• Shock · Sep 2021

    Etomidate Attenuates the Ferroptosis in Myocardial Ischemia/Reperfusion Rat Model Via Nrf2 Pathway.

    • Zhenqian Lv, Feng'e Wang, Xingfeng Zhang, Xiting Zhang, Jing Zhang, and Ran Liu.
    • Department of Cardiac Surgery, Qingdao Fuwai Cardiovascular Hospital, Qingdao, China.
    • Shock. 2021 Sep 1; 56 (3): 440-449.

    BackgroundFerroptosis has been found to play an important role in myocardial ischemia reperfusion (MIR) injury (MIRI). This study aimed to explore whether the improvement effect of Etomidate (Eto) on MIRI was related to ferroptosis.MethodsThe MIRI rats were constructed using left anterior descending artery occlusion for 30 min followed by reperfusion for 3 h. The Eto post-conditioning was performed by Eto administration at the beginning of the reperfusion. For rescue experiments, MIRI rats were pretreated with ferroptosis inducer erastin or Nrf2 inhibitor ML385 intraperitoneally 1 h prior to MIR surgery.ResultsEto mitigated cardiac dysfunction and myocardium damage, as well as the release of creatine kinase and lactate dehydrogenase caused by ischemia/reperfusion (IR). Additionally, Eto reduced the expression of myocardial fibrosis-related proteins (collagen II and α-smooth muscle actin) and the secretion of inflammatory factors (IL-6, IL-1β, and TNF-α) in MIRI rats. Also, Eto inhibited IR-induced ferroptosis in myocardium, including reducing superoxide dismutase content, glutathione activity, and glutathione peroxidase 4 expression, while increasing the levels of malondialdehyde and iron and Acyl-CoA synthetase long-chain family member 4. Moreover, the inhibition of Eto on IR-induced myocardial fibrosis and inflammation could be eliminated by erastin. The up-regulation of Nrf2 and HO-1 protein expression, and the nuclear translocation of Nrf2 induced by Eto in the myocardial tissues of MIRI rats, could be prevented by erastin. Besides, ML385 eliminated the inhibition of Eto on ferroptosis induced by MIR.ConclusionsEto attenuated the myocardial injury by inhibiting IR-induced ferroptosis via Nrf2 pathway, which may provide a new idea for clinical reperfusion therapy.Copyright © 2021 by the Shock Society.

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