%0 Journal Article
%T Ciprofol Mitigates Myocardial Ischemia/Reperfusion Injury by Suppressing Ferroptosis via HIF-1α Upregulation
%A Evelyn Mitchell
%A Caleb Parker
%J Pharmaceutical Sciences and Drug Design
%@ 3062-4428
%D 2023
%V 3
%N 1
%R 10.51847/5zXXEoIBES
%P 138-156
%X Ciprofol, a recently developed intravenous anesthetic, is increasingly utilized in anesthesia and sedation. While prior research has shown its potential to alleviate cerebral ischemia/reperfusion (I/R) injury by reducing oxidative stress and inflammation, its cardioprotective effects and underlying mechanisms remain unexplored. This study investigated whether ciprofol mitigates myocardial I/R injury by modulating ferroptosis. Myocardial I/R injury was induced in mice by 30 minutes of ischemia followed by 24 hours of reperfusion, and hypoxia/reoxygenation (H/R) injury was modeled in H9c2 cardiomyocytes with 6 hours of hypoxia and 6 hours of reoxygenation. Ciprofol was administered prior to ischemia or hypoxia. Assessments included echocardiography, TTC and HE staining, DAB-enhanced Perl’s staining, transmission electron microscopy, and various assays for oxidative stress, mitochondrial function, and ferroptosis (FerroOrange, Liperfluo, JC-1, Rhodamine-123, DCFH-DA, Western blot). Cell viability, serum cardiac enzymes, and ferroptosis-related biomarkers were measured. HIF-1α was specifically targeted using siRNA and the inhibitor BAY87-2243 to explore the mechanistic basis.Administration of ciprofol markedly decreased infarct size and myocardial injury, reduced oxidative stress and mitochondrial damage, inhibited Fe²⁺ accumulation and ferroptosis, and improved cardiac performance in I/R-injured mice. Similarly, in H/R-treated cardiomyocytes, ciprofol enhanced cell survival, prevented mitochondrial dysfunction, and lowered intracellular Fe²⁺ and lipid peroxidation. Mechanistic studies revealed that ciprofol increased HIF-1α and GPX4 expression while suppressing ACSL4. The protective effects were reversed upon HIF-1α knockdown or inhibition, confirming its central role in ciprofol-mediated cardioprotection. Ciprofol exerts cardioprotective effects in myocardial I/R and H/R injury primarily by limiting ferroptosis through HIF-1α upregulation.
%U https://galaxypub.co/article/ciprofol-mitigates-myocardial-ischemiareperfusion-injury-by-suppressing-ferroptosis-via-hif-1a-upre-09urrjszbvgzyrs