Protective effect of N-acetylcysteine in doxorubicininduced primary ovarian failure in female rats

dc.contributor.authorAslan, İlke Özer
dc.contributor.authorÖz, Mehmet
dc.contributor.authorErdal, Hüseyin
dc.contributor.authorKaraboğa, İhsan
dc.contributor.authorDoğan, Mehmet
dc.date.accessioned2025-09-23T10:43:45Z
dc.date.available2025-09-23T10:43:45Z
dc.date.issued2025
dc.departmentTıp Fakültesi
dc.description.abstractN-acetylcysteine (NAC), an aminothiol compound, eliminates free radicals and enhances glutathione (GSH) synthesis, thereby strengthening intracellular antioxidant defenses. Although its protective effects against ovarian injury have been reported, its efficacy in doxorubicin (DOX)-induced ovarian failure has not been demonstrated. This study aimed to investigate whether NAC exerts a protective role against DOX-induced ovarian toxicity in female rats. Materials and methods: Twenty-one adult female rats were randomly assigned to three groups: Control, DOX (10 mg/kg, i.p., single dose), and DOX+NAC (150 mg/kg, i.p., for 5 days; DOX administered on day 3, one hour after NAC). Serum and tissue oxidative stress parameters, histopathological changes, proliferating cell nuclear antigen (PCNA) immunoreactivity, and TUNEL assay were evaluated. Results: DOX significantly reduced serum anti-M & uuml;llerian hormone (AMH) (6.75 -> 5.31 ng/mL; p<0.001) and GSH (422.64 -> 280.98 mg/L; p<0.001), while increasing tumor necrosis factor alpha (TNF-alpha) (175.87 -> 260.77 ng/L; p<0.001) and total oxidant status (TOS) (7.18 -> 11.84 U/mL; p=0.002). NAC treatment reversed these alterations, namely: AMH (6.51 ng/mL; p=0.004), GSH (363.86 mg/L; p=0.018), TNF-alpha (184.55 ng/L; p<0.001), TOS (7.88 U/mL; p=0.003). In ovarian tissue, DOX reduced GSH (123.63 -> 80.64 mg/L; p=0.001) and total antioxidant status (14.88 -> 10.57 U/mL; p<0.001), while elevating TOS (7.14 -> 12.64 U/mL; p<0.001) and caspase-3 (2.06 -> 3.14 ng/mL; p<0.001). NAC significantly improved all these parameters (p <= 0.005). Histologically, DOX caused edema, hemorrhage, infiltration, and a reduction in the percentage of healthy follicles, whereas NAC markedly ameliorated these alterations. Furthermore, NAC enhanced PCNA expression and reduced TUNEL-positive granulosa cells, supporting its anti-apoptotic effect. Conclusion: NAC preserved ovarian reserve and follicular integrity by suppressing oxidative stress, inflammation, and apoptosis induced by DOX. These findings highlight NAC as a promising protective agent against chemotherapy-induced ovarian toxicity.
dc.identifier.doi10.4274/tjod.galenos.2025.71654
dc.identifier.endpage274
dc.identifier.issn2149-9322 / 2149-9330
dc.identifier.issue3
dc.identifier.pmid40851422
dc.identifier.startpage266
dc.identifier.urihttps://doi.org/10.4274/tjod.galenos.2025.71654
dc.identifier.urihttps://hdl.handle.net/20.500.12451/14523
dc.identifier.volume22
dc.identifier.wosWOS:001567834700001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakPubMed
dc.indekslendigikaynakWeb of Science
dc.institutionauthorÖz, Mehmet
dc.institutionauthorErdal, Hüseyin
dc.language.isoen
dc.publisherGalenos Publishing House
dc.relation.ispartofTurkish Journal of Obstetrics and Gynecology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectDoxorubicin
dc.subjectInfertility
dc.subjectN-acetylcysteine
dc.subjectOvarian Function
dc.subjectPrimary Ovarian Failure
dc.titleProtective effect of N-acetylcysteine in doxorubicininduced primary ovarian failure in female rats
dc.typeArticle

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