Gene Silencing using siRNA for Preventing Liver Ischaemia-Reperfusion Injury

2018 ◽  
Vol 24 (23) ◽  
pp. 2692-2700 ◽  
Author(s):  
H. Susana Marinho ◽  
Paulo Marcelino ◽  
Helena Soares ◽  
Maria Luísa Corvo
Keyword(s):  
Gene Silencing ◽  
Reperfusion Injury ◽  
Therapeutic Potential ◽  
Major Complication ◽  
Ischaemia Reperfusion Injury ◽  
Small Interference Rna ◽  
Ischaemia Reperfusion ◽  
Promising Therapeutic Approach ◽  
Sirna Therapy

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.

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 ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Potential Benefit ◽  
Graft Function ◽  
Major Complication ◽  
Hypoxic Preconditioning ◽  
Cellular Damage ◽  
Post Transplantation ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion ◽  
Clinical Models

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.

Metabolic alterations in a rat model of hepatic ischaemia reperfusion injury: In vivo hyperpolarized 13 C MRS and metabolic imaging

2018 ◽  
Vol 38 (6) ◽  
pp. 1117-1127 ◽  
Author(s):  
Chung-Man Moon ◽  
Sang-Soo Shin ◽  
Nam-Yeol Lim ◽  
Seul-Kee Kim ◽  
Yang-Joon Kang ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Rat Model ◽  
Metabolic Imaging ◽  
Ischaemia Reperfusion Injury ◽  
Metabolic Alterations ◽  
Ischaemia Reperfusion

Effects of a new compound containing Palmitoylethanolamide and Baicalein in myocardial ischaemia/reperfusion injury in vivo

Phytomedicine ◽  
2019 ◽  
Vol 54 ◽  
pp. 27-42 ◽  
Author(s):  
Ramona D'amico ◽  
Roberta Fusco ◽  
Enrico Gugliandolo ◽  
Marika Cordaro ◽  
Rosalba Siracusa ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Myocardial Ischaemia ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion

The role of cycloxygenase-2 in the rodent kidney following ischaemia/reperfusion injury in vivo

2007 ◽  
Vol 562 (1-2) ◽  
pp. 148-154 ◽  
Author(s):  
Nimesh S.A. Patel ◽  
Salvatore Cuzzocrea ◽  
Massimo Collino ◽  
Prabal K. Chaterjee ◽  
Emanuela Mazzon ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion

The effect of relaxin on myocardial ischaemia-reperfusion injury and histamine release in vitro and in vivo

1996 ◽  
Vol 45 (S1) ◽  
pp. S27-S28 ◽  
Author(s):  
E. Masini ◽  
D. Salvemini ◽  
L. Mugnai ◽  
M. G. Bello ◽  
D. Bani ◽  
...  
Keyword(s):  
Histamine Release ◽  
Reperfusion Injury ◽  
Myocardial Ischaemia ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion ◽  
Release In Vitro

scholarly journals IL-4 Alleviates Ischaemia-Reperfusion Injury by Inducing Kupffer Cells M2 Polarization via STAT6-JMJD3 Pathway after Rat Liver Transplantation

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Minghua Deng ◽  
Jingyuan Wang ◽  
Hao Wu ◽  
Menghao Wang ◽  
Ding Cao ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Reperfusion Injury ◽  
Kupffer Cells ◽  
Interleukin 4 ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion ◽  
M2 Polarization ◽  
Hepatocellular Apoptosis

Background. Liver ischaemia-reperfusion injury (IRI) remains a problem in liver transplantation. Interleukin-4 (IL-4) has been found to reduce liver IRI, but the exact mechanism remains unclear. Methods. Donor livers were infused with recombinant IL-4 or normal saline during cold storage, and the hepatocellular apoptosis and the inflammatory response were detected. The effect of IL-4 treatment on Kupffer cells (KCs) polarization and expression of the STAT6-JMJD3 pathway was evaluated in vivo and in vitro. KCs in donor livers were depleted by clodronate liposome treatment or JMJD3 was inhibited by GSK-J4 before liver transplantation to determine whether the protective effect of IL-4 treatment was dependent on KCs. Results. IL-4 treatment decreased sALT and sAST levels and alleviated hepatocellular apoptosis and inflammation at 6 h after liver transplantation. IL-4 treatment induced KCs alternatively activated (M2) polarization in vitro and in vivo, and the expression of STAT6 and JMJD3 was increased. JMJD3 knockdown abolished KCs M2 polarization and reduced the antiapoptotic and anti-inflammatory effects induced by IL-4 treatment in vitro. In addition, the protection of IL-4 treatment against IRI induced by liver transplantation was significantly reduced after the depletion of KCs or the inhibition of JMJD3 in donor livers. Conclusions. IL-4 treatment-induced KCs M2 polarization was dependent on the STAT6-JMJD3 pathway and protected liver grafts from IRI after liver transplantation.

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