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香芹酚和百里香酚调节 TNF-α 和 IGF-1 信号在放射治疗诱导的卵巢衰竭中的串扰。

Carvacrol and Thymol Modulate the Cross-Talk between TNF- and IGF-1 Signaling in Radiotherapy-Induced Ovarian Failure.

机构信息

Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.

Department of Pharmaceutical Sciences, Faculty of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

出版信息

Oxid Med Cell Longev. 2019 Aug 20;2019:3173745. doi: 10.1155/2019/3173745. eCollection 2019.

DOI:10.1155/2019/3173745
PMID:31531182
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6721489/
Abstract

Premature ovarian failure (POF) is a common cause of infertility in premenopausal women who are unavoidably exposed to cytotoxic therapy. Radiotherapy is one of the most effective cytotoxic treatments. However, the radiosensitivity of ovarian tissues limits its therapeutic outcome and results in the depletion of the primordial follicle and loss of fertility. Therefore, the need for an effective radioprotective therapy is evident especially when none of the current clinically used modalities for radioprotection succeeds efficiently. The present study investigated the potential radioprotective effect of carvacrol (CAR) (80 mg) or thymol (80 mg) on gamma- (-) irradiation-induced ovarian damage as well as their role in the cross-talk between IGF-1 and TNF- signaling and antioxidative activity. In immature female Wister rats, a single dose of whole-body irradiation (3.2 Gy, LD) produced considerable ovarian damage, which was evident by histopathological findings and hormonal changes. Interestingly, pretreatment with CAR or thymol significantly enhanced the follicular development and restored the anti-Mullerian hormone (AMH), E2, and FSH levels. Both essential oils improved the irradiation-mediated oxidative stress and reduction in proliferating cell nuclear antigen (PCNA) expression. Moreover, irradiated rats exhibited an inverse relationship between IGF-1 and TNF- levels two days post irradiation, which was further inverted by the pretreatment with CAR and thymol and ought to contribute in their radioprotective mechanisms. In conclusion, CAR and thymol showed a radioprotective effect and rescued the ovarian reserve mainly through counteracting oxidative stress and the dysregulated cross-talk between IGF-1 and TNF-.

摘要

卵巢早衰(POF)是一种常见的导致育龄期前女性不孕的疾病,这些女性不可避免地会受到细胞毒性治疗。放射治疗是最有效的细胞毒性治疗之一。然而,卵巢组织对放射线的敏感性限制了其治疗效果,导致原始卵泡耗竭和生育能力丧失。因此,需要一种有效的放射防护治疗,特别是当目前临床使用的放射防护方法都不能有效地发挥作用时。本研究探讨了香芹酚(CAR)(80mg)或百里香酚(80mg)对γ(-)辐射诱导的卵巢损伤的潜在放射防护作用,以及它们在 IGF-1 和 TNF-信号转导的交叉对话和抗氧化活性中的作用。在未成熟雌性 Wister 大鼠中,单次全身照射(3.2Gy,LD)会导致明显的卵巢损伤,这可以通过组织病理学发现和激素变化来证明。有趣的是,CAR 或百里香酚预处理显著增强了卵泡发育,并恢复了抗苗勒管激素(AMH)、E2 和 FSH 水平。两种精油均改善了照射介导的氧化应激和增殖细胞核抗原(PCNA)表达的减少。此外,照射后的大鼠 IGF-1 和 TNF-水平呈负相关,CAR 和百里香酚预处理进一步逆转了这种关系,这可能有助于它们的放射防护机制。总之,CAR 和百里香酚表现出放射防护作用,并通过抵抗氧化应激和 IGF-1 与 TNF-之间失调的交叉对话来挽救卵巢储备。

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