DOI: 10.1177/09603271231219488 ISSN: 0960-3271

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

Hao Yu, Yanxia Peng, Wenjuan Dong, Baoyu Shen, Genmeng Yang, Qianyun Nie, Yan Tian, Lixiang Qin, Chunhui Song, Bingzheng Chen, Yongna Zhao, Lihua Li, Shijun Hong
  • Health, Toxicology and Mutagenesis
  • Toxicology
  • General Medicine

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.

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