title: Cardioprotective effects of a novel hydrogen sulfide agent-controlled release formulation of S-propargyl-cysteine on heart failure rats and molecular mechanisms.
abstract: OBJECTIVE
  Heart 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.
  
  
  METHODS
  Left 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  All 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.
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, Shanghai, China.
authors.forename: Chengrong
authors.initials: C
authors.lastname: Huang
authors.forename: Juntao
authors.initials: J
authors.lastname: Kan
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.forename: Fenfen
authors.initials: F
authors.lastname: Ma
authors.forename: Ba Hieu
authors.initials: BH
authors.lastname: Tran
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.forename: Shujun
authors.initials: S
authors.lastname: Wang
authors.forename: Yi Zhun
authors.initials: YZ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003545:Cysteine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D005355:Fibrosis; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006862:Hydrogen Sulfide / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018384:Oxidative Stress; D051381:Rats
chemical_list: D002316:Cardiotonic Agents; D003692:Delayed-Action Preparations; C556437:S-propargylcysteine; D003545:Cysteine; D006862:Hydrogen Sulfide