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ω-3脂肪酸可消除他莫昔芬处理的大鼠睾丸中氧化炎症和线粒体功能障碍相关的凋亡反应。

Omega-3 fatty acids abrogates oxido-inflammatory and mitochondrial dysfunction-associated apoptotic responses in testis of tamoxifen-treated rats.

作者信息

Odetayo Adeyemi Fatai, Akhigbe Roland Eghoghosoa, Hamed Moses Agbomhere, Balogun Morufu Eyitayo, Oluwole David Tolulope, Olayaki Luqman Aribidesi

机构信息

Department of Physiology, Faculty of Basic Medical Sciences, Federal University of Health Sciences, Ila Orangun, Nigeria.

Reproductive Biology and Toxicology Research Laboratory, Oasis of Grace Hospital, Osogbo, Nigeria.

出版信息

Front Nutr. 2024 Aug 1;11:1443895. doi: 10.3389/fnut.2024.1443895. eCollection 2024.

Abstract

BACKGROUND

Tamoxifen (TAM) is a widely used drug in patients with gynecomastia and breast cancer. TAM exerts its anticancer effects via its antiestrogenic activities. Unfortunately, TAM has been reported to exert gonadotoxic effects on male testes. Therefore, this study was designed to explore the possible associated mechanisms involved in TAM-induced testicular dysfunction and the possible ameliorative effects of omega-3 fatty acids (O3FA).

METHODOLOGY

Animals were randomly divided into control, O3FA, TAM, and TAM + O3FA. All treatment lasted for 28 days.

RESULTS

TAM exposure impaired sperm qualities (count, motility, and normal morphology) and decreased testicular 3β-HSD and 17β-HSD. It was accompanied by a decline in serum testosterone and an increase in estradiol, luteinizing and follicle-stimulating hormones. These observed alterations were associated with an increase in testicular injury markers, oxido-inflammatory response, and mitochondria-mediated apoptosis. These observed alterations were ameliorated by O3FA treatments.

CONCLUSIONS

O3FA ameliorated TAM-induced testicular dysfunction in male Wistar rats by modulating XO/UA and Nrf2/NF-kb signaling and cytochrome c-mediated apoptosis in TAM-treated rats.

摘要

背景

他莫昔芬(TAM)是一种广泛应用于男性乳房发育症和乳腺癌患者的药物。TAM通过其抗雌激素活性发挥抗癌作用。不幸的是,已有报道称TAM对雄性睾丸具有性腺毒性作用。因此,本研究旨在探讨TAM诱导睾丸功能障碍的可能相关机制以及ω-3脂肪酸(O3FA)可能的改善作用。

方法

将动物随机分为对照组、O3FA组、TAM组和TAM + O3FA组。所有处理持续28天。

结果

暴露于TAM会损害精子质量(数量、活力和正常形态),并降低睾丸3β - HSD和17β - HSD水平。同时伴有血清睾酮水平下降以及雌二醇、黄体生成素和卵泡刺激素水平升高。这些观察到的变化与睾丸损伤标志物增加、氧化炎症反应以及线粒体介导的细胞凋亡有关。O3FA处理可改善这些观察到的变化。

结论

O3FA通过调节TAM处理大鼠中的XO/UA和Nrf2/NF - kb信号通路以及细胞色素c介导的细胞凋亡,改善了TAM诱导的雄性Wistar大鼠睾丸功能障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/535e/11324566/31f121e942e9/fnut-11-1443895-g0001.jpg

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