A Novel Preservation Solution Containing Quercetin and Sucrose for Porcine Kidney Transplantation

Abstract

Background. In organ transplantation, the University of Wisconsin (UW) solution has been the gold standard for organ preservation. Quercetin (Que) has numerous antioxidant and anti-inflammatory activities, and sucrose (Suc) may be effective for cold storage (CS). This study aimed to investigate the in vitro protective effect of Que and Suc on cold injury to the kidney and to determine whether Que + Suc could improve ischemia-reperfusion injury during CS and hypothermic oxygenated perfusion (HOPE) in autologous transplantation models. Methods. BHK-21 cells were stored at 4°C for 3 days in UW solution for CS/machine perfusion (CS/MP-UW) with Que (33.1 μM, 3.3 μM, 0.33 μM) and Suc (0.1 M). In a porcine model of renal autologous transplantation, left kidney grafts were preserved under 3 conditions: group 1, CS preservation for 24 hours; group 2, CS preservation for 22 hours and HOPE with CS/MP-UW solution for 2 hours; and group 3, identical preservation as group 2, with Que and Suc added to the solution. Animals were euthanized on day 7 after autologous transplantation. Results. After 3 days of CS preservation, the CS/MP-UW solution with Que (33.1 μM, 3.3 μM) and Suc showed significant cell protection against cold injury. In the porcine model of renal autologous transplantation, the last blood Cre level and the blood lipid hydroperoxide on posttransplantation day 2 were significantly different between group 1 and group 3. Moreover, the total endothelial, glomerular, tubular, interstitial (EGTI) histology score in the kidney tissue was also significantly different. Regarding the change in renal resistance in HOPE, the decrease observed in group 3 was significantly larger than that in group 2. Conclusions. Our results suggest that the addition of Que and Suc to a UW solution can improve kidney preservation and could potentially enhance the outcome of kidney transplantation.

Renal Delivery of Pharmacologic Agents During Machine Perfusion to Prevent Ischaemia-Reperfusion Injury: From Murine Model to Clinical Trials

“…Recently, Gochi M et al. showed the effects of Que and Scr in CS solution and hypothermic oxygenated perfusion (HOPE) in autologous transplantation models ( 116 ). They found that the addition of Que and Scr in preservation solution ameliorated renal function and reduced oxidative stress, preserving renal parenchyma ( 116 ).…”

“…showed the effects of Que and Scr in CS solution and hypothermic oxygenated perfusion (HOPE) in autologous transplantation models ( 116 ). They found that the addition of Que and Scr in preservation solution ameliorated renal function and reduced oxidative stress, preserving renal parenchyma ( 116 ). Despite these strong results, this study did not demonstrate that Que could exert beneficial effects in long term-outcome ( 116 ).…”

“…They found that the addition of Que and Scr in preservation solution ameliorated renal function and reduced oxidative stress, preserving renal parenchyma ( 116 ). Despite these strong results, this study did not demonstrate that Que could exert beneficial effects in long term-outcome ( 116 ). Therefore, clinical studies should be performed to investigate the effects of Que in terms of graft survival and recipient outcome.…”

Combating Ischemia-Reperfusion Injury with Micronutrients and Natural Compounds during Solid Organ Transplantation: Data of Clinical Trials and Lessons of Preclinical Findings

“…Similar results were obtained in the case of quercetin. In animal models, a decrease of oxidative stress after IRI was observed [ 91 , 97 , 98 , 99 ], reflected by lower levels of thiobarbituric acid reactive substances (TBARS) [ 100 ] and MDA [ 101 ] as well as an increased activity of antioxidant enzymes [ 101 ]. Additionally, the inhibition of IRI-induced inflammation [ 91 , 99 ] and apoptosis/ferroptosis [ 99 , 102 ], as well as the induction of autophagy [ 103 ], finally resulting in decreased tissue damage, and improved organ function has been observed [ 97 , 98 , 102 ].…”

“…[183,184] p.o. [185] improved organ function increased graft survival [183,184] anti-inflammatory effects shift towards Treg via activation of PPARγ [183,184] inhibition of macrophage recruitment [185] inhibition of MCP-1/IP-10 [185] improved organ function improved shortening of isograft [202] decreased serum LDH [202] improved liver biomarkers (AST, ALT) [202] anti-inflammatory effects decreased serum TNFα [202] decreased serum IL-1 [202] anti-oxidative stress increased SOD activity [202] increased SOD/LPO [202] Quercetin Kidney rat [91,[98][99][100][101] pig [97] in vitro [102] mouse [103] i.p. [91,[98][99][100][101]103] preservation solution [97] anti-oxidative effects [91,[97][98][99] decrease of TBARS [100] decreased MDA [101] increased level of antioxidant enzymes [101] anti-inflammatory effects [91,99] anti-apoptotic effects [99,102] induction of autophagy [103] Liver rat [98,<...>…”