Cardioprotective Effects of a Novel Hydrogen Sulfide Agent–Controlled Release Formulation of S-Propargyl-Cysteine on Heart Failure Rats and Molecular Mechanisms

Chengrong Huang,Xu Liu,Fenfen Ma,Juntao Kan,Yi Zhun Zhu,Yunzeng Zou,Shujun Wang,Ba Hieu Tran,Yu Huang

doi:10.1371/journal.pone.0069205

Chengrong Huang, Xu Liu + Show 7 more

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https://doi.org/10.1371/journal.pone.0069205

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Abstract

ObjectiveHeart failure (HF) is one of the most serious diseases worldwide. S-propargyl-cysteine (SPRC), a novel modulator of endogenous hydrogen sulfide, is proved to be able to protect against acute myocardial ischemia. In order to produce more stable and sustainable hydrogen sulfide, we used controlled release formulation of SPRC (CR-SPRC) to elucidate possible cardioprotective effects on HF rats and investigate involved mechanisms on apoptosis and oxidation.MethodsLeft coronary artery was occluded to induce HF model of rat. The survival rats were randomly divided into 7 groups after 24 hours and treated with drugs for 6 weeks. Echocardiographic indexes were recorded to determine cardiac function. TTC staining was performed to determine infarct size. Plasmatic level of hydrogen sulfide was detected by modified sulfide electrode. Activity of enzyme and expression of protein were determined by colorimetry and Western blot, respectively.ResultsThe cardioprotective effects of CR-SPRC on HF rats were confirmed by significant reduction of infarct size and improvement of cardiac function, with better effects compared to normal SPRC. CR-SPRC modulated antioxidant defenses by preserving levels of GSH, CAT and SOD and reducing CK leakage. In addition, CR-SPRC elevated ratio of Bcl-2/Bax and inhibited activity of caspases to protect against myocardial apoptosis. The cardioprotective effects of CR-SPRC were mediated by hydrogen sulfide.ConclusionsAll experiment data indicated cardioprotective effects of CR-SPRC on HF rats. More importantly, CR-SPRC exerted better effects than normal SPRC in all respects, providing a new perspective on hydrogen sulfide-mediated drug therapy.

Highlights

Heart failure (HF) is a condition in which the heart can no longer pump sufficient blood to meet the need of the body [1]
We proved SPRC and two other cysteine analogues could protect against acute myocardial ischemia by reducing the deleterious effects of oxidative stress through modulating the endogenous hydrogen sulfide [13]
controlled release formulation of SPRC (CR-SPRC) Improved Survival of HF Rats Unlike normal SPRC, CR-SPRC did not slow down the growth of body weight of HF rats compared with that in sham group (Figure 1A)

Summary

Introduction

Heart failure (HF) is a condition in which the heart can no longer pump sufficient blood to meet the need of the body [1]. More than 23 million people around the world are suffering from this disease, causing it to be the most serious health issue in both developed and developing countries. Many factors such as ischemic heart disease, hypertension, diabetes, dyslipidemia and smoking can increase the risk for development of HF [2]. Besides as an acknowledged KATP opener [7], hydrogen sulfide has been proved to play many roles in protecting against cardiovascular diseases such as hypertension [8], atherosclerosis [9], acute myocardial ischemia [10,11] and chronic heart failure [12]

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