Rotenone induces hepatotoxicity in rats by activating the mitochondrial pathway of apoptosis

IF 2.8 4区医学 Q2 TOXICOLOGY

Toxicology Mechanisms and Methods Pub Date : 2022-03-06 DOI:10.1080/15376516.2022.2049940

Huan Wang, Yinzhu Jin, Yao Wang, Xue-wei Wang, Wenhui Yu, Xiaowen Jiang

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引用次数: 3

Abstract

Abstract As a pesticide extracted from plants, rotenone is widely used to control plant pests. In order to explore the safety of rotenone in the environment, we took 60 healthy male SD rats and randomly divided them into rotenone low-dose group, rotenone medium-dose group, rotenone high-dose group, dimethyl sulfoxide group (DMSO), and control group. After 28 days of oral administration, the rat liver tissue ultrastructure, liver function, oxidative stress indexs, mitochondrial function, and apoptosis-related factors were tested to evaluate the hepatotoxicity and toxicological mechanism of rotenone. The results showed that rotenone significantly increased the hepatic index of rats and the activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum. Rotenone can reduce the number of endoplasmic reticulum of hepatocyte, concentrate chromatin and make the hepatocyte nuclears irregular. Rotenone weakened the ATP synthesis ability in mitochondria, decreased the activity of ATP enzyme in mitochondria, and increased the mitochondrial membrane potential in the high-dose group. And it induced oxidative stress damage to the mitochondria of rat liver cells. Rotenone can upregulate the expression of pro-apoptotic factors and downregulate the expression of anti-apoptotic factors. These results indicate that oral rotenone in rats induced hepatotoxicity in a dose-dependent manner. The mechanism of rotenone poisoning is that oxidative stress damages organelles of hepatocyte such as mitochondria and endoplasmic reticulum, resulting in their function being weakened or lost, leading to hepatocyte apoptosis.

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鱼藤酮通过激活线粒体凋亡途径诱导大鼠肝毒性

摘要鱼藤酮作为一种从植物中提取的农药，被广泛用于防治植物害虫。为了探讨鱼藤酮在环境中的安全性，我们选取60只健康雄性SD大鼠，将其随机分为鱼藤酮低剂量组、鱼藤酮中剂量组、高剂量组、二甲基亚砜组和对照组。28之后通过对大鼠肝组织超微结构、肝功能、氧化应激指数、线粒体功能和细胞凋亡相关因素的检测，评价鱼藤酮的肝毒性和毒理学机制。结果表明，鱼藤酮能显著提高大鼠的肝脏指数和血清天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）的活性。鱼藤酮可以减少肝细胞内质网的数量，浓缩染色质，使肝细胞核酸不规则。鱼藤酮在高剂量组中削弱了线粒体中的ATP合成能力，降低了线粒体中ATP酶的活性，并增加了线粒体膜电位。并诱导大鼠肝细胞线粒体氧化应激损伤。鱼藤酮可上调促细胞凋亡因子的表达，下调抗细胞凋亡因子表达。这些结果表明，大鼠口服鱼藤酮以剂量依赖的方式诱导肝毒性。鱼藤酮中毒的机制是氧化应激损伤肝细胞的线粒体和内质网等细胞器，导致其功能减弱或丧失，导致肝细胞凋亡。

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来源期刊

Toxicology Mechanisms and Methods TOXICOLOGY-

自引率

3.10%

发文量

期刊介绍： Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment. A variety of research methods are discussed, including: In vivo studies with standard and alternative species In vitro studies and alternative methodologies Molecular, biochemical, and cellular techniques Pharmacokinetics and pharmacodynamics Mathematical modeling and computer programs Forensic analyses Risk assessment Data collection and analysis.