Nrf2 attenuates methamphetamine-induced myocardial injury by regulating oxidative stress and apoptosis in mice

Author:

Yu Hao12ORCID,Peng Yanxia1ORCID,Dong Wenjuan1,Shen Baoyu1,Yang Genmeng1,Nie Qianyun1,Tian Yan1,Qin Lixiang1,Song Chunhui1,Chen Bingzheng1,Zhao Yongna3,Li Lihua1,Hong Shijun1ORCID

Affiliation:

1. NHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, China

2. West China Hospital, Sichuan University, Chengdu, China

3. Key Laboratory of Natural Medicine Pharmacology of Yunnan Province, Kunming Medical University, Kunming, China

Abstract

Objectives Methamphetamine (MA) abuse is a serious social problem worldwide. Cardiovascular complications were the second leading cause of death among MA abusers. We aimed to clarify the effects of MA on myocardial injury, oxidative stress, and apoptosis in myocardial cells and to explore the potential mechanism of nuclear factor-erythroid factor 2-related factor 2 (Nrf2) in MA-induced oxidative stress and apoptosis. Methods An acute cardiac toxicity model of MA was established by intraperitoneal injection of MA (2 mg/kg) for 5 days. Nrf2 activation (by sulforaphane (SFN) 1 h before MA injection) and Nrf2 gene knockout were performed to explore the regulatory effects of Nrf2 on cardiac toxicity. Results The protein expressions of Nrf2 ( p < .001) and heme oxygenase-1 (HO-1) were increased ( p < .01), suggesting that MA activated the Nrf2/HO-1 pathway. In the MA group, cardiac injury score ( p < .001) and cardiac troponin I (cTnI) protein expression increased ( p < .01). Malondialdehyde (MDA) content increased ( p < .001), superoxide dismutase (SOD) activity decreased ( p < .05). Protein expressions of Caspase-3 ( p < .001) and Bax ( p < .001) increased, and Bcl-2 decreased ( p < .001) as well. These changes were reversed by activation of Nrf2 but became more pronounced after Nrf2 knockout, suggested that the activation and knockout of Nrf2 attenuated and aggravated MA-induced myocardial injury, oxidative stress and apoptosis in myocardial cells, respectively. Conclusions MA administration induced myocardial injury, oxidative stress, and apoptosis in mice. Nrf2 attenuated MA-induced myocardial injury by regulating oxidative stress and apoptosis, thus playing a protective role.

Funder

Joint Research Project of Science and Technology Department of Yunnan Province & Kunming Medical University

National Natural Science Foundation of China

Yunnan Provincial Engineering Research Center of Forensic Medicine; Research Project of NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University

Graduate Innovation Fundation of Kunming Medical University

Publisher

SAGE Publications

Subject

Health, Toxicology and Mutagenesis,Toxicology,General Medicine

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3