Hydrogen sulfide: anti-inflammatory and cytoprotective effects

Introduction

Pharmacological actions of gaseous biological mediator hydrogen sulfide (H₂S) include vasodilatation, inhibition of mitochondrial respiration as well as induction of suspended animation-like state [1, 2]. Its beneficial cellular actions include cytoprotection and anti-inflammatory effects [2].

Methods

Rodent models of ischemia and reperfusion of the heart, murine and ovine models of acute respiratory distress syndrome, a canine model of cardiopulmonary bypass, porcine models of myocardial infarction and thoracoabdominal aortic aneurysm surgery were used. H₂S was administered in an iso-osmolar, pH-neutral intravenous formulation (IK-1001).

Results

In a mouse model of myocardial infarction, a significant protection by IK-1001 was seen in terms of reduction of myocardial infarct size. These effects were accompanied by reduction in myocardial IL-1 levels and reduction in neutrophil infiltration [3]. The cardiac protection of H₂S was confirmed in a porcine model of myocardial ischemia [4] and in a canine model of cardiopulmonary bypass surgery. IK-1001 was also protective in murine and ovine models of acute respiratory distress syndrome, where improvement in survival and pulmonary function was accompanied by a reduction in oxidant stress and suppression of the production of IL-6 and inhibition of the expression of inducible nitric oxide synthase [5]. In models of thoracoabdominal aneurysm surgery, reperfusion was accompanied with significant increases in the production of IL-1 and IL-6, which were reduced by IK-1001. IK-1001 also improved renal function, provided hemodynamic stabilization and attenuated oxidative DNA damage [6].

Conclusion

H₂S thus exerts organ-protective and anti-inflammatory effects in various animal models of critical illness. The mechanisms may involve metabolic effects leading to the induction of hypothermia, antioxidant mechanisms, modulation of gene expression, activation of KATP channels, and inhibition of inflammatory cell activation.