Hydrogen sulfide prevents renal ischemia-reperfusion injury in CLAWN miniature swine

Background Hydrogen sulfide (H₂S) has recently been reported to demonstrate both antiinflammatory and cytoprotective effects; however, its efficacy has not been well documented in large animal models. In this study, we examined whether the administration of H₂S offers cytoprotective effects on renal ischemia-reperfusion injury (IRI) in a preclinical miniature swine model. Methods Major histocompatibility complex-inbred, CLAWN miniature swine (n = 9) underwent a right nephrectomy, followed by induction of a 120-min period of warm ischemia via placement of clamps on the left renal artery and vein. Group 1 (n = 3) underwent renal ischemia without H₂S administration. Groups 2 (n = 3) and 3 (n = 3) received Na₂S (prodrug of H₂S) 10 min before reperfusion of the ischemic kidneys followed by a 30-min of Na₂S postreperfusion intravenously (group 2) or selective administration of Na₂S via the left renal artery (group 3). IRI was assessed by kidney biopsies, levels of inflammatory cytokines in sera and kidney tissue. Results Animals in group 1 had significantly higher serum creatinine levels compared with animals in groups 2 and 3 (P < 0.01). Histology showed severe tubular damage with TUNEL-positive cells in group 1 on postoperative day 2 compared with mild damage in group 2 and minimal damage in group 3. Furthermore, levels of inflammatory cytokines in both serum (interleukin-6 [IL-6], tumor necrosis factor-α, and high-mobility group box 1) and renal tissue (IL-1 and IL-6) in group 3 were markedly lower than in group 2, suggesting beneficial effects of selective Na₂S administration. Conclusions Na₂S administration, especially via an organ selective approach, appears to potentially offer cytoprotective and antiinflammatory effects following renal IRI.