Kidney

Hydrogen sulfide

Renal ischemia

Programmed cell death

Pyroptosis

Apoptosis

Ischemia

Cardiology

Acute kidney injury

Biochemistry

Caspase 1

Inflammasome

Organic chemistry

Necrosis

Inflammation

Internal medicine

Pharmacology

Sulfur

Cell damage

Medicine

Chemistry

Cell

Reperfusion injury

Pathology

Life Sciences

Ischemia-reperfusion (I/R)-induced acute kidney injury (AKI) shows high mortality. Hydrogen sulfide (H2S) is essential for regulating kidney function. This study explored the role and mechanism of H2S in I/R-induced AKI. I/R-induced mouse model and hypoxia/reoxygenation (H/R)-induced HK2 cell model of AKI were established and treated with NaHS (H2S donor), MCC950 (NLRP3 inhibitor) or DL-Propargylglycine (PAG, CSE inhibitor). Serum creatinine (Cr) and blood urea nitrogen (BUN) were measured to evaluate kidney function. The pathological changes of kidney tissues were detected. H2S level and H2S synthetase activity in kidney tissues were detected. Pyroptosis was assessed by pyroptotic cell numbers and pyroptosis-related protein levels determination. HK-2 cell viability and apoptosis were measured. NLRP3 protein level was detected. The role of NLRP3/Caspase-1 was verified in vivo and in vitro after MCC950 or PAG intervention. I/R-induced mice showed elevated levels of serum Cr and BUN, and obvious pathological changes, including severe tubular dilatation, tubular cell swelling, tubular epithelial cell abscission, tubular cell necrosis and inflammatory cell infiltration. H2S level and H2S synthetase activity were decreased. Increasing the level of H2S by NaHS improved the pathological changes of kidney tissues and limited the number of pyroptotic cells. In vitro, NaHS could reverse H/R-induced cell injury. H2S suppressed cell pyroptosis and kidney injury via inhibiting the NLRP3/Caspase-1 axis. We highlighted that H2S prevented cell pyroptosis via suppressing the NLRP3/Caspase-1 axis, thereby inhibiting I/R-induced AKI. These findings may confer novel insights for the clinical management of I/R-induced AKI.

Hydrogen sulfide reduces pyroptosis and alleviates ischemia-reperfusion-induced acute kidney injury by inhibiting NLRP3 inflammasome