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没食子酸通过提高肝脏抗氧化能力和抑制ROS/NFκβ/TNFα炎症途径来治疗大鼠粉尘诱导的非酒精性脂肪性肝病。

Gallic acid treats dust-induced NAFLD in rats by improving the liver's anti-oxidant capacity and inhibiting ROS/NFκβ/TNFα inflammatory pathway.

作者信息

Fanaei Hafseh, Mard Seyyed Ali, Sarkaki Alireza, Goudarzi Gholamreza, Khorsandi Layasadat

机构信息

Physiology Research Center (PRC), Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Persian Gulf's Physiology Research Center (PRC), Department of Physiology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

出版信息

Iran J Basic Med Sci. 2021 Feb;24(2):240-247. doi: 10.22038/IJBMS.2021.51036.11603.

Abstract

OBJECTIVES

The burden of disease and death related to environmental pollution is becoming a major public health challenge, especially in developing countries. This study was designed to investigate the effect of dust exposure on liver function and its structure in rats. Gallic acid (GA) as a potent anti-oxidant was also used to treat NAFLD in rats exposed to dust.

MATERIALS AND METHODS

Twenty-four rats were randomly assigned into 3 groups: CA, Dust+N/S (after stopping dust exposure, rats received normal saline as vehicle, 1 ml, orally for 14 consecutive days), and Dust+GA (after stopping dust exposure, rats received GA at 100 mg/kg, orally for 14 consecutive days). Rats were exposed to CA/ dust for 6 weeks on alternate days. At the end of experiments, rats were anesthetized, their blood samples and liver sections were taken to perform molecular, biomedical and histopathological evaluations.

RESULTS

Dust exposure induced NAFLD features in rats. It increased the serum levels of liver enzymes, LDL, TG, cholesterol, MDA, and mRNA expression of NFκβ, TNFα, IL-6, HO1, and miRs [122 and 34a], while decreasing serum levels of HDL and liver TAC. Treatment with GA improved liver enzymes, serum levels of miRs, TG, expression of NFκβ, TNFα, IL-6, Nrf2, and HO1 and liver MDA and TAC levels, while it could not improve HDL, LDL, and cholesterol.

CONCLUSION

This study showed dust exposure induced NAFLD in Wistar rats through inducing oxidative stress. Oxidative stress through activating the inflammatory pathways caused NAFLD features. Gallic acid treatment by inhibiting oxidative stress effectively protected liver function against dust induced inflammation.

摘要

目的

与环境污染相关的疾病负担和死亡正成为一项重大的公共卫生挑战,尤其是在发展中国家。本研究旨在调查粉尘暴露对大鼠肝功能及其结构的影响。还使用没食子酸(GA)作为一种有效的抗氧化剂来治疗暴露于粉尘的大鼠的非酒精性脂肪性肝病(NAFLD)。

材料与方法

将24只大鼠随机分为3组:对照组(CA)、粉尘+生理盐水组(停止粉尘暴露后,大鼠口服1 ml生理盐水作为赋形剂,连续14天)和粉尘+GA组(停止粉尘暴露后,大鼠口服100 mg/kg GA,连续14天)。大鼠隔天暴露于CA/粉尘6周。实验结束时,将大鼠麻醉,采集其血液样本和肝脏切片以进行分子、生物医学和组织病理学评估。

结果

粉尘暴露诱导大鼠出现NAFLD特征。它增加了肝酶、低密度脂蛋白(LDL)、甘油三酯(TG)、胆固醇、丙二醛(MDA)的血清水平,以及核因子κB(NFκβ)、肿瘤坏死因子α(TNFα)、白细胞介素-6(IL-6)、血红素加氧酶1(HO1)和微小RNA(miRs)[122和34a]的mRNA表达,同时降低了高密度脂蛋白(HDL)的血清水平和肝脏总抗氧化能力(TAC)。用GA治疗可改善肝酶、miRs的血清水平、TG、NFκβ、TNFα、IL-6、核因子E2相关因子2(Nrf2)和HO1的表达以及肝脏MDA和TAC水平,但不能改善HDL、LDL和胆固醇。

结论

本研究表明,粉尘暴露通过诱导氧化应激在Wistar大鼠中诱发NAFLD。氧化应激通过激活炎症途径导致NAFLD特征。没食子酸通过抑制氧化应激有效地保护肝功能免受粉尘诱导的炎症影响。

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