Related Experiment Video
Updated: Nov 3, 2025
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
Etomidate Attenuates the Ferroptosis in Myocardial Ischemia/Reperfusion Rat Model via Nrf2/HO-1 Pathway
Zhenqian Lv1, Feng'e Wang2, Xingfeng Zhang3
1Department of Cardiac Surgery, Qingdao Fuwai Cardiovascular Hospital, Qingdao, China.
Background:
Ferroptosis 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.
Methods:
The 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.
Results:
Eto 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.
Conclusions:
Eto attenuated the myocardial injury by inhibiting IR-induced ferroptosis via Nrf2 pathway, which may provide a new idea for clinical reperfusion therapy.
Insights
Etomidate (Eto) protects against myocardial ischemia reperfusion injury by inhibiting ferroptosis. This effect is mediated through the Nrf2 pathway, offering a novel therapeutic approach for reperfusion injury.
Area of Science:
- Cardiology
- Cellular Biology
- Pharmacology
Background:
- Myocardial ischemia reperfusion injury (MIRI) is a significant clinical concern.
- Ferroptosis, a regulated form of cell death, plays a critical role in MIRI pathogenesis.
- Etomidate (Eto) has shown potential in mitigating MIRI, but its underlying mechanisms require elucidation.
Purpose of the Study:
- To investigate whether Etomidate's protective effects against MIRI are linked to the inhibition of ferroptosis.
- To explore the role of the Nrf2 pathway in Etomidate's action on MIRI.
Main Methods:
- Myocardial ischemia reperfusion (MIRI) rat model established via left anterior descending artery occlusion and reperfusion.
- Etomidate post-conditioning administered at reperfusion onset.
- Rescue experiments involved pretreatment with erastin (ferroptosis inducer) or ML385 (Nrf2 inhibitor).
Main Results:
- Etomidate mitigated cardiac dysfunction, myocardial damage, and release of cardiac enzymes (creatine kinase, lactate dehydrogenase).
- Etomidate reduced myocardial fibrosis markers and inflammatory factors (IL-6, IL-1β, TNF-α).
- Etomidate inhibited ferroptosis by modulating markers of oxidative stress, lipid peroxidation, and iron accumulation, and influenced Nrf2/HO-1 pathway activation. Erastin reversed Etomidate's protective effects, while ML385 blocked Etomidate's inhibition of ferroptosis.
Conclusions:
- Etomidate attenuates myocardial injury in MIRI by inhibiting ferroptosis through the Nrf2 pathway.
- This study provides a novel therapeutic strategy for clinical reperfusion therapy.
- Targeting ferroptosis via Etomidate offers a promising avenue for managing MIRI.
