Evren Üstüner, Ebru Yıldırım, Hasan Ceyhun Macun, Hüsamettin Ekici, Yaşar Şahin, Enes Güncüm, Tuğçe Anteplioğlu, Taha Burak Elifoğlu, Esra Bozkaya
{"title":"N-乙酰半胱氨酸对多柔比星诱发的大鼠卵巢和子宫毒性作用的超声和组织病理学研究","authors":"Evren Üstüner, Ebru Yıldırım, Hasan Ceyhun Macun, Hüsamettin Ekici, Yaşar Şahin, Enes Güncüm, Tuğçe Anteplioğlu, Taha Burak Elifoğlu, Esra Bozkaya","doi":"10.1186/s13048-024-01459-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>This study aimed to investigate the mitigating effect of N-acetylcysteine (NAC) on doxorubicin (DOX)-induced ovarian and uterine toxicity in rats using laboratory tests, ultrasonographic (US) imaging, and histopathology analysis.</p><p><strong>Methods: </strong>Forty-eight rats were divided into six groups (n = 8) as follows: Group A (control) (0.5 mL saline administered intraperitoneally [IP]), Group B (a single 10 mg/kg dose of DOX administered IP on day 1), Group C (a single 10 mg/kg dose of DOX administered IP 24 h before sacrifice), Group D (100 mg/kg of NAC administered IP for 21 days), Group E ( a single 10 mg/kg dose of DOX administered IP on day 1 and 100 mg/kg of NAC administered IP for 21 days), and Group F (100 mg/kg of NAC administered IP for 21 days and a single 10 mg/kg dose of DOX administered IP 24 h before sacrifice). The ovaries were examined using B-mode US on days 1, 14, and 21, and the histopathological examinations of the ovaries and the uterus were undertaken after sacrifice on day 22.</p><p><strong>Results: </strong>Histomorphological analyses showed that ovarian weight decreased after DOX administration in Group B but not in Group E. US revealed a transient increase in ovarian size in Group B and E, reverting to baseline levels over time, as well as a progressive increase in peritoneal fluid in Groups B and E. Group B exhibited a significant decrease in the thickness of the endometrium and myometrium and uterine cornual length, which was not observed in Group E. Histopathological examination showed that DOX caused a decline in follicular count, especially in primordial, secondary, and Graafian follicles, and resulted in follicular atresia, predominantly in Group B. Destructive degeneration/necrosis and vascular changes were most prominently seen in the corpus luteum of Groups C and B. In NAC-treated rats (Groups E and F), although germ cell damage was present, atretic follicles and vascular changes, such as hyperemia and congestion, were reduced. The anti-müllerian hormone (AMH) level was the highest in Group F.</p><p><strong>Conclusions: </strong>NAC, an antioxidant, attenuated DOX-induced gonadotoxicity in rats.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":null,"pages":null},"PeriodicalIF":3.8000,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214216/pdf/","citationCount":"0","resultStr":"{\"title\":\"Ultrasonographic and histopathological investigation of the effect of N-acetylcysteine on doxorubicin-induced ovarian and uterine toxicity in rats.\",\"authors\":\"Evren Üstüner, Ebru Yıldırım, Hasan Ceyhun Macun, Hüsamettin Ekici, Yaşar Şahin, Enes Güncüm, Tuğçe Anteplioğlu, Taha Burak Elifoğlu, Esra Bozkaya\",\"doi\":\"10.1186/s13048-024-01459-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>This study aimed to investigate the mitigating effect of N-acetylcysteine (NAC) on doxorubicin (DOX)-induced ovarian and uterine toxicity in rats using laboratory tests, ultrasonographic (US) imaging, and histopathology analysis.</p><p><strong>Methods: </strong>Forty-eight rats were divided into six groups (n = 8) as follows: Group A (control) (0.5 mL saline administered intraperitoneally [IP]), Group B (a single 10 mg/kg dose of DOX administered IP on day 1), Group C (a single 10 mg/kg dose of DOX administered IP 24 h before sacrifice), Group D (100 mg/kg of NAC administered IP for 21 days), Group E ( a single 10 mg/kg dose of DOX administered IP on day 1 and 100 mg/kg of NAC administered IP for 21 days), and Group F (100 mg/kg of NAC administered IP for 21 days and a single 10 mg/kg dose of DOX administered IP 24 h before sacrifice). 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引用次数: 0
摘要
研究背景本研究旨在通过实验室测试、超声成像(US)和组织病理学分析,探讨N-乙酰半胱氨酸(NAC)对多柔比星(DOX)诱导的大鼠卵巢和子宫毒性的缓解作用:将 48 只大鼠分为以下 6 组(n = 8):A 组(对照组)(0.5毫升生理盐水腹腔注射[IP])、B组(第1天腹腔注射单次10毫克/千克剂量的DOX)、C组(牺牲前24小时腹腔注射单次10毫克/千克剂量的DOX)、D组(腹腔注射100毫克/千克NAC,连续21天)、E组(第 1 天给予单次 10 毫克/千克剂量的 DOX IP,并给予 100 毫克/千克 NAC IP,共 21 天)和 F 组(给予 100 毫克/千克 NAC IP,共 21 天,并在牺牲前 24 小时给予单次 10 毫克/千克剂量的 DOX IP)。在第 1、14 和 21 天使用 B 型 US 对卵巢进行检查,在第 22 天牺牲后对卵巢和子宫进行组织病理学检查:组织形态学分析表明,服用 DOX 后,B 组卵巢重量减少,而 E 组卵巢重量没有减少。B 组和 E 组的 US 显示卵巢体积短暂增大,随着时间的推移恢复到基线水平,B 组和 E 组的腹腔积液逐渐增加。组织病理学检查显示,DOX导致卵泡数量减少,尤其是原始卵泡、次级卵泡和Graafian卵泡,并导致卵泡闭锁,主要发生在B组;C组和B组黄体的破坏性变性/坏死和血管变化最为显著。F 组的抗苗勒氏管激素(AMH)水平最高:结论:抗氧化剂 NAC 可减轻 DOX 诱导的大鼠性腺毒性。
Ultrasonographic and histopathological investigation of the effect of N-acetylcysteine on doxorubicin-induced ovarian and uterine toxicity in rats.
Background: This study aimed to investigate the mitigating effect of N-acetylcysteine (NAC) on doxorubicin (DOX)-induced ovarian and uterine toxicity in rats using laboratory tests, ultrasonographic (US) imaging, and histopathology analysis.
Methods: Forty-eight rats were divided into six groups (n = 8) as follows: Group A (control) (0.5 mL saline administered intraperitoneally [IP]), Group B (a single 10 mg/kg dose of DOX administered IP on day 1), Group C (a single 10 mg/kg dose of DOX administered IP 24 h before sacrifice), Group D (100 mg/kg of NAC administered IP for 21 days), Group E ( a single 10 mg/kg dose of DOX administered IP on day 1 and 100 mg/kg of NAC administered IP for 21 days), and Group F (100 mg/kg of NAC administered IP for 21 days and a single 10 mg/kg dose of DOX administered IP 24 h before sacrifice). The ovaries were examined using B-mode US on days 1, 14, and 21, and the histopathological examinations of the ovaries and the uterus were undertaken after sacrifice on day 22.
Results: Histomorphological analyses showed that ovarian weight decreased after DOX administration in Group B but not in Group E. US revealed a transient increase in ovarian size in Group B and E, reverting to baseline levels over time, as well as a progressive increase in peritoneal fluid in Groups B and E. Group B exhibited a significant decrease in the thickness of the endometrium and myometrium and uterine cornual length, which was not observed in Group E. Histopathological examination showed that DOX caused a decline in follicular count, especially in primordial, secondary, and Graafian follicles, and resulted in follicular atresia, predominantly in Group B. Destructive degeneration/necrosis and vascular changes were most prominently seen in the corpus luteum of Groups C and B. In NAC-treated rats (Groups E and F), although germ cell damage was present, atretic follicles and vascular changes, such as hyperemia and congestion, were reduced. The anti-müllerian hormone (AMH) level was the highest in Group F.
Conclusions: NAC, an antioxidant, attenuated DOX-induced gonadotoxicity in rats.
期刊介绍:
Journal of Ovarian Research is an open access, peer reviewed, online journal that aims to provide a forum for high-quality basic and clinical research on ovarian function, abnormalities, and cancer. The journal focuses on research that provides new insights into ovarian functions as well as prevention and treatment of diseases afflicting the organ.
Topical areas include, but are not restricted to:
Ovary development, hormone secretion and regulation
Follicle growth and ovulation
Infertility and Polycystic ovarian syndrome
Regulation of pituitary and other biological functions by ovarian hormones
Ovarian cancer, its prevention, diagnosis and treatment
Drug development and screening
Role of stem cells in ovary development and function.