4.6 Article

Reperfusion-induced injury and the effects of the dithioacetate type hydrogen sulfide donor ibuprofen derivative, BM-88, in isolated rat hearts

Journal

Publisher

ELSEVIER
DOI: 10.1016/j.ejps.2023.106449

Keywords

H 2 S-donor; Heart; Ischemia/reperfusion; Arrhythmias; Cell death

Ask authors/readers for more resources

This study aimed to synthesize a newly designed H2S-releasing ibuprofen derivative, BM-88, and investigate its pharmacological characterization in isolated rat hearts. In vitro experiments showed that preadministration of 10μM BM-88 significantly reduced the incidence of reperfusion-induced ventricular fibrillation (VF), but there was no clear dose dependent reduction. Furthermore, 10μM BM-88 provided substantial protection and reduced the infarct size in the ischemic/reperfused myocardium, without significant changes in coronary flow and heart rates.
Hydrogen sulfide (H2S) plays an important role in cardiac protection by regulating various redox signalings associated with myocardial ischemia/reperfusion (I/R) induced injury. The goal of the present investigations is the synthesis of a newly designed H2S-releasing ibuprofen derivative, BM-88, and its pharmacological characterization regarding the cardioprotective effects in isolated rat hearts. Cytotoxicity of BM-88 was also estimated in H9c2 cells. H2S-release was measured by an H2S sensor from the coronary perfusate. Increasing concentrations of BM-88 (1.0 to 20.0 & mu;M) were tested in vitro studies. Preadministration of 10 & mu;M BM-88 significantly reduced the incidence of reperfusion-induced ventricular fibrillation (VF) from its drug-free control value of 92% to 12%. However, no clear dose dependent reduction in the incidence of reperfusion-induced VF was observed while different concentrations of BM-88 were used. It was also found that 10 & mu;M BM-88 provided a substantial protection and significantly reduced the infarct size in the ischemic/reperfused myocardium. However, this cardiac protection was not reflected in any significant changes in coronary flow and heart rates. The results support the fact that H2S release plays an important role mitigating reperfusion-induced cardiac damage.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available