Session Speaker
The
Therapeutic Potential of Hydrogen Sulfide
Csaba Szabo
USA
Hydrogen sulfide (H2S) is one of
the three principal endogenous gaseotransmitters, which is increasingly
recognized as an important signaling molecule in the cardiovascular
system. The production of H2S from
L-cysteine is catalyzed by cystathione-gamma-lyase (CSE) and cystathione-beta-synthetase
(CBS). The effects of H2S include
vasodilatation, inhibition of neutrophil adhesion, as well as antioxidant
and cytoprotective actions. H2S can
induce a reversible state of hypothermia and a suspended animation-like
state in rodents, and can protect rodents from lethal hypoxia and
lethal hemorrhage. H2S also exerts
significant protective effects in myocardial, hepatic and renal reperfusion
injury. In recent years, multiple approaches have been identified
for the therapeutic exploitation of H2S,
based on the parenteral administration of various formulations of
the molecule or its prodrugs. Furthermore, the addition of sulfide-releasing
moieties to generic anti-inflammatory drugs can enhance the therapeutic
effect of the parent compound, as validated in rodent models of inflammatory
bowel disease, systemic inflammation and pain. Several sulfide-based
experimental therapeutics are advancing in preclinical stages of drug
development. A parenteral formulation of H2S
(IK-1001, sodium sulfide for injection) has entered clinical trials.
In the current lecture we overview some of the recent advances on
the biology, medicinal chemistry and potential therapeutic uses of
H2S and its prodrugs.
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