Remote ischemic per-conditioning mitigates renal ischemia-reperfusion injury via hydrogen sulfide-mediated upregulation of Gclc and Gclm genes in male rats.

The aim of this study was to determine if remote ischemic per-conditioning (RIPerC) can provide protection to the kidneys from ischemia-reperfusion injury (IRI) by increasing the expression of the Gclc and Gclm genes involved in innate defenses. Rats undergoing sham surgery were used as controls. Induction of renal IRI involved blocking the renal pedicles for 60 min, then allowing 24 h of reperfusion. RIPerC involved 4 cycles (5 min) of limb I/R. Animals were divided into seven groups in a random manner: sham, I/R, I/R + RIPerC, I/R + NaHS (NaHS, 100 μmol /kg, i.p), I/R + RIPerC+NaHS, I/R + PAG (propargyl glycine, 50 mg/kg, i.p.) and I/R + RIPerC+PAG. Following reperfusion, samples of urine, blood, and renal tissue were gathered for functional, molecular, and histological analysis. Renal IRI impaired kidney function (reduced CCr, increased FENa, decreased water reabsorption, and reduced urine osmolality), increased oxidative stress (an increase in total oxidative status and a decrease in total antioxidant capacity), and reduced expression of CBS, CSE, Gclc and Gclm genes, causing tissue damage. RIPerC attenuated the IRI-induced kidney dysfunction, oxidative stress, and gene expression changes. Inhibiting hydrogen sulfide signaling with propargylglycine reduced the benefits of RIPerC, while the hydrogen sulfide donor NaHS enhanced them. These findings suggest RIPerC's renal protective effects involve upregulation of antioxidant defense pathways.