L-Ergothioneine attenuates methotrexate-induced testicular injury in rats by restoring redox balance, SIRT1/PGC-1α signalling and mitochondrial quality control, and by normalising the miR-222–3p axis
Reproductive Toxicology, cilt.147, 2027 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 147
- Basım Tarihi: 2027
- Doi Numarası: 10.1016/j.reprotox.2026.109400
- Dergi Adı: Reproductive Toxicology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chimica, EMBASE, Environment Index, MEDLINE, Academic Search Ultimate (EBSCO)
- Anahtar Kelimeler: L-ergothioneine, Methotrexate, Mitochondrial dysfunction, Testicular toxicity, TPTE/miR-222–3p/TRAF7 axis
- Uşak Üniversitesi Adresli: Evet
Özet
Methotrexate (MTX), an antimetabolite used in cancer chemotherapy and inflammatory diseases, may induce testicular injury. This study investigated acute MTX-associated changes in testicular hormonal, molecular, histopathological, and spermatological parameters and evaluated the effects of L-ergothioneine (LERG). Twenty-eight male Wistar albino rats were randomly assigned to four groups (n = 7): Control, LERG, MTX, and MTX + LERG. MTX was administered as a single intraperitoneal dose (20 mg/kg), while LERG was administered orally (35 mg/kg/day) for five days. Serum testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were measured, alongside molecular, histopathological, immunohistochemical, immunofluorescence, and spermatological assessments. MTX exposure was associated with decreased serum testosterone and increased FSH and LH levels. Alterations were observed in inflammation-related markers (NF-κB, TNF-α, IL-1β, and NLRP3), oxidative stress-related markers (MDA, CAT, GPx), mitochondrial function-related markers (SIRT1, FoxO3a, AMPK, MFN2, and PGC-1α), mitophagy-related proteins (PINK1 and Parkin), and DNA damage-related markers (γH2AX, p53, p21, and GADD45). Changes in StAR, SOX9, DAZL, and the TPTE/miR-222–3p/TRAF7 axis were accompanied by histopathological abnormalities and altered sperm parameters. Concurrent LERG administration attenuated some MTX-associated changes, although the effects varied across the evaluated parameters. These findings indicate that acute MTX exposure is associated with hormonal, molecular, and histopathological alterations in the testis. LERG may modify some of these changes; however, further studies are needed to clarify its mechanisms of action and potential implications for long-term reproductive health.