Time-dependent renal protection by remote ischemic preconditioning through a hydrogen sulfide-mediated antioxidative and anti-inflammatory pathway.

Abstract

This study compared the protective effects of early (<1 h) and late (>24 h) remote ischemic pre-conditioning (RIPreC) against renal I/R injury and elucidated the key role of H₂S signaling in mediating RIPreC-induced renoprotection. Randomly fifty-six male rats were allocated into eight groups: sham, I/R, early RIPreC+I/R, late RIPreC+I/R, NaHS + early RIPreC+I/R, NaHS+late RIPreC+I/R, PAG+early RIPreC+I/R, and PAG+late RIPreC+I/R. Renal I/R was created by 60 min of renal pedicle occlusion, followed by 24 h of reperfusion. RIPreC was induced by three cycles of femoral artery occlusion and reperfusion, each lasting 5 min. Blood, urine, and kidney tissues were gathered after the reperfusion period. Renal I/R led to serious dysfunction, elevated FE_Na, reduced C_Cr and urine osmolality, increased oxidative stress, and histological damage. These changes were accompanied by downregulation of CBS and CSE and upregulation of NF-κB and TNF-α. Both early and late RIPreC preserved renal function, decreased total oxidant status, enhanced total antioxidant capacity, reduced inflammation, and ameliorated histological injury. Notably, late RIPreC provided greater protection than early RIPreC. Administration of NaHS enhanced the RIPreC effects, whereas PAG abolished them. RIPreC confers remarkable protection against renal I/R damage, with the late window proving more effective than the early window. The renoprotective effects of RIPreC are exerted by increasing the activation of the hydrogen sulfide (H₂S) signaling pathway through upregulation of CBS and CSE. Pharmacological enhancement of H₂S signaling may improve RIPreC's clinical utility in preventing acute kidney injury (AKI).