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孕期接触苯并(a)芘对幼龄大鼠子代的肝毒性作用,以及阿托伐他汀的保护作用。

Hepatotoxicity in young adult rat offspring after prenatal exposure to benzo(a)pyrene, and protective effect of atorvastatin.

机构信息

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

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

出版信息

Birth Defects Res. 2022 Jul 1;114(11):551-558. doi: 10.1002/bdr2.2043. Epub 2022 May 20.

Abstract

OBJECTIVES

Benzo[a]pyrene (BaP) is an environmental contaminant that interrupts the antioxidant defense and thus leads to oxidative stress and DNA damage in the liver. Atorvastatin (ATV) for reducing cholesterol has antioxidant and anti-apoptotic activities. This study investigated the effects of prenatal exposure of BaP on liver toxicity and the protective role of ATV in reducing liver toxicity.

MATERIALS AND METHODS

In this study, rats were distributed randomly to seven groups: I. Saline control; II. ATV (10 mg/kg); III. Corn oil; IV and V. BaP (10 and 20 mg/kg); VI and VII. ATV + BaP (10 and 20 mg/kg). BaP and ATV were administrated from gestation day 7-16 (GD7-GD16), orally. Ten weeks after the birth, female offspring were examined for oxidative stress markers, liver enzymes, and histology.

RESULTS

Data revealed that BaP significantly induced oxidative stress (decreased glutathione and increased malondialdehyde level), and disrupted the tissue structure of the liver. Moreover, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase increased in the offspring. ATV treatment along with BaP during gestation was able to bring the antioxidant status and serum liver enzymes levels relatively close to normal. As well as, histological findings showed that ATV was able to improve liver tissue structure caused by BaP.

CONCLUSION

Based on the above studies we concluded that ATV at a low dose during gestation was able to reduce liver damage caused by BaP with antioxidant properties.

摘要

目的

苯并[a]芘(BaP)是一种环境污染物,它会中断抗氧化防御系统,从而导致肝脏的氧化应激和 DNA 损伤。阿托伐他汀(ATV)具有降低胆固醇的作用,同时具有抗氧化和抗凋亡作用。本研究旨在探讨产前暴露于 BaP 对肝脏毒性的影响,以及 ATV 降低肝脏毒性的保护作用。

材料和方法

在这项研究中,大鼠被随机分为七组:I. 生理盐水对照;II. ATV(10mg/kg);III. 玉米油;IV 和 V. BaP(10 和 20mg/kg);VI 和 VII. ATV+BaP(10 和 20mg/kg)。BaP 和 ATV 从妊娠第 7-16 天(GD7-GD16)开始口服给药。出生后 10 周,雌性后代接受氧化应激标志物、肝酶和组织学检查。

结果

数据显示,BaP 显著诱导了氧化应激(谷胱甘肽减少,丙二醛水平升高),破坏了肝脏的组织结构。此外,丙氨酸氨基转移酶、天冬氨酸氨基转移酶和碱性磷酸酶在后代中增加。在妊娠期间同时给予 ATV 和 BaP 治疗能够使抗氧化状态和血清肝酶水平相对接近正常。组织学发现表明,ATV 能够改善 BaP 引起的肝脏组织结构异常。

结论

基于上述研究,我们得出结论,在妊娠期间给予低剂量的 ATV 能够通过抗氧化作用减轻 BaP 引起的肝脏损伤。

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