Hydrogen sulfide (H2S) is a powerful gasotransmitter/vasodilator, which has been shown by us and others, to possess protective effects against preeclampsia in vitro and in vivo (PMID: 30315766, PMID: 24335973).
The premise is that novel compounds such as mitochondrial-targeted H2S donors (mtH2SD) will target both the mitochondrial impairment associated with oxidative stress and the maternal hypertension, thereby acting on multiple components underlying the pathophysiology of preeclampsia. Our collaborator, professor Matt Whiteman at Exeter University England, has developed unique mtH2SDs, which have received considerable media attention (e.g. Nature, BBC, Telegraph, CNN, Wall Street Journal, Bloomberg). The mtH2SDs typically present therapeutic and dose-dependent efficacy at >1,000-fold lower concentrations (e.g. 10-200 nM) or doses (e.g. 0.07-1mg/kg) than commonly used H2S donors. These molecules in vitro and in vivo (e.g. ADME/PK, stability, toxicity etc.) consistently show stimulation/restoration of mitochondrial respiration and ATP preservation of synthesis during extensive oxidative stress. Importantly, mtH2SDs have been used and shown protective effects in in vivo models of hypertension, myocardial and renal ischemia-reperfusion injury, organ transplantation, brain damage following cardiac arrest/CPR, stroke, burn injury, COPD, and asthma etc. Our proposed experiments are to investigate the therapeutic potential of mitochondrial-targeted mtH2SD in preeclampsia using unique compounds.