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孕期暴露于苯并[a]芘对卵巢毒性和生殖功能障碍的影响:阿托伐他汀在胚胎期的保护作用。

Effect of prenatal exposure to Benzo[a]pyrene on ovarian toxicity and reproductive dysfunction: Protective effect of atorvastatin in the embryonic period.

机构信息

Department of Anatomy, Faculty of Medicine, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

Student Research Committee, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

出版信息

Environ Toxicol. 2021 Aug;36(8):1683-1693. doi: 10.1002/tox.23164. Epub 2021 May 12.

Abstract

As an environmental contaminant, Benzo[a]pyrene (B[a]P; BaP) disrupts the antioxidant signaling and thus leads to the induction of oxidative stress and the damage of DNA in the ovary. low-dose atorvastatin (ATV) has antioxidant and anti-apoptotic properties. The present study aimed to survey the effects of prenatal exposure to BaP on ovarian toxicity and also to investigate the protective role of ATV in reducing ovarian toxicity. In this study, rats were divided into seven groups: control, ATV (10 mg/kg), oil, BaP (10 and 20 mg/kg), and ATV + BaP (10 and 20 mg/kg). BaP and ATV were administrated from gestation day 7-16 (GD7 to GD16), orally. 10 weeks after the birth, female offsprings were examined for oxidative stress markers, sex hormones, ovarian and tubular tissue structure, and the apoptosis markers. Data showed that BaP significantly reduced glutathione, increased malondialdehyde level, and disrupted the tissue structure of the ovary. Moreover, estrogen and progesterone levels significantly decreased in the offsprings rats. Also, BaP increased caspase-3 immunoreactivity. Atorvastatin treatment along with BaP in the embryonic period were able to bring the antioxidant status and sex hormones levels relatively close to normal. Besides, histological findings showed that atorvastatin was able to improve ovarian and oviduct abnormalities caused by BaP. Based on the above studies be concluded that atorvastatin in the embryonic during was able to reduce ovarian damage caused by BaP with antioxidant and anti-apoptotic properties.

摘要

作为一种环境污染物,苯并[a]芘(BaP)会破坏抗氧化信号,从而导致卵巢氧化应激和 DNA 损伤。小剂量阿托伐他汀(ATV)具有抗氧化和抗凋亡作用。本研究旨在调查产前暴露于 BaP 对卵巢毒性的影响,并研究 ATV 减少卵巢毒性的保护作用。在这项研究中,大鼠被分为七组:对照组、ATV(10mg/kg)、油、BaP(10 和 20mg/kg)和 ATV+BaP(10 和 20mg/kg)。BaP 和 ATV 从妊娠第 7 天至第 16 天(GD7 至 GD16)口服给药。出生后 10 周,雌性后代接受氧化应激标志物、性激素、卵巢和管状组织结构以及凋亡标志物检查。数据显示,BaP 显著降低了谷胱甘肽水平,增加了丙二醛水平,并破坏了卵巢的组织结构。此外,雌性后代的雌激素和孕激素水平显著下降。同时,caspase-3 免疫反应性增加。胚胎期同时给予阿托伐他汀和 BaP 能够使抗氧化状态和性激素水平相对接近正常。此外,组织学发现表明,阿托伐他汀能够改善 BaP 引起的卵巢和输卵管异常。基于上述研究可以得出结论,阿托伐他汀在胚胎期具有抗氧化和抗凋亡作用,能够减轻 BaP 引起的卵巢损伤。

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