Hydrogen sulphide reduces renal ischemia-reperfusion injury by enhancing autophagy and reducing oxidative stress.

Abstract

Aim: Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury. Hydrogen sulphide (H₂S) exerts a protective effect in renal IRI. The present study was carried out to investigate the effects of exogenous H₂S on renal IRI by regulating autophagy in mice.

Methods: Mice were randomly assigned to control, IRI and NaHS (an H₂S donor, 28, 56 and 100 μmol/kg) groups. Renal IRI was induced by clamping the bilateral renal pedicles with non-traumatic arterial clamp for 45 min and then reperfused for 24 h. Mice were administered intraperitoneally with NaHS 20 min prior to renal ischemia. Sham group mice underwent the same procedures without clamping. Serum and kidney tissues were harvested 24 h after reperfusion for functional, histological, oxidative stress, and autophagic determination.

Results: Compared with the control group, the concentrations of serum creatinine (Scr), blood urea nitrogen (BUN), and malondialdehyde (MDA), the protein levels of LC3II/I, Beclin-1 and P62, as well as the number of autophagosomes were significantly increased, but the activity of superoxide dismutase (SOD) was decreased after renal IRI. NaHS pre-treatment dramatically attenuated renal IRI-induced renal dysfunction, histological changes, MDA concentration and p62 expression in a dose-dependent manner. However, NaHS increased the SOD activity and the protein levels of LC3II/I and Beclin-1.

Conclusion: These results indicate that exogenous H₂S protects the kidney from IRI through enhancement of autophagy and reduction of oxidative stress. Novel H₂S donors could be developed in the treatment of renal IRI.