Glycine but not gadolinium chloride or methyl palmitate reduces postischemic white blood cell accumulation and early graft nonfunction after liver transplantation in the rat

Rentsch, Markus; Beham, A.; Sirek, S; Iesalnieks, Igors; Geissler, Edward K.; Anthuber, M; Jauch, Karl Walter

doi:10.1016/s0041-1345(02)03281-5

Cited by 5 publications

(3 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This was accompanied by significantly better survival as compared to control, Gadolinium Chloride and methyl palmitate groups. This study is important in that it shows that glycine ameliorates early (KC based) as well as late (neutrophil based) phases of hepatic IRI [89].…”

Section: Experience With Animal Liver Trans-plantationmentioning

confidence: 88%

The Role of Glycine in Hepatic Ischemia-Reperfusion Injury

Habib¹,

Hodgson²,

Davidson

2006

CPD

View full text Add to dashboard Cite

Glycine is a non-essential amino acid which is cheap, easily available and relatively non-toxic. It is composed of a single carbon attached to an amino and a carboxyl group, with a molecular weight of 75. It is involved in the production of bile, nucleic acids, porphyrins and creatine phosphate. It is part of the normal human diet and is used clinically, as an irrigant solution in urological and gynaecological procedures. Glycine has broad spectrum anti-inflammatory, cytoprotective and immunomodulatory properties whose therapeutic role has largely been un-investigated. Since the demonstration of its cytoprotective effect on hypoxic cultured renal tubule cells, further research has established its mechanism of anti-inflammatory action, which depends on stimulation of glycine sensitive chloride channel receptors on the cell membrane. The mechanism of non-specific cytoprotective effect which is present even in chloride and calcium free media is not clear. However glycine is currently being used experimentally, in human liver transplant recipients and has been shown to be beneficial in animal models of ischemia-reperfusion injury (IRI) in liver and several other organs. This review addresses the properties of glycine, its mechanism of action and its role in modulating IRI with special reference to the liver, with the aim of stimulating translational research into the potential role of glycine as a pharmaceutical agent.

show abstract

Section: Experience With Animal Liver Trans-plantationmentioning

confidence: 88%

The Role of Glycine in Hepatic Ischemia-Reperfusion Injury

Habib¹,

Hodgson²,

Davidson

2006

CPD

View full text Add to dashboard Cite

show abstract

“…Also in animal models of endotoxine and hemorrhagic shock, glycine modulation of Kupffer cells and inhibition of TNFα-secretion seem to be crucial for its beneficial effects (Mauriz et al, 2001; Neyrinck et al, 2005; Wang et al, 2004; Yang et al, 2001; Zhong et al, 1999). On the other hand, it was shown that destruction of Kupffer cells by gadolinium chloride (GdCl) was far less potent than glycine in animal liver transplantation studies, suggesting that not all in vivo findings can be explained by modulation of Kupffer cells (Rentsch et al, 2002, 2005). Also, in animal models of cholestasis, where bile cannot flow from the liver to the duodenum it was shown that beneficial glycine effects (lowering of TNFα levels, liver necrosis and liver enzymes) remained when Kupffer cells were destructed by GdCl (Fang et al, 2003; Froh et al, 2008).…”

Section: Hepatocytesmentioning

confidence: 99%

Glycine and glycine receptor signalling in non-neuronal cells

Eynden

2009

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Glycine is an inhibitory neurotransmitter acting mainly in the caudal part of the central nervous system. Besides this neurotransmitter function, glycine has cytoprotective and modulatory effects in different non-neuronal cell types. Modulatory effects were mainly described in immune cells, endothelial cells and macroglial cells, where glycine modulates proliferation, differentiation, migration and cytokine production. Activation of glycine receptors (GlyRs) causes membrane potential changes that in turn modulate calcium flux and downstream effects in these cells. Cytoprotective effects were mainly described in renal cells, hepatocytes and endothelial cells, where glycine protects cells from ischemic cell death. In these cell types, glycine has been suggested to stabilize porous defects that develop in the plasma membranes of ischemic cells, leading to leakage of macromolecules and subsequent cell death. Although there is some evidence linking these effects to the activation of GlyRs, they seem to operate in an entirely different mode from classical neuronal subtypes.

show abstract

“…LPS, a potent stimulus for Kupffer cells (KC), is involved in priming and deterioration in I/RI [4][5][6] . Substantial evidence indicates that KC, the resident macrophages of the liver, play a central role in the pathogenesis of liver parenchyma cell damage during the reperfusion phase, because activated KC are capable of releasing numerous mediators for regulating hepatic microcirculation [7] , and microcirculatory disturbance is a key factor in enhanced susceptibility of the donor liver to reperfusion [8] .…”

Section: Introductionmentioning

confidence: 99%

Glycine blunts transplantative liver ischemia-reperfusion injury by downregulating interleukin 1 receptor associated kinase-4

Liu

Yan

et al. 2006

Acta Pharmacologica Sinica

View full text Add to dashboard Cite

Aim: To determine whether glycine could downregulate interleukin 1 receptor associated kinase-4 (IRAK-4) expression to interfere with lipopolysaccharides (LPS) signal transduction and blunt transplantative liver ischemia-reperfusion injury (I/RI). Methods: SD rats were randomly divided into two groups: donor animals of the glycine group (n=40) were given glycine (1.5 mL; 300 mmol/L, iv) 1 h before harvest, and the control group were treated with 1.5 mL physiological saline (n= 40). Orthotropic liver transplantation was then performed according to the Kamada technique. Ten animals in each group were followed up for 7 d after surgery to assess survival. The remaining animals in each group were divided into 3 subgroups (n=10) at 1h, 2 h and 6 h after portal vein reperfusion. Levels of LPS, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin in portal circulation, as well as IRAK-4 and TNF-α expression, NF-κB transcriptional activity and morphological study of liver tissues were analyzed. Results: Reperfusion resulted in a significant elevation of LPS concentrations in each group persisting to the end of our study. However, glycine, which led to improved survival rate and liver function, significantly alleviated liver parenchyma cell damage by downregulating IRAK-4, TNF-α expression and NF-κB transcriptional activity compared with the control group. Conclusion: Glycine can attenuate hepatic I/RI by downregulating IRAK-4 to interfere with LPS signal transduction.

show abstract

Glycine but not gadolinium chloride or methyl palmitate reduces postischemic white blood cell accumulation and early graft nonfunction after liver transplantation in the rat

Cited by 5 publications

References 13 publications

The Role of Glycine in Hepatic Ischemia-Reperfusion Injury

The Role of Glycine in Hepatic Ischemia-Reperfusion Injury

Glycine and glycine receptor signalling in non-neuronal cells

Glycine blunts transplantative liver ischemia-reperfusion injury by downregulating interleukin 1 receptor associated kinase-4

Contact Info

Product

Resources

About