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].