testicular biopsy score, SOD, CAT, GPx, FSH, LH, and testosterone values were statistically significantly decreased in the MTX group compared to the control group. In the MTX+THQ group, spermiogram values, Johnson's testicular biopsy score, SOD, CAT, GPx, FSH, LH, and testosterone values increased statistically significantly compared to the MTX group. NRF2 and HO-1 immunoreactivity were statistically significantly decreased in the MTX group compared to the control group. In the MTX+THQ group, NRF2 and HO-1 immunoreactivity were statistically significantly increased compared to the MTX group. The level of MDA, which is important in lipid damage, and the level of biochemistry results of TNF-α, IL1-β, and IL-6, which are important markers, and the results of p-NF-kB and P38 immunoreactivity were statistically significantly increased in the MTX group compared to the control group. In the MTX+THQ group, these parameters showed a significant decrease compared to the MTX group.
Conclusion:
According to these results, it is thought that THQ will play a protective role against infertility caused by chemotherapy-induced testicular damage.
Insights
Thymoquinone (THQ) protects against Methotrexate (MTX)-induced testicular damage. THQ treatment improved sperm parameters and antioxidant levels, mitigating chemotherapy-related infertility.
Area of Science:
- Reproductive Biology
- Toxicology
- Pharmacology
Background:
- Chemotherapy, particularly Methotrexate (MTX), can cause significant testicular damage and infertility.
- Oxidative stress and inflammation are key mechanisms underlying MTX-induced testicular toxicity.
- Thymoquinone (THQ), a natural compound, has demonstrated antioxidant and anti-inflammatory properties.
Purpose of the Study:
- To investigate the protective effects of Thymoquinone (THQ) against Methotrexate (MTX)-induced testicular damage in a rat model.
- To evaluate the impact of THQ on sperm parameters, testicular histopathology, oxidative stress markers, and relevant protein expression.
Main Methods:
- Rats were divided into five groups: Control, Olive oil, THQ, MTX, and MTX+THQ.
- Spermiogram analysis, histopathology, immunohistochemistry, and biochemical assays (serum and tissue) were performed.
- Key markers assessed included sperm count and motility, Johnson's testicular biopsy score, oxidative stress enzymes (SOD, CAT, GPx), lipid peroxidation (MDA), inflammatory cytokines (TNF-α, IL1-β, IL-6), and signaling proteins (NRF2, HO-1, p-NF-kB, P38).
Main Results:
- MTX treatment significantly reduced sperm parameters, testicular biopsy scores, antioxidant enzyme levels (SOD, CAT, GPx), FSH, LH, and testosterone.
- Conversely, MTX increased MDA levels and inflammatory markers (TNF-α, IL1-β, IL-6), along with p-NF-kB and P38 expression.
- THQ administration in the MTX+THQ group significantly reversed these negative effects, improving all measured parameters and restoring NRF2 and HO-1 expression.
Conclusions:
- Thymoquinone (THQ) exhibits significant protective effects against Methotrexate (MTX)-induced testicular toxicity.
- THQ ameliorates testicular damage by reducing oxidative stress, inflammation, and apoptosis, while enhancing antioxidant defense mechanisms.
- THQ may be a potential therapeutic agent to mitigate chemotherapy-induced infertility.
