S-Adenosylmethionine does not Reduce Ischaemia-Reperfusion Injury to a Marginal Liver Graft in an In vivo Experiment

2011 ◽  
Author(s):  
Tomas Pantoflicek ◽  
Eva Koblihova ◽  
Miroslav Ryska
Keyword(s):  
Reperfusion Injury ◽  
Liver Graft ◽  
Ischaemia Reperfusion Injury ◽  
In Vivo Experiment ◽  
Ischaemia Reperfusion

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.

Involvement of the HIF-1α and Wnt/β-catenin pathways in the protective effects of losartan on fatty liver graft with ischaemia/reperfusion injury

2013 ◽  
Vol 126 (2) ◽  
pp. 163-174 ◽  
Author(s):  
Ying-Ying Yang ◽  
Pei-Chang Lee ◽  
Yi-Tsau Huang ◽  
Wei-Ping Lee ◽  
Ying-Ju Kuo ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Elevated Serum ◽  
Liver Graft ◽  
Signalling Pathways ◽  
Protective Agent ◽  
Ischaemia Reperfusion Injury ◽  
Positive Effects ◽  
Ischaemia Reperfusion ◽  
Hepatic Congestion ◽  
Pre Treatment

Besides cardioprotective effects, the AT1R (angiotensin-II type 1 receptor) antagonist losartan protects the liver from IRI [IR (ischaemia/reperfusion) injury], but the mechanism has not been fully determined. The HIF (hypoxia inducible factor)-1α and Wnt/β-catenin signalling pathways have been reported to be involved in the mechanism of liver IRI. Therefore the aim of the present study was to determine whether the Wnt/HIF axis is part of the mechanism of the positive effect of AngII inhibition by losartan in liver IRI in rats. Various measurements were made in MCD/HF-NASH (methionine- and choline-deficient-diet/high-fat-diet-induced non-alcoholic steatohepatitis) rats with liver IRI. Acute losartan pre-administration markedly reversed the IR-suppressed levels of the hepatic-protective factors IL (interleukin)-6, IFN (interferon)-γ, Wnt3a, β-catenin and HIF-1α, and decreased hepatic blood flow and IR-elevated serum ALT (alanine aminotransferase), hepatic TNF (tumour necrosis factor)-α, IL-1α, hepatic congestion, vacuolization and necrosis, hepatic Suzuki IRI scores, necrotic index and levels of TBARS (thiobarbituric acid-reacting substances) in MCD/HF-NASH rats. Furthermore, acute Wnt3a pre-treatment significantly inhibited IR-elevated serum ALT, hepatic Suzuki IRI scores and TBARS, and restored the IR-depleted β-catenin/HIF-1α activity in MCD/HF-NASH rats. Simultaneous acute sFRP2 (secreted frizzled-related protein 2; a Wnt3a inhibitor) pre-treatment eliminated the losartan-related beneficial effects in MCD/HF-NASH rats with liver IRI, which was accompanied by a decrease in hepatic HIF-1α/β-catenin activity. Losartan-induced up-regulation of HIF-1α and Wnt/β-catenin signalling was associated with the recovery of IR-inhibited hepatic Bcl-2, Mn-SOD (manganese superoxide), Cu/Zn-SOD (copper/zinc superoxide) and GSH levels, and the suppression of IR-increased hepatic catalase and caspase 3/caspase 8 levels in MCD/HF-NASH rats. In conclusion, up-regulation of the HIF-1α and Wnt/β-catenin signalling pathways are part of the mechanism of the positive effects of losartan-related AngII inhibition in MCD/HF-NASH rats with liver IRI. Our study highlights the potential of the dual-organ protective agent losartan in NASH patients with steatotic livers and cardiovascular risk.

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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