Hypoxic preconditioning in renal ischaemia–reperfusion injury: a review in pre-clinical models

2021 ◽  
Vol 135 (23) ◽  
pp. 2607-2618
Author(s):  
Laurie Bruzzese ◽  
Gwénaël Lumet ◽  
Donato Vairo ◽  
Claire Guiol ◽  
Régis Guieu ◽  
...  

Abstract Ischaemia–reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and chronic kidney disease, which consists of cellular damage and renal dysfunction. AKI is a major complication that is of particular concern after cardiac surgery and to a lesser degree following organ transplantation in the immediate post-transplantation period, leading to delayed graft function. Because effective therapies are still unavailable, several recent studies have explored the potential benefit of hypoxic preconditioning (HPC) on IRI. HPC refers to the acquisition of increased organ tolerance to subsequent ischaemic or severe hypoxic injury, and experimental evidences suggest a potential benefit of HPC. There are three experimental forms of HPC, and, for better clarity, we named them as follows: physical HPC, HPC via treated-cell administration and stabilised hypoxia-inducible factor (HIF)-1α HPC, or mimicked HPC. The purpose of this review is to present the latest developments in the literature on HPC in the context of renal IRI in pre-clinical models. The data we compiled suggest that preconditional activation of hypoxia pathways protects against renal IRI, suggesting that HPC could be used in the treatment of renal IRI in transplantation.

2018 ◽  
Vol 24 (23) ◽  
pp. 2692-2700 ◽  
Author(s):  
H. Susana Marinho ◽  
Paulo Marcelino ◽  
Helena Soares ◽  
Maria Luísa Corvo

Background: Ischaemia-reperfusion injury (IRI), a major complication occurring during organ transplantation, involves an initial ischemia insult, due to loss of blood supply, followed by an inflammation-mediated reperfusion injury. A variety of molecular targets and pathways involved in liver IRI have been identified. Gene silencing through RNA interference (RNAi) by means of small interference RNA (siRNA) targeting mediators of IRI is a promising therapeutic approach. Objective: This study aims at reviewing the use of siRNAs as therapeutic agents to prevent IRI during liver transplantation. Method: We review the crucial choice of siRNA targets and the advantages and problems of the use of siRNAs. Results: We propose possible targets for siRNA therapy during liver IRI. Moreover, we discuss how drug delivery systems, namely liposomes, may improve siRNA therapy by increasing siRNA stability in vivo and avoiding siRNA off-target effects. Conclusion: siRNA therapeutic potential to preclude liver IRI can be improved by a better knowledge of what molecules to target and by using more efficient delivery strategies.


2015 ◽  
Vol 129 (4) ◽  
pp. 345-362 ◽  
Author(s):  
Jordi Gracia-Sancho ◽  
Araní Casillas-Ramírez ◽  
Carmen Peralta

Ischaemia/reperfusion injury is an important cause of liver damage during surgical procedures such as hepatic resection and liver transplantation, and represents the main cause of graft dysfunction post-transplantation. Molecular processes occurring during hepatic ischaemia/reperfusion are diverse, and continuously include new and complex mechanisms. The present review aims to summarize the newest concepts and hypotheses regarding the pathophysiology of liver ischaemia/reperfusion, making clear distinction between situations of cold and warm ischaemia. Moreover, the most updated therapeutic strategies including pharmacological, genetic and surgical interventions, as well as some of the scientific controversies in the field are described.


2021 ◽  
Vol 22 (14) ◽  
pp. 7523
Author(s):  
George Clarke ◽  
Hynek Mergental ◽  
Angus Hann ◽  
M. Thamara P. R. Perera ◽  
Simon C. Afford ◽  
...  

The increasing disparity between the number of patients listed for transplantation and the number of suitable organs has led to the increasing use of extended criteria donors (ECDs). ECDs are at increased risk of developing ischaemia reperfusion injury and greater risk of post-transplant complications. Ischaemia reperfusion injury is a major complication of organ transplantation defined as the inflammatory changes seen following the disruption and restoration of blood flow to an organ—it is a multifactorial process with the potential to cause both local and systemic organ failure. The utilisation of machine perfusion under normothermic (37 degrees Celsius) and hypothermic (4–10 degrees Celsius) has proven to be a significant advancement in organ preservation and restoration. One of the key benefits is its ability to optimise suboptimal organs for successful transplantation. This review is focused on examining ischaemia reperfusion injury and how machine perfusion ameliorates the graft’s response to this.


2010 ◽  
Vol 5 (2) ◽  
pp. 125-132 ◽  
Author(s):  
Inga Karu ◽  
Peeter Tahepold ◽  
Arno Ruusalepp ◽  
Joel Starkopf

2021 ◽  
pp. 1-9
Author(s):  
Hongmei Zhao ◽  
Yun Qiu ◽  
Yichen Wu ◽  
Hong Sun ◽  
Sumin Gao

<b><i>Introduction/Aims:</i></b> Hydrogen sulfide (H<sub>2</sub>S) is considered to be the third most important endogenous gasotransmitter in organisms. GYY4137 is a long-acting donor for H<sub>2</sub>S, a gas transmitter that has been shown to prevent multi-organ damage in animal studies. We previously reported the effect of GYY4137 on cardiac ischaemia reperfusion injury (IRI) in diabetic mice. However, the role and mechanism of GYY4137 in renal IRI are poorly understood. The aims of this study were to determine whether GYY4137 can effectively alleviate the injury induced by renal ischaemia reperfusion and to explore its possible mechanism. <b><i>Methods:</i></b> Mice received right nephrectomy and clipping of the left renal pedicle for 45 min. GYY4137 was administered by intraperitoneal injection for 2 consecutive days before the operation. The model of hypoxia/reoxygenation injury was established in HK-2 cells, which were pre-treated with or without GYY4137. Renal histology, function, apoptosis, and oxidative stress were measured. Western blot was used to measure the target ­protein after renal IRI. <b><i>Results:</i></b> The results indicated that GYY4137 had a clear protective effect on renal IRI as reflected by the attenuation of renal dysfunction, renal tubule injury, and apoptosis. Moreover, GYY4137 remarkably reduced renal IRI-induced oxidative stress. GYY4137 significantly elevated the nuclear translocation of nuclear factor-erythroid-2-related factor 2 (Nrf2) and the expression of antioxidant enzymes regulated by Nrf2, including SOD, HO-1, and NQO-1. <b><i>Conclusions:</i></b> GYY4137 alleviates ischaemia reperfusion-induced renal injury through activating the antioxidant effect mediated by Nrf2 signalling.


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