EP04 Therapeutic modulators of endogenous H2S synthesis: Bench to bedside

Abstract

The release of endogenous H2S from cells is likely to occur in lesser amounts and at a much slower rate than that from sulfide salts, which could not mimic the biological effects of naturally produced H2S. Therefore, modulation of endogenous H2S production may be of therapeutic benefit in cardiovascular and CNS diseases. A significant amount of effort is being channeled into developing novel therapeutics based on delivering H2S. We have identified that the salubrious effects of H2S may due to its various biological activities, such as anti-oxidation, anti-inflammation etc. Interestingly, our group also found that S-propargyl-cysteine (SPRC), a novel sulfur-containing amino acid, exerted neuroprotective and cardiovascular-protective effects in in vivo and in vitro studies through modulation of endogenous cystathionine γ-lyase (CSE)/H2S system. For example, we identified that SPRC or control-released-preparation of SPRC was shown to preserve endogenous CSE/H2S levels and upregulated various anti-oxidative enzymes after myocardial infarction. In addition, SPRC also prevent against cytokine-mediated endothelial dysfunction. Furthermore, SPRC may attenuate inflammatory responses and spatial learning and memory impairment in bilateral intracerebroventricular LPS-injected rats, atleast partly, by H2S-mediated pathway. Based on the above studies, SPRC has been already in the final stage of pre-clinical studies. Taken together, these data suggest that SPRC, a novel endogenous H2S-modulated agent, can be used as a neuroprotective and cardiovascular-protective agent for potential clinical trials.