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蒲桃果实提取物和槲皮素通过miRNA - 204 - 5p介导的Bcl - 2上调以及Bax/Caspase 9/Caspase 3下调减轻镉诱导的大鼠卵巢细胞凋亡。

Syzygium cumini Fruit Extract and Quercetin Ameliorate Cadmium-Induced Ovarian Apoptosis in Rats Via miRNA- 204 - 5p-Mediated Bcl- 2 Upregulation and Bax/Caspase 9/Caspase 3 Downregulation.

作者信息

Abdel-Badeea Walaa I E, Abdel-Wahab Ahmed, Mahmoud Ahmed A, Abdel-Razik Abdel-Razik H, Attia Eman Z, Abdelmohsen Usama R, Hassanin Kamel M A

机构信息

Biochemistry Department, Faculty of Veterinary Medicine, Minia University, 61519, Minia, Egypt.

Physiology Department, Faculty of Veterinary Medicine, Minia University, 61519, Minia, Egypt.

出版信息

Biol Trace Elem Res. 2025 May 14. doi: 10.1007/s12011-025-04632-y.

DOI:10.1007/s12011-025-04632-y
PMID:40360878
Abstract

The correlation between exposure to environmental pollutants and adverse impacts on fertility has been documented. Cadmium (Cd) is one of the most toxic elements that impairs female reproductive capacity. Syzygium cumini is a plant that contains polyphenols with strong antioxidant properties. Our study aimed to investigate the possible protective effects of Syzygium cumini fruit extract (SCFE) and quercetin (QU) against Cd-induced ovarian toxicity and apoptosis in rats assisted by measuring oxidative stress markers, hormonal profile, intrinsic apoptotic pathway, miRNA-204-5p, and histopathology. For that, 45 adult female rats were divided randomly into five groups; control, cadmium chloride (CdCl), CdCl + QU, CdCl + SCFE200, and CdCl + SCFE400, and the experiment lasted 35 days. Cadmium exposure induced irregular estrus cycle, and oxidative challenges, as evidenced by increased malondialdehyde and decreased antioxidant indicators that include superoxide dismutase, catalase and reduced glutathione, and hormonal imbalances, including reduced follicle-stimulating hormone, luteinizing hormone, anti-mullarian hormone, estrogen, and progesterone levels. Additionally, Cd triggered ovarian apoptosis through upregulating miRNA- 204 - 5p expression that in turn downregulated Bcl- 2 and upregulated the members of intrinsic mitochondrial apoptotic pathway including Bax and caspases 3, 9. The histopathological findings, morphometric and lesion scoring in ovarian, and uterine tissues confirmed the negative impacts of Cd. Interestingly, treatment with QU or SCFE, especially at the higher dose (400 mg/kg), significantly ameliorated these Cd-induced adverse effects, suggesting their potential as protective agents against ovarian toxicity.

摘要

环境污染物暴露与生育能力的不良影响之间的相关性已有文献记载。镉(Cd)是损害女性生殖能力的最具毒性的元素之一。蒲桃是一种含有具有强大抗氧化特性的多酚的植物。我们的研究旨在通过测量氧化应激标志物、激素水平、内在凋亡途径、miRNA - 204 - 5p和组织病理学,研究蒲桃果实提取物(SCFE)和槲皮素(QU)对镉诱导的大鼠卵巢毒性和细胞凋亡的可能保护作用。为此,将45只成年雌性大鼠随机分为五组:对照组、氯化镉(CdCl)组、CdCl + QU组、CdCl + SCFE200组和CdCl + SCFE400组,实验持续35天。镉暴露导致发情周期不规律和氧化应激,表现为丙二醛增加,超氧化物歧化酶、过氧化氢酶和还原型谷胱甘肽等抗氧化指标降低,以及激素失衡,包括促卵泡激素、促黄体生成素、抗苗勒管激素、雌激素和孕酮水平降低。此外,镉通过上调miRNA - 204 - 5p表达触发卵巢细胞凋亡,进而下调Bcl - 2并上调包括Bax和半胱天冬酶3、9在内线粒体内在凋亡途径的成员。卵巢和子宫组织的组织病理学检查结果、形态计量学和病变评分证实了镉的负面影响。有趣的是,用QU或SCFE治疗,尤其是高剂量(400 mg/kg)时,可显著改善这些镉诱导的不良反应,表明它们作为抗卵巢毒性保护剂的潜力。

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本文引用的文献

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Design and development of locust bean gum-endowed/Phyllanthus reticulatus anthocyanin- functionalized biogenic gold nanosystem for enhanced antioxidative and anticancer chemotherapy.用于增强抗氧化和抗癌化疗的刺槐豆胶赋予/余甘子花青素功能化生物源金纳米系统的设计与开发
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