<p>A Novel Liposomal S-Propargyl-Cysteine: A Sustained Release of Hydrogen Sulfide Reducing Myocardial Fibrosis via TGF-β1/Smad Pathway</p>

Abstract

S-propargyl-cysteine (SPRC; alternatively known as ZYZ-802) is a novel modulator of endogenous tissue H 2 S concentrations with known cardioprotective and antiinflammatory effects. However, its rapid metabolism and excretion have limited its clinical application. To overcome these issues, we have developed some novel liposomal carriers to deliver ZYZ-802 to cells and tissues and have characterized their physicochemical, morphological and pharmacological properties. Methods: Two liposomal formulations of ZYZ-802 were prepared by thin-layer hydration and the morphological characteristics of each liposome system were assessed using a laser particle size analyzer and transmission electron microscopy. The entrapment efficiency and ZYZ-802 release profiles were determined following ultrafiltration centrifugation, dialysis tube and HPLC measurements. LC-MS/MS was used to evaluate the pharmacokinetic parameters and tissue distribution profiles of each formulation via the measurements of plasma and tissues ZYZ-802 and H 2 S concentrations. Using an in vivo model of heart failure (HF), the cardio-protective effects of liposomal carrier were determined by echocardiography, histopathology, Western blot and the assessment of antioxidant and myocardial fibrosis markers. Results: Both liposomal formulations improved ZYZ-802 pharmacokinetics and optimized H 2 S concentrations in plasma and tissues. Liposomal ZYZ-802 showed enhanced cardioprotective effects in vivo. Importantly, liposomal ZYZ-802 could inhibit myocardial fibrosis via the inhibition of the TGF-β1/Smad signaling pathway. Conclusion: The liposomal formulations of ZYZ-802 have enhanced pharmacokinetic and pharmacological properties in vivo. This work is the first report to describe the development of liposomal formulations to improve the sustained release of H 2 S within tissues.

Hydrogen sulfide releasing molecule MZe786 inhibits soluble Flt-1 and prevents preeclampsia in a refined RUPP mouse model

“…Performing the surgery at E11.5 also gives a good ‘therapeutic window’. The protective effect of H 2 S has been widely reported in cardiovascular [ [38] , [39] , [40] , [41] ], neurodegenerative diseases [ 42 , 43 ] and in multiple cancer pathophysiology [ [44] , [45] , [46] ]. In this study, we used MZe786, which is a H 2 S releasing aspirin as a source of H 2 S. Chronic use of aspirin is frequently associated with gastropathy, partly due to, redox imbalances [ 47 ].…”

Pivotal Role of TGF-β/Smad Signaling in Cardiac Fibrosis: Non-coding RNAs as Effectual Players

“…Evidence corroborates the existence of cross-regulation between the two ncRNAs mediated fibrosis-stimulating pathways and its role in cardiac fibrosis pathophysiology. Recognizing mechanisms associated with such cross-regulation provides possibilities for the development of new therapeutic approaches to reverse cardiac fibrosis ( 10 – 12 ). The present review examines TGF-β, as well as Smad signaling, followed by their contribution in the cardiac fibrosis pathogenesis.…”

The Preparation of a Novel Poly(Lactic Acid)-Based Sustained H2S Releasing Microsphere for Rheumatoid Arthritis Alleviation

“…The SPRC has been reported to be able to promote the H 2 S release in vivo through the CSE/H 2 S signaling pathway, according to our previous studies [ 6 , 7 ], and the CSE mainly distributed in heart and liver [ 48 , 49 , 50 , 51 ]. The expression of CSE in the heart and liver were investigated and the increased expression could be found in both SPRC and SPRC@PLA groups.…”