Hydrogen sulfie treatment ameliorates long-term renal dysfunction resulting from prolonged warm renal ischemia-reperfusion injury

Abstract

Introduction: The incidence of renal cell carcinoma (RCC) continues to rise concurrently with the increased prevalence of endstage renal disease worldwide. Treatment for small renal masses continues to be partial nephrectomy mostly involving the clamping of renal blood vessels. Although necessary, this technique results in warm renal ischemia and reperfusion injury (IRI) to the afflcted kidney. We have recently demonstrated that hydrogen sulfie (H 2S), a novel endogenous gaseous molecule, protects against prolonged cold and short-term warm renal IRI. In the current study, we examined whether exogenous H 2S has long-term protective effects against warm renal IRI associated with renal surgical procedures. Methods: Uni-nephrectomized Lewis rats underwent 1 hour of warm ischemia induced by clamping of the renal pelvis. Animals underwent either intraperitoneal treatment with phosphate buffered saline (PBS; IRI group) or PBS supplemented with 150 μM NaHS (H 2S group), and were compared against Sham-operated rats. Results:-2S treatment improved long-term renal function as serum creatinine at day 7 was signifiantly decreased in the H 2S group compared to IRI animals (p < 0.05). H 2S treatment decreased the expression of pro-inflmmatory markers TLR-4, TNF-α, IFNγ, IL-2 and ICAM-1, increased the expression of pro-survival molecule Bcl-2 and decreased the expression of pro-apoptotic marker BID at postoperative day 1. H2S-treated kidneys also showed a signifiant decrease (p < 0.05) in infitration of macrophages at day 7 post-IRI compared to no treatment. Conclusion:-H2S treatment improved long-term renal function and decreased long-term inflmmation associated with warm IRI, and may offer a novel therapeutic approach to preventing warm IRIinduced renal injury associated with renal surgical procedures.