Different dose-dependent effects of hydrogen sulfide on ischemia-reperfusion induced acute kidney injury in rats

Renal ischemia reperfusion (RIR) injury is a common clinical syndrome that affects renal function and significantly increases morbidity and mortality. Hydrogen sulfide (H2S) is an endogenously gaseous mediator that exhibits many cytoprotective effects. Recently, studies have shown that H2S have opposite effects in different doses. Therefore, in the current study we investigated the effects of H2S at different doses on renal function after induced renal ischemia reperfusion injury model.
The present study is an experimental study in animals and was conducted in Tehran University of Medical Sciences in April 2014. Male Wistar rats were assigned to five main groups (n= 6): 1) Sham, 2) Ischemia reperfusion (IR), 3) Administration of 50 µmol/kg Sodium hydrosulfide (NaHS), 4) Administration of 75 µmol/kg NaHS and 5) Administration of 125 µmol/kg NaHS. Sham group underwent laparotomy without cross-clamping of renal pedicles. Renal ischemia (IR) was induced in rats by both renal arteries occlusion for 55 min followed by reperfusion. Rats in the NaHS groups received intraperitoneal injections of 50, 75, or 125 µmol/kg of NaHS 10 minutes before the onset of ischemia and immediately after the onset of reperfusion. After reperfusion, plasma was collected for functional evaluation.
Compared to the sham, IR animals demonstrated a significant rise in plasma creatinine and BUN levels. Rats in the low-dose NaHS treated groups (H50, H75) had improved renal function by significantly decrease of creatinine and BUN levels. However, treatment with a high-dose of NaHS increased the levels of plasma creatinine and BUN levels as compared with these indices in the IR group.
Our study demonstrates that different doses of Sodium hydrosulfide (NaHS) can play diverse role in renal ischemia reperfusion injury. However, NaHS in the low-doses could protect the kidney from the RIR injury, in a higher dose NaHS exaggerated the renal function by increases plasma creatinine and BUN. Therefore, determining of the therapeutic doses of NaHS may be important in the protection of kidney from the RIR injury.