Publication Date:
2015-05-01
Description:
Objective : We previously reported that S-propargyl-cysteine (SPRC) exerts cardioprotective effects by elevating H 2 S levels via the CSE/H 2 S pathway. In this study, we investigated the cardioprotective effects and pharmacokinetic properties of a controlled release formulation of S-propargyl-cysteine (CR-SPRC) in an in vivo ratmodel of myocardial infarction (MI). Methods: Rats were randomly assigned to seven groups that were pre-treated with CR-SPRC daily for 7 days prior to ligation of the left anterior descending coronary artery to induce MI. Cardiac function and infarct size were determined after MI, and we examined the activity of antioxidant enzymes, expression of anti-inflammation proteins, and hydrogen sulfide levels. Mixed-mode, reversed-phase and cation-exchange HPLC–MS/MS were used to compare the pharmacokinetic properties of CR-SPRC and SPRC. Results :CR-SPRC significantly reduced infarct size and CK and LDH leakage, and it preserved cardiac function during MI. CR-SPRC displayed antioxidant properties, preserving GSH, CAT and SOD levels while reducing MDA levels. Moreover, CR-SPRC significantly reduced the protein levels of inflammatory biomarkers (phospho-NF-κB p65/NF-κB p65, TNF-α) and increased cystathionine-γ-lyase (CSE) and Iκ-Bα protein levels. CR-SPRC had better pharmacokinetic properties than SPRC, with a reduced concentration peak (C max ), prolonged time to reach peak concentration (T max ), prolonged mean residence time (MRT inf ) and increased AUC 0- t . Conclusions : CR-SPRC showed protective effects against MI via the CSE/H 2 S pathway and demonstrated better cardioprotective effects than SPRC by prolonging the release of endogenous H 2 S.
Print ISSN:
0144-8463
Electronic ISSN:
1573-4935
Topics:
Biology
,
Chemistry and Pharmacology
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