Emerging pharmacological tools to control hydrogen sulfide signaling in critical illness.

Hydrogen sulfide (HS) has long been known as a toxic environmental hazard. Discovery of physiological roles of HS as a neurotransmitter by Kimura and colleagues triggered an intensive research in the biological roles of HS in the past decades. Manipulation of HS levels by inhibiting HS synthesis or administration of HS-releasing molecules revealed beneficial as well as harmful effects of HS. As a result, it is now established that HS levels are tightly controlled and too much or too little HS levels cause harm. Nonetheless, translation of sulfide-based therapy to clinical practice has been stymied due to the very low therapeutic index of sulfide and the incomplete understanding of endogenous sulfide metabolism. One potential strategy to circumvent this problem is to use a safe and stable sulfide metabolite that may mediate effects of HS. Alternatively, endogenous sulfide levels may be controlled using specific sulfide scavengers. In this review article, the role of endogenous HS production and catabolism will be briefly reviewed followed by an introduction of thiosulfate and HS scavengers as novel pharmacological tools to control HS-dependent signaling.