Agomelatine Protects Cyclophosphamide-Induced Testicular Tissue Damage Despite HPG Axis Suppression in Rats

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dc.contributor.authorKorkmaz, Engin
dc.contributor.authorBeytur, Asiye
dc.contributor.authorTaslidere, Asli
dc.contributor.authorTekin, Suat
dc.date.accessioned2026-04-04T13:35:16Z
dc.date.available2026-04-04T13:35:16Z
dc.date.issued2026
dc.departmentİnönü Üniversitesi
dc.description.abstractThis study aimed to evaluate the prophylactic efficacy of agomelatine (Ago), a potent melatonergic agonist and antioxidant, in preserving testicular integrity against cyclophosphamide (CP)-induced acute toxicity. A preconditioning protocol was established in which rats received Ago (40 mg/kg/day) for 14 consecutive days prior to a single toxic dose of CP (200 mg/kg). The parameters assessed included oxidative stress markers (MDA, GSH-px, SOD, and CAT), inflammatory mediators (TNF-alpha, IL-1 beta, and NF-kappa B), histopathological scores, and the endocrine profile (FSH, LH, and testosterone). CP administration elicited severe oxidative stress, inflammation, and histological degeneration. Ago preconditioning significantly attenuated lipid peroxidation and pro-inflammatory cytokine levels while preserving antioxidant enzyme activities. Furthermore, Ago effectively maintained testicular architecture and sperm concentration. Notably, despite this robust structural protection, significant suppression of serum FSH, LH, and testosterone levels was observed in the Ago-treated groups. Our findings demonstrate that Ago preserves testicular morphology and cellular integrity against CP-induced damage through antioxidant and anti-inflammatory mechanisms. However, this structural protection was accompanied by a significant suppression of the HPG axis at the administered dose. These results indicate that Ago-mediated cytoprotection may occur independently of endocrine homeostasis, underscoring the need for future dose-response studies to identify an optimal therapeutic window that balances peripheral protection with hormonal regulation.
dc.description.sponsorshipInonu University
dc.description.sponsorshipOpen access funding provided by the Scientific and Technological Research Council of Turkiye (TUB & Idot;TAK).
dc.identifier.doi10.1007/s44411-026-00546-w
dc.identifier.endpage1499
dc.identifier.issn0006-9248
dc.identifier.issn1336-0345
dc.identifier.issue4
dc.identifier.scopus2-s2.0-105031410059
dc.identifier.scopusqualityQ2
dc.identifier.startpage1487
dc.identifier.urihttps://doi.org/10.1007/s44411-026-00546-w
dc.identifier.urihttps://hdl.handle.net/11616/109723
dc.identifier.volume127
dc.identifier.wosWOS:001702188300001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherSpringernature
dc.relation.ispartofBratislava Medical Journal
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250329
dc.subjectAgomelatine
dc.subjectCyclophosphamide
dc.subjectInflammation
dc.subjectInfertility
dc.subjectOxidative stress
dc.subjectTesticular toxicity
dc.titleAgomelatine Protects Cyclophosphamide-Induced Testicular Tissue Damage Despite HPG Axis Suppression in Rats
dc.typeArticle

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