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Lemon Balm Attenuates Methotrexate-Induced Testicular Damage Through Modulation of Oxidative Stress and p-p38 MAPK
Hanaa S S Gazwi1,2, Esraa M Megahed1, Anwar Ahmed3
1Departments of Agricultural Chemistry, Faculty of Agriculture, Minia University, El-Minia, Egypt.
Abstract:
This study investigated the protective effects of Lemon balm (Melissa officinalis) extract against methotrexate (MTX)-induced testicular toxicity in male Wistar rats. Thirty-two rats were divided into four groups: control, Lemon balm, MTX, and MTX + Lemon balm. MTX was administered intraperitoneally at 20 mg/kg on day 23, while Lemon balm was given orally at 100 mg/kg daily. The MTX-treated group showed significant reductions in body and testicular weight, sperm quality, and reproductive hormone levels [testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH)]. There was also a marked increase in oxidative stress markers [malondialdehyde (MDA), nitric oxide (NO)] and inflammation markers [tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-1β, 8-hydroxy-2'-deoxyguanosine (8-OHdG)]. Immunohistochemical analysis revealed strong p-p38 mitogen-activated protein kinase (MAPK) expression in testicular tissues of the MTX group. Co-treatment with Lemon balm significantly improved sperm parameters and hormone levels while reducing oxidative and inflammatory responses, including marked downregulation of p-p38 MAPK expression. These findings suggest that Lemon balm extract may alleviate MTX-induced testicular toxicity through antioxidant, anti-inflammatory, and p-p38 MAPK pathway modulation.
Insights
Lemon balm extract protects against methotrexate-induced testicular toxicity in rats. It improves sperm quality and hormone levels by reducing oxidative stress, inflammation, and p-p38 MAPK pathway activation.
Area of Science:
- Pharmacology and Toxicology
- Reproductive Biology
- Natural Product Research
Background:
- Methotrexate (MTX) is a chemotherapy agent known to cause testicular toxicity.
- Oxidative stress, inflammation, and hormonal imbalances are key mechanisms in MTX-induced testicular damage.
- Natural compounds are being explored for their protective effects against drug-induced toxicities.
Purpose of the Study:
- To evaluate the protective potential of Lemon balm (Melissa officinalis) extract against MTX-induced testicular toxicity in male Wistar rats.
- To investigate the underlying mechanisms, including antioxidant, anti-inflammatory, and signaling pathway modulation.
Main Methods:
- Thirty-two male Wistar rats were divided into control, Lemon balm extract, MTX, and MTX + Lemon balm extract groups.
- MTX was administered intraperitoneally, and Lemon balm extract was given orally daily.
- Assessment included body/testicular weight, sperm quality, reproductive hormone levels, oxidative/inflammatory markers, and immunohistochemical analysis of p-p38 MAPK.
Main Results:
- MTX treatment significantly reduced body and testicular weight, sperm quality, and reproductive hormone levels (testosterone, LH, FSH).
- MTX increased oxidative stress (MDA, NO) and inflammation markers (TNF-α, IL-6, IL-1β, 8-OHdG) and upregulated testicular p-p38 MAPK expression.
- Lemon balm co-treatment significantly ameliorated these adverse effects, improving sperm parameters and hormone levels while reducing oxidative/inflammatory markers and p-p38 MAPK expression.
Conclusions:
- Lemon balm extract demonstrates significant protective effects against MTX-induced testicular toxicity.
- The protective mechanisms involve antioxidant and anti-inflammatory actions, along with modulation of the p-p38 MAPK signaling pathway.
- Lemon balm extract holds potential as a therapeutic adjunct for mitigating chemotherapy-induced reproductive toxicity.
