Date: Sunday, June 2, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Despite the success of preservation solutions, Ischemia-Reperfusion (IR) injury remains a significant problem for all solid organ transplants. As a result, an important, unmet need in solid organ transplantation is the prevention of IR injury. At UW, our team has developed a novel, proprietary compound, PrC-210, which has demonstrated superior prevention of IR injury in preclinical studies as an oxygen free radical scavenger. Here we describe our initial findings in a murine model of kidney IR injury.
*Methods: C57/B6 mice underwent laparotomy with the left renal pedicle clamped for 30 minutes in order to induce ischemia-reperfusion injury. Right nephrectomy was performed at the time of surgery. Mice received a single systemic dose of PrC-210, PrC-211, or PrC-252 (aminothiols) 20 minutes before IR injury occurred. Animals were harvested 24 hours following IR injury. Blood and kidney tissue were collected for analysis. Kidney caspase-3 level (marker of cell death) and serum BUN were measured in animals.
*Results: A single systemic PrC-210 dose 20 minutes before IR injury resulted in an 84% reduction in IR-induced kidney caspase level (P<0.0001); no significant difference in kidney caspase level was seen between PrC-210 treated kidneys and kidneys that did not undergo IR injury. PrC-210 resulted in a profound reduction of serum BUN compared to untreated (P<0.0001), PrC-211 (P<0.0001), and PrC-252 (P<0.0001) treated groups. PrC-211 significantly reduced caspase levels compared to untreated and PrC-252 treated groups (P<0.003). However, PrC-211 and PrC-252 did not significantly decrease serum BUN compared to untreated groups.
*Conclusions: PrC-210 significantly reduced serum BUN and kidney caspase levels compared to untreated groups. PrC-210 appears to be an effective drug to prevent IR injury in transplantation. Future studies will investigate the efficacy of PrC-210 enhanced UW Solution in a rodent kidney transplant model.
To cite this abstract in AMA style:Bath N, Fahl W, III RRedfield. New Reactive Oxygen Species Scavenger Prevents Injury in Ischemia-Reperfusion Injury Model [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/new-reactive-oxygen-species-scavenger-prevents-injury-in-ischemia-reperfusion-injury-model/. Accessed May 7, 2021.
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