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.
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http://dx.doi.org/10.2174/1381612824666180807124356 | DOI Listing |
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Department of Physiology, College of Medicine, King Saud University, 12271, Riyadh, Saudi Arabia.
Ischemia-reperfusion injury (IRI) is a common pathogenic situation that arises throughout all liver surgeries, including liver transplants. We aimed to compare the preventive effects of valsartan (VST) against valsartan + sacubitril (LCZ696) on hepatic injury caused by IRI. A total of thirty-six male Westar albino rats were split into six groups randomly: sham, IRI, VST + IRI, LCZ696 + IRI, VST, and LCZ696.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
Recipients often suffer from hyperlactatemia during liver transplantation (LT), but whether hyperlactatemia exacerbates hepatic ischemia-reperfusion injury (IRI) after donor liver implantation remains unclear. Here, the role of hyperlactatemia in hepatic IRI is explored. In this work, hyperlactatemia is found to exacerbate ferroptosis during hepatic IRI.
View Article and Find Full Text PDFHepatic ischemia-reperfusion injury (IRI) poses a significant threat to clinical outcomes and graft survival during hemorrhagic shock, hepatic resection, and liver transplantation. Current pharmacological interventions for hepatic IRI are inadequate. In this study, we identified ginsenoside Rk2 (Rk2), a rare dehydroprotopanaxadiol saponin, as a promising agent against hepatic IRI through high-throughput screening.
View Article and Find Full Text PDFGastroenterol Res Pract
January 2025
Department of Hepatobiliary and Pancreatic Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Despite N-methyladenosine (mA) being closely involved in various pathophysiological processes, its potential role in liver injury is largely unknown. We designed the current research to study the potential role of fat mass and obesity-associated protein (FTO), an mA demethylase, on hepatic ischemia-reperfusion injury (IRI). Wild-type mice injected with an adeno-associated virus carrying fat mass and obesity-associated protein (AAV-FTO) or adeno-associated virus carrying green fluorescent protein (GFP) (AAV-GFP) were subjected to a hepatic IRI model in vivo.
View Article and Find Full Text PDFBioeng Transl Med
January 2025
Research Institute of Transplant Medicine, Tianjin First Central Hospital, School of Medicine, Nankai University Tianjin China.
Pump is a vital component for expelling the perfusate in small animal isolated organ normothermic machine perfusion (NMP) systems whose flexible structure and rhythmic contraction play a crucial role in maintaining perfusion system homeostasis. However, the continuous extrusion forming with the rigid stationary shaft of the peristaltic pumps can damage cells, leading to metabolic disorders and eventual dysfunction of transplanted organs. Here, we developed a novel biomimetic blood-gas system (BBGs) for preventing cell damage.
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