N-acetylcysteine ameliorates monocrotophos exposure-induced mitochondrial dysfunctions in rat liver

IF 2.8 4区医学 Q2 TOXICOLOGY

Toxicology Mechanisms and Methods Pub Date : 2022-04-11 DOI:10.1080/15376516.2022.2064258

Jagjeet Singh, Annu Phogat, Vijay Kumar, Vinay Malik

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引用次数: 5

Abstract

Abstract Background: Monocrotophos (MCP) is an organophosphate pesticide with well-known toxicity in mammals. Exposure of MCP is associated with altered molecular physiology at sub-cellular levels. This study investigated the efficacy of N-acetylcysteine (NAC) against MCP exposure mediated mitochondrial dysfunctions in hepatic tissue of rats. Methods: Male Wistar rats were given NAC (200 mg/kg b.wt), MCP (0.9 mg/kg b.wt) and NAC together with MCP, intragastrically for 28 consecutive days. Mitochondrial complexes activities were evaluated using biochemical analysis. mRNA expression of mitochondrial complexes subunits, PGC-1α and its downstream regulators were analyzed using polymerase chain reaction. Results: Exposure of MCP (0.9 mg/kg b.wt, intragastrically, 28 d) decreased mitochondrial complexes activities and gene expression of complexes subunits. The expression of PGC-1α, NRF-1, NRF-2, and Tfam was also reduced significantly. The administration of NAC (200 mg/kg b.wt, intragastrically, 28 d) significantly increased mitochondrial complexes activities and gene expression of complexes subunits. Additionally, NAC also maintained mitochondrial functions, and enhanced the gene expression of PGC-1α and its downstream regulators. Conclusion: The results of this study indicate that NAC prevents hepatic mitochondrial dysfunctions and maintains PGC-1α signaling. In conclusion, NAC might be speculated as a therapeutic agent for mitochondrial dysfunctions following toxic exposures.

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n -乙酰半胱氨酸改善单氯磷暴露诱导的大鼠肝脏线粒体功能障碍

摘要背景:单效磷(MCP)是一种对哺乳动物具有毒性的有机磷农药。MCP暴露与亚细胞水平的分子生理改变有关。本研究探讨了n -乙酰半胱氨酸(NAC)对MCP暴露介导的大鼠肝组织线粒体功能障碍的影响。方法:雄性Wistar大鼠灌胃NAC (200 mg/kg b.wt)、MCP (0.9 mg/kg b.wt)及NAC与MCP联合灌胃，连续28 d。采用生化分析评价线粒体复合物活性。采用聚合酶链反应分析线粒体复合物亚基、PGC-1α及其下游调节因子的mRNA表达。结果:暴露于MCP (0.9 mg/kg b.wt，灌胃，28 d)降低线粒体复合物活性和复合物亚基的基因表达。PGC-1α、NRF-1、NRF-2和Tfam的表达也显著降低。NAC (200mg /kg b.wt，灌胃，28 d)显著增加线粒体复合物活性和复合物亚基的基因表达。此外，NAC还能维持线粒体功能，增强PGC-1α及其下游调控因子的基因表达。结论:NAC可预防肝线粒体功能障碍，维持PGC-1α信号通路。总之，NAC可能被推测为毒性暴露后线粒体功能障碍的治疗剂。

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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.