Article Publish Status: FREE
Abstract Title:

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

Abstract Source:

Hum Exp Toxicol. 2023 ;42:9603271231219488. PMID: 38031934

Abstract Author(s):

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

Article Affiliation:

Hao Yu


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) andgene knockout were performed to explore the regulatory effects of Nrf2 on cardiac toxicity.

RESULTS: The protein expressions of Nrf2 (<.001) and heme oxygenase-1 (HO-1) were increased (<.01), suggesting that MA activated the Nrf2/HO-1 pathway. In the MA group, cardiac injury score (<.001) and cardiac troponin I (cTnI) protein expression increased (<.01). Malondialdehyde (MDA) content increased (<.001), superoxide dismutase (SOD) activity decreased (<.05). Protein expressions of Caspase-3 (<.001) and Bax (<.001) increased, and Bcl-2 decreased (<.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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Sayer Ji
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