6.3 Nephroprotective effects of hydrogen sulfide
Renal ischemia-reperfusion injury (IRI) is a major predisposing factor for the development and progression of acute kidney injury (AKI)[145, 146]. AKI is a complex clinical syndrome characterized by a rapid decline in renal function, such as decreased glomerular filtration rate (GFR) with increased creatinine and urea nitrogen, water-electrolyte disturbances, acid-base imbalance, oliguria or even anuria[147, 148].AKI is often associated with serious complications, and the high mortality rate places a significant burden on the healthcare system[149]. Some recent studies have shown that H2S can improve renal function during IRI to prevent AKI, which seems to be associated with decreased levels of ROS expression[150-152]. In addition to antioxidant effects, H2S may also exert renoprotective effects through several other mechanisms. First, H2S can induce vascular relaxation through the opening of KATP channels in endothelial cells and renal vascular smooth muscle cells, thereby increasing renal blood flow[45, 153]. Second, it has been suggested that H2S has the potential to protect renal function by inhibiting angiotensin (Ang) II in the RAAS system[154]. In addition, some investigators have also found that A39, a mitochondrial-targeting H2S donor, can reduce ROS levels, protect mitochondrial function, and reduce renal epithelial cell injury, however, this protective effect is dose-dependent[155, 156].