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

Journal Article

Background

Hydrogen sulfide (H2 S) 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 H2 S 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 H2 S administration. Groups 2 (n = 3) and 3 (n = 3) received Na2 S (prodrug of H2 S) 10 min before reperfusion of the ischemic kidneys followed by a 30-min of Na2 S postreperfusion intravenously (group 2) or selective administration of Na2 S 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 Na2 S administration.

Conclusions

Na2 S administration, especially via an organ selective approach, appears to potentially offer cytoprotective and antiinflammatory effects following renal IRI.

Full Text

Duke Authors

Cited Authors

  • Sekijima, M; Sahara, H; Miki, K; Villani, V; Ariyoshi, Y; Iwanaga, T; Tomita, Y; Yamada, K

Published Date

  • November 2017

Published In

Volume / Issue

  • 219 /

Start / End Page

  • 165 - 172

PubMed ID

  • 29078877

Pubmed Central ID

  • 29078877

Electronic International Standard Serial Number (EISSN)

  • 1095-8673

International Standard Serial Number (ISSN)

  • 0022-4804

Digital Object Identifier (DOI)

  • 10.1016/j.jss.2017.05.123

Language

  • eng