Ferroptosis is an
iron-dependent regulated
necrosis. This study aims to evaluate the contribution of ferroptosis to
ischemia or
reperfusion injury, and lay a basis for precise
therapy of
myocardial infarction. The Sprague-Dawley (SD) rat hearts were subjected to
ischemia for different duration or the hearts were treated with 1 h-ischemia plus different duration of reperfusion. The myocardial injury was assessed by biochemical assays and
hematoxylin &
eosin (HE) staining. The ferroptosis was evaluated with the levels of
acyl-CoA synthetase long-chain family member 4 (ACSL4),
glutathione peroxidase 4 (GPX4),
iron, and
malondialdehyde.
Iron chelator (
deferoxamine) was applied to verify the contribution of ferroptosis to
ischemia and
reperfusion injury. The results showed that ischemic injury (
infarction and CK release) was getting worse with the extension of
ischemia, but no significant changes in ferroptosis indexes (ACSL4, GPX4,
iron, and
malondialdehyde) in cardiac tissues were observed. Differently, the levels of ACSL4,
iron, and
malondialdehyde were gradually elevated with the extension of reperfusion concomitant with a decrease of GPX4 level. In the
ischemia-treated rat hearts, no significant changes in myocardial injury were observed in the presence of
deferoxamine, while in the
ischemia/reperfusion-treated rat hearts, myocardial injury was markedly attenuated in the presence of
deferoxamine concomitant with a reduction of ferroptosis. Based on these observations, we conclude that ferroptosis occurs mainly in the phase of myocardial reperfusion but not
ischemia. Thus, intervention of ferroptosis exerts beneficial effects on
reperfusion injury but not ischemic injury, laying a basis for precise
therapy for patients with
myocardial infarction.