Hesperidin attenuates radiation-induced ovarian failure in rats: Emphasis on TLR-4/NF-ĸB signaling pathway

IF 3.3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicology and applied pharmacology Pub Date : 2024-09-24 DOI:10.1016/j.taap.2024.117111

Doaa H. Mohamed , Riham S. Said , Dina H. Kassem , Amany M. Gad , Ebtehal El-Demerdash , Eman M. Mantawy

{"title":"Hesperidin attenuates radiation-induced ovarian failure in rats: Emphasis on TLR-4/NF-ĸB signaling pathway","authors":"Doaa H. Mohamed , Riham S. Said , Dina H. Kassem , Amany M. Gad , Ebtehal El-Demerdash , Eman M. Mantawy","doi":"10.1016/j.taap.2024.117111","DOIUrl":null,"url":null,"abstract":"<div><div>Young women suffering from premature ovarian failure after radiotherapy carry a huge burden in the field of cancer therapy including reproductive loss, emotional stress, and physical troubles that reduce their long-term quality of life. Hesperidin (HSP) exhibited antioxidant, anti-inflammatory, and anti-apoptotic properties. HSP enhanced in vitro follicular maturation and preserved in vivo ovarian stockpile. In this research, the role of HSP in radiation-induced POF in rats was investigated besides ascertaining its underlying mechanisms. Female Sprague-Dawley rats were arbitrarily allocated into four groups: control-group, ϒ-irradiated-group (3.2 Gy once on the 7th day), HSP-group (100 mg/kg, orally for 10 days), and HSP/ϒ-irradiated-group (ϒ-radiation was applied one hour after HSP). At the end of experiment, the whole ovaries were collected for histological and biochemical analyses. Administration of HSP preserved the ovarian histoarchitecture and follicular stock, retained ovarian weight, and conserved serum estradiol and AMH levels following radiation exposure. HSP ameliorated the ovarian oxidative damage mediated by radiation through augmenting the activities of glutathione peroxidase, glutathione reductase, and catalase antioxidant enzymes. HSP exhibited remarkable anti-inflammatory activity by downregulating the expression of ovarian TLR-4, NF-ĸB, and TNF-α. Moreover, HSP suppressed the apoptotic machinery triggered by radiation by reducing p53 and Bax while increasing Bcl-2 mRNA expressions alongside diminishing caspase-3 expression. Additionally, HSP regulated estrous cycle disorder of irradiated rats and improved their reproductive capacity reflected by enhancing pregnancy outcomes. Therefore, HSP represents an appealing candidate as an adjunct remedy for female cancer patients during radiotherapy protocols owing to its antioxidant, anti-inflammatory, anti-apoptotic, and hormone-regulatory effects.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"492 ","pages":"Article 117111"},"PeriodicalIF":3.3000,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology and applied pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0041008X24003107","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

Young women suffering from premature ovarian failure after radiotherapy carry a huge burden in the field of cancer therapy including reproductive loss, emotional stress, and physical troubles that reduce their long-term quality of life. Hesperidin (HSP) exhibited antioxidant, anti-inflammatory, and anti-apoptotic properties. HSP enhanced in vitro follicular maturation and preserved in vivo ovarian stockpile. In this research, the role of HSP in radiation-induced POF in rats was investigated besides ascertaining its underlying mechanisms. Female Sprague-Dawley rats were arbitrarily allocated into four groups: control-group, ϒ-irradiated-group (3.2 Gy once on the 7th day), HSP-group (100 mg/kg, orally for 10 days), and HSP/ϒ-irradiated-group (ϒ-radiation was applied one hour after HSP). At the end of experiment, the whole ovaries were collected for histological and biochemical analyses. Administration of HSP preserved the ovarian histoarchitecture and follicular stock, retained ovarian weight, and conserved serum estradiol and AMH levels following radiation exposure. HSP ameliorated the ovarian oxidative damage mediated by radiation through augmenting the activities of glutathione peroxidase, glutathione reductase, and catalase antioxidant enzymes. HSP exhibited remarkable anti-inflammatory activity by downregulating the expression of ovarian TLR-4, NF-ĸB, and TNF-α. Moreover, HSP suppressed the apoptotic machinery triggered by radiation by reducing p53 and Bax while increasing Bcl-2 mRNA expressions alongside diminishing caspase-3 expression. Additionally, HSP regulated estrous cycle disorder of irradiated rats and improved their reproductive capacity reflected by enhancing pregnancy outcomes. Therefore, HSP represents an appealing candidate as an adjunct remedy for female cancer patients during radiotherapy protocols owing to its antioxidant, anti-inflammatory, anti-apoptotic, and hormone-regulatory effects.

Abstract Image

查看原文本刊更多论文

橙皮甙可减轻辐射诱导的大鼠卵巢功能衰竭：强调TLR-4/NF-ĸB信号通路

放疗后卵巢功能早衰的年轻女性在癌症治疗领域承受着巨大的负担，包括生殖能力丧失、情绪压力和身体不适，这些都降低了她们的长期生活质量。橙皮甙（HSP）具有抗氧化、抗炎和抗细胞凋亡的特性。HSP 可提高体外卵泡成熟度，并保护体内卵巢储备。在这项研究中，除了确定其基本机制外，还调查了 HSP 在辐射诱导的大鼠 POF 中的作用。将雌性 Sprague-Dawley 大鼠任意分为四组：对照组、ϒ-辐照组（第 7 天照射一次，每次 3.2 Gy）、HSP 组（100 mg/kg，口服 10 天）和 HSP/ϒ- 辐照组（HSP 后一小时照射ϒ）。实验结束后，收集整个卵巢进行组织学和生化分析。在辐照后，HSP保留了卵巢组织结构和卵泡存量，保持了卵巢重量，并维持了血清雌二醇和AMH水平。HSP 通过增强谷胱甘肽过氧化物酶、谷胱甘肽还原酶和过氧化氢酶等抗氧化酶的活性，改善了辐射对卵巢造成的氧化损伤。HSP 通过下调卵巢 TLR-4、NF-ĸB 和 TNF-α 的表达，表现出明显的抗炎活性。此外，HSP 通过减少 p53 和 Bax，同时增加 Bcl-2 mRNA 的表达和减少 caspase-3 的表达，抑制了辐射引发的细胞凋亡机制。此外，HSP 还能调节辐照大鼠的发情周期紊乱，并通过提高妊娠率来提高其生殖能力。因此，由于 HSP 具有抗氧化、抗炎、抗凋亡和激素调节作用，它是女性癌症患者在接受放射治疗期间的一种有吸引力的辅助疗法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Toxicology and applied pharmacology 医学-毒理学

CiteScore

6.80

自引率

2.60%

发文量

309

审稿时长

32 days

期刊介绍： Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.