Özer Aslan İlke, Öz Mehmet, Erdal Hüseyin, Karaboğa İhsan, Doğan Mehmet
Tekirdağ Namık Kemal University Faculty of Medicine, Department of Obstetrics and Gynecology, Tekirdağ, Türkiye.
Assisted Reproductive Technologies Unit, Acıbadem Maslak Hospital, İstanbul, Türkiye.
Turk J Obstet Gynecol. 2025 Sep 5;22(3):266-274. doi: 10.4274/tjod.galenos.2025.71654. Epub 2025 Aug 25.
N-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.
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.
DOX significantly reduced serum anti-Müllerian 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-α) (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-α (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.
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.
N-乙酰半胱氨酸（NAC）是一种氨基硫醇化合物，可清除自由基并增强谷胱甘肽（GSH）的合成，从而加强细胞内抗氧化防御。尽管已有报道其对卵巢损伤具有保护作用，但其在阿霉素（DOX）诱导的卵巢功能衰竭中的疗效尚未得到证实。本研究旨在探讨NAC对雌性大鼠DOX诱导的卵巢毒性是否具有保护作用。
将21只成年雌性大鼠随机分为三组：对照组、DOX组（10 mg/kg，腹腔注射，单次剂量）和DOX+NAC组（150 mg/kg，腹腔注射，共5天；DOX在第3天给药，在NAC给药1小时后）。评估血清和组织氧化应激参数、组织病理学变化、增殖细胞核抗原（PCNA）免疫反应性和TUNEL检测。
DOX显著降低血清抗苗勒管激素（AMH）（6.75→5.31 ng/mL；p<0.001）和GSH（422.64→280.98 mg/L；p<0.001），同时增加肿瘤坏死因子α（TNF-α）（175.87→260.77 ng/L；p<0.001）和总氧化剂状态（TOS）（7.18→11.84 U/mL；p=0.002）。NAC治疗逆转了这些改变，即：AMH（6.51 ng/mL；p=0.004）、GSH（363.86 mg/L；p=0.018）、TNF-α（184.55 ng/L；p<0.001）、TOS（7.88 U/mL；p=0.003）。在卵巢组织中，DOX降低了GSH（123.63→80.64 mg/L；p=0.001）和总抗氧化状态（14.88→10.57 U/mL；p<0.001），同时升高了TOS（7.14→12.64 U/mL；p<0.001）和半胱天冬酶-3（2.06→3.14 ng/mL；p<0.001）。NAC显著改善了所有这些参数（p≤0.005）。组织学上，DOX导致水肿、出血、浸润以及健康卵泡百分比降低，而NAC明显改善了这些改变。此外，NAC增强了PCNA表达并减少了TUNEL阳性颗粒细胞，支持其抗凋亡作用。
NAC通过抑制DOX诱导的氧化应激、炎症和凋亡来保留卵巢储备和卵泡完整性。这些发现突出了NAC作为一种有前景的抗化疗诱导卵巢毒性的保护剂。
