Effect of PERLA®, a new cold-storage solution, on oxidative stress injury and early graft function in rat kidney transplantation model.

BACKGROUND: The composition of organ preservation solutions is crucial for maintaining graft integrity and early graft function after transplantation. The aim of this study is to compare new organ preservation solution PERLA® with the gold standard preservation solution University of Wisconsin (UW) regarding oxidative stress and early graft injury. METHODS: In order to assess oxidative stress after cold storage, kidney grafts have been preserved for 18 h at 4° C in either UW solution or PERLA® solution and then assessed for oxidative stress injury (protocol 1). To assess kidney injuries and oxidative stress after reperfusion, rat kidneys were harvested, stored in cold UW or in PERLA® solutions for 18 h at 4 °C and then transplanted heterotopically for 6 h (protocol 2). PERLA® is a high Na+/low K+ solution including PEG-35 (1 g/L), trimetazidine (1 µM), carvedilol (10 µM) and tacrolimus (5 µM). RESULTS: Our results showed that preservation of kidneys in PERLA® solution significantly attenuates oxidative stress parameters after cold storage and reperfusion. We found a significant decrease in oxidative damage indicators (MDA, CD and CP) and a significant increase in antioxidant indicators (GPx, GSH, CAT, SOD and PSH). Moreover, PERLA® solution decreased kidney injury after reperfusion (creatinine, LDH and uric acid). CONCLUSION: PERLA® solution was more effective than UW storage solution in preserving rat's kidney grafts.

Effect of oleuropein on oxidative stress, inflammation and apoptosis induced by ischemia-reperfusion injury in rat kidney.

AIMS: This study aimed to evaluate the effect of oleuropein (OLE), the main phenolic compound present in olive leaves, on kidney ischemia-reperfusion injury (IRI) and to explore the underlying protective mechanism. MAIN METHODS: Rat kidneys were subjected to 60 min of bilateral warm ischemia followed by 120 min of reperfusion. OLE was administered orally 48 h, 24 h and 30 min prior to ischemia at doses of 10, 50 and 100 mg/kg body weight. The creatinine, urea, uric acid concentrations and lactate dehydrogenase (LDH) activity in plasma were evaluated. Oxidative stress and inflammation parameters were also assessed. Renal expression of AMP-activated protein kinase (p-AMPK), endothelial nitric oxide synthase (eNOS), mitogen-activated protein kinases (MAPK), inflammatory proteins and apoptotic proteins were evaluated using Western blot. KEY FINDINGS: Our results showed that OLE at 50 mg/kg reduced kidney IRI as revealed by a significant decrease of plasmatic creatinine, urea, uric acid concentrations and LDH activity. In parallel, OLE up-regulated antioxidant capacities. Moreover, OLE diminished the level of CRP and the expression of cyclooxygenase 2 (COX-2). Finally, OLE enhanced AMPK phosphorylation as well as eNOS expression whereas MAPK, and cleaved caspase-3 implicated in cellular apoptosis were attenuated in the ischemic kidneys. SIGNIFICANCE: In conclusion, this study shows that OLE could be used as therapeutic agent to reduce IRI through its anti-oxidative, anti-inflammatory and anti-apoptotic properties.

Protective potential effects of fucoidan in hepatic cold ischemia-rerfusion injury in rats.

The necessity to increase the efficiency of organ preservation has pushed physicians to consider the use of pharmacological additives in preservation solutions to minimize ischemia reperfusion injury. Here, we evaluated the effect of fucoidan, sulfated polysaccharide from brown seaweed, as an additive to IGL-1 (Institut Georges Lopez) preservation solution. Livers from Wistar rats were preserved for 24 h at 4 °C in IGL-1 solution, enriched or not with fucoidan (100 mg/L). Thereafter, they were subjected to reperfusion (2 h, at 37 °C) using an isolated perfused rat liver model. The addition of fucoidan to IGL-1 solution reduced hepatic injury (AST, ALT) and improved liver function compared to IGL-1 solution without fucoidan. In addition, we noted a significant increase in the phosphorylation of AMPK, AKT protein kinase and GSK3-ß, leading to a reduction in VDAC phosphorylation, as well as a reduction in apoptosis (caspase 3), mitochondrial damage, oxidative stress and endoplasmic reticulum (ER) stress markers. Furthermore, ERK1/2 and P38 MAPKs phosphorylation significantly decreased after supplementation of IGL-1 solution with fucoidan. In conclusion, the supplementation of IGL-1 solution with fucoidan maintained liver graft integrity and function through the prevention of the ER stress, oxidative stress and mitochondrial dysfunction. Fucoidan could be considered as potential natural therapeutic agent to alleviate graft injury.