Ian Lobb1, Justin Zhu2, Weihua Liu3, Aaron Haig3, Zhu Lan4, Alp Sener5. 1. Department of Microbiology and Immunology, Western University, London, ON; ; Schulich School of Medicine and Dentistry, Western University, London, ON; ; Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Centre, London, ON. 2. Schulich School of Medicine and Dentistry, Western University, London, ON; 3. Department of Pathology, Western University, London, ON; 4. Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Centre, London, ON. 5. Department of Microbiology and Immunology, Western University, London, ON; ; Schulich School of Medicine and Dentistry, Western University, London, ON; ; Department of Surgery, Western University; ; Multi-Organ Transplant Program, London Health Sciences Centre; ; Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Centre, London, ON.
Abstract
INTRODUCTION: The incidence of renal cell carcinoma (RCC) continues to rise concurrently with the increased prevalence of end-stage 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 afflicted kidney. We have recently demonstrated that hydrogen sulfide (H2S), a novel endogenous gaseous molecule, protects against prolonged cold and short-term warm renal IRI. In the current study, we examined whether exogenous H2S 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 (H2S group), and were compared against Sham-operated rats. RESULTS: H2S treatment improved long-term renal function as serum creatinine at day 7 was significantly decreased in the H2S group compared to IRI animals (p < 0.05). H2S treatment decreased the expression of pro-inflammatory 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 significant decrease (p < 0.05) in infiltration of macrophages at day 7 post-IRI compared to no treatment. CONCLUSION: H2S treatment improved long-term renal function and decreased long-term inflammation associated with warm IRI, and may offer a novel therapeutic approach to preventing warm IRI-induced renal injury associated with renal surgical procedures.
INTRODUCTION: The incidence of renal cell carcinoma (RCC) continues to rise concurrently with the increased prevalence of end-stage 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 afflicted kidney. We have recently demonstrated that hydrogen sulfide (H2S), a novel endogenous gaseous molecule, protects against prolonged cold and short-term warm renal IRI. In the current study, we examined whether exogenous H2S 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 (H2S group), and were compared against Sham-operated rats. RESULTS:H2S treatment improved long-term renal function as serum creatinine at day 7 was significantly decreased in the H2S group compared to IRI animals (p < 0.05). H2S treatment decreased the expression of pro-inflammatory 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 significant decrease (p < 0.05) in infiltration of macrophages at day 7 post-IRI compared to no treatment. CONCLUSION:H2S treatment improved long-term renal function and decreased long-term inflammation associated with warm IRI, and may offer a novel therapeutic approach to preventing warm IRI-induced renal injury associated with renal surgical procedures.
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