1. Sodium thiosulfate-supplemented UW solution protects renal grafts against prolonged cold ischemia-reperfusion injury in a murine model of syngeneic kidney transplantation
- Author
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Max Y. Zhang, George J. Dugbartey, Smriti Juriasingani, Masoud Akbari, Winnie Liu, Aaron Haig, Patrick McLeod, Jacqueline Arp, and Alp Sener
- Subjects
Male ,Ischemia-reperfusion injury (IRI) ,medicine.medical_specialty ,Static cold storage (SCS) ,Adenosine ,Allopurinol ,Organ Preservation Solutions ,Urology ,Thiosulfates ,Renal function ,Apoptosis ,RM1-950 ,Kidney Function Tests ,Blood Urea Nitrogen ,Kidney transplantation ,Raffinose ,Sodium thiosulfate (STS) ,medicine ,Animals ,Insulin ,Viaspan ,Blood urea nitrogen ,Acute tubular necrosis ,Pharmacology ,Kidney ,business.industry ,Cold Ischemia ,Graft and recipient survival ,General Medicine ,medicine.disease ,Glutathione ,Rats ,Transplantation ,Survival Rate ,medicine.anatomical_structure ,Rats, Inbred Lew ,Creatinine ,Reperfusion Injury ,Therapeutics. Pharmacology ,business ,Reperfusion injury - Abstract
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
- Published
- 2022