Sodium thiosulfate-supplemented UW solution protects renal grafts against prolonged cold ischemia-reperfusion injury in a murine model of syngeneic kidney transplantation

Introduction: Cold ischemia-reperfusion injury (IRI) is an inevitable event that increases post-transplant complications. We have previously demonstrated that supplementation of University of Wisconsin (UW) solution with non-FDA-approved hydrogen sulfide (H2S) donor molecules minimizes cold IRI and...

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Autores principales:	George J. Dugbartey, Max Y. Zhang, Winnie Liu, Aaron Haig, Patrick McLeod, Jacqueline Arp, Alp Sener
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Sodium thiosulfate (STS) Ischemia-reperfusion injury (IRI) Static cold storage (SCS) Kidney transplantation Graft and recipient survival Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/7d3467e7af2c419fa79bdbba39721394
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spelling	oai:doaj.org-article:7d3467e7af2c419fa79bdbba397213942021-11-18T04:43:39ZSodium thiosulfate-supplemented UW solution protects renal grafts against prolonged cold ischemia-reperfusion injury in a murine model of syngeneic kidney transplantation0753-332210.1016/j.biopha.2021.112435https://doaj.org/article/7d3467e7af2c419fa79bdbba397213942022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S075333222101221Xhttps://doaj.org/toc/0753-3322Introduction: Cold ischemia-reperfusion injury (IRI) is an inevitable event that increases post-transplant complications. We have previously demonstrated that supplementation of University of Wisconsin (UW) solution with non-FDA-approved hydrogen sulfide (H2S) donor molecules minimizes cold IRI and improves renal graft function after transplantation. The present study investigates whether an FDA-approved H2S donor molecule, sodium thiosulfate (STS), will have the same or superior effect in a clinically relevant rat model of syngeneic orthotopic kidney transplantation. Method: Thirty Lewis rats underwent bilateral nephrectomy followed by syngeneic orthotopic transplantation of the left kidney after 24-hour preservation in either UW or UW+STS solution at 4 °C. Rats were monitored to post-transplant day 14 and sacrificed to assess renal function (urine output, serum creatinine and blood urea nitrogen). Kidney sections were stained with H&E, TUNEL, CD68, and myeloperoxidase (MPO) to detect acute tubular necrosis (ATN), apoptosis, macrophage infiltration, and neutrophil infiltration. Result: UW+STS grafts showed significantly improved graft function immediately after transplantation, with improved recipient survival compared to UW grafts (p < 0.05). Histopathological examination revealed significantly reduced ATN, apoptosis, macrophage and neutrophil infiltration and downregulation of pro-inflammatory and pro-apoptotic genes in UW+STS grafts compared to UW grafts (p < 0.05). Conclusion: We show for the first time that preservation of renal grafts in STS-supplemented UW solution protects against prolonged cold IRI by suppressing apoptotic and inflammatory pathways, and thereby improving graft function and prolonging recipient survival. This could represent a novel clinically applicable therapeutic strategy to minimize the detrimental clinical outcome of prolonged cold IRI in kidney transplantation.George J. DugbarteyMax Y. ZhangWinnie LiuAaron HaigPatrick McLeodJacqueline ArpAlp SenerElsevierarticleSodium thiosulfate (STS)Ischemia-reperfusion injury (IRI)Static cold storage (SCS)Kidney transplantationGraft and recipient survivalTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 145, Iss , Pp 112435- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Sodium thiosulfate (STS) Ischemia-reperfusion injury (IRI) Static cold storage (SCS) Kidney transplantation Graft and recipient survival Therapeutics. Pharmacology RM1-950
spellingShingle	Sodium thiosulfate (STS) Ischemia-reperfusion injury (IRI) Static cold storage (SCS) Kidney transplantation Graft and recipient survival Therapeutics. Pharmacology RM1-950 George J. Dugbartey Max Y. Zhang Winnie Liu Aaron Haig Patrick McLeod Jacqueline Arp Alp Sener Sodium thiosulfate-supplemented UW solution protects renal grafts against prolonged cold ischemia-reperfusion injury in a murine model of syngeneic kidney transplantation
description	Introduction: Cold ischemia-reperfusion injury (IRI) is an inevitable event that increases post-transplant complications. We have previously demonstrated that supplementation of University of Wisconsin (UW) solution with non-FDA-approved hydrogen sulfide (H2S) donor molecules minimizes cold IRI and improves renal graft function after transplantation. The present study investigates whether an FDA-approved H2S donor molecule, sodium thiosulfate (STS), will have the same or superior effect in a clinically relevant rat model of syngeneic orthotopic kidney transplantation. Method: Thirty Lewis rats underwent bilateral nephrectomy followed by syngeneic orthotopic transplantation of the left kidney after 24-hour preservation in either UW or UW+STS solution at 4 °C. Rats were monitored to post-transplant day 14 and sacrificed to assess renal function (urine output, serum creatinine and blood urea nitrogen). Kidney sections were stained with H&E, TUNEL, CD68, and myeloperoxidase (MPO) to detect acute tubular necrosis (ATN), apoptosis, macrophage infiltration, and neutrophil infiltration. Result: UW+STS grafts showed significantly improved graft function immediately after transplantation, with improved recipient survival compared to UW grafts (p < 0.05). Histopathological examination revealed significantly reduced ATN, apoptosis, macrophage and neutrophil infiltration and downregulation of pro-inflammatory and pro-apoptotic genes in UW+STS grafts compared to UW grafts (p < 0.05). Conclusion: We show for the first time that preservation of renal grafts in STS-supplemented UW solution protects against prolonged cold IRI by suppressing apoptotic and inflammatory pathways, and thereby improving graft function and prolonging recipient survival. This could represent a novel clinically applicable therapeutic strategy to minimize the detrimental clinical outcome of prolonged cold IRI in kidney transplantation.
format	article
author	George J. Dugbartey Max Y. Zhang Winnie Liu Aaron Haig Patrick McLeod Jacqueline Arp Alp Sener
author_facet	George J. Dugbartey Max Y. Zhang Winnie Liu Aaron Haig Patrick McLeod Jacqueline Arp Alp Sener
author_sort	George J. Dugbartey
title	Sodium thiosulfate-supplemented UW solution protects renal grafts against prolonged cold ischemia-reperfusion injury in a murine model of syngeneic kidney transplantation
title_short	Sodium thiosulfate-supplemented UW solution protects renal grafts against prolonged cold ischemia-reperfusion injury in a murine model of syngeneic kidney transplantation
title_full	Sodium thiosulfate-supplemented UW solution protects renal grafts against prolonged cold ischemia-reperfusion injury in a murine model of syngeneic kidney transplantation
title_fullStr	Sodium thiosulfate-supplemented UW solution protects renal grafts against prolonged cold ischemia-reperfusion injury in a murine model of syngeneic kidney transplantation
title_full_unstemmed	Sodium thiosulfate-supplemented UW solution protects renal grafts against prolonged cold ischemia-reperfusion injury in a murine model of syngeneic kidney transplantation
title_sort	sodium thiosulfate-supplemented uw solution protects renal grafts against prolonged cold ischemia-reperfusion injury in a murine model of syngeneic kidney transplantation
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/7d3467e7af2c419fa79bdbba39721394
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Sodium thiosulfate-supplemented UW solution protects renal grafts against prolonged cold ischemia-reperfusion injury in a murine model of syngeneic kidney transplantation

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