Glycine rinse protects against liver injury during transplantation

Arora, Amindra S.; Nichols, Jenna; Debernardi, Michael; Steers, Jeffery L.; Krom, R. A. F.; Gores, G. J.

doi:10.1016/s0041-1345(98)01729-1

Cited by 20 publications

(13 citation statements)

References 8 publications

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“…In 1999, Arora et al . reported that glycine rinse decreases injury of the transplanted liver (Arora et al ., 1999). In their study with a total number of 50 patients, livers were cold‐stored in UW solution.…”

Section: Clinical Application Of Glycinementioning

confidence: 99%

Glycine, a simple physiological compound protecting by yet puzzling mechanism(s) against ischaemia–reperfusion injury: current knowledge

Petrat

Boengler

Schulz

et al. 2012

British J Pharmacology

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Ischaemia is amongst the leading causes of death. Despite this importance, there are only a few therapeutic approaches to protect from ischaemia-reperfusion injury (IRI). In experimental studies, the amino acid glycine effectively protected from IRI. In the prevention of IRI by glycine in cells and isolated perfused or cold-stored organs (tissues), direct cytoprotection plays a crucial role, most likely by prevention of the formation of pathological plasma membrane pores. Under in vivo conditions, the mechanism of protection by glycine is less clear, partly due to the physiological presence of the amino acid. Here, inhibition of the inflammatory response in the injured tissue is considered to contribute decisively to the glycine-induced reduction of IRI. However, attenuation of IRI recently achieved in experimental animals by low-dose glycine treatment regimens suggests additional/other (unknown) protective mechanisms. Despite the convincing experimental evidence and the large therapeutic width of glycine, there are only a few clinical trials on the protection from IRI by glycine with ambivalent results. Thus, both the mechanism(s) behind the protection of glycine against IRI in vivo and its true clinical potential remain to be addressed in future experimental studies/clinical trials.

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Section: Clinical Application Of Glycinementioning

confidence: 99%

Glycine, a simple physiological compound protecting by yet puzzling mechanism(s) against ischaemia–reperfusion injury: current knowledge

Petrat

Boengler

Schulz

et al. 2012

British J Pharmacology

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“…The above-mentioned cytoprotective effects of glycine against liver ischemia were considered solid enough to trigger clinical trials. Preliminary studies with few patients were undertaken showing, in one first study, that 2 mM glycine added to the perfusion solution during transplantation induced a significant decrease in liver enzymes and evoked less complications (Arora et al, 1999). A second study with seven patients confirmed that a one-week long daily infusion of glycine post-operatively (corresponding to ∼2 mM plasma concentration) significantly decreased plasma liver enzyme levels (Schemmer et al, 2001, 2002).…”

Section: Hepatocytesmentioning

confidence: 99%

Glycine and glycine receptor signalling in non-neuronal cells

Eynden

2009

Front. Mol. Neurosci.

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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.

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“…Glycine has shown promise in reducing hepatic IRI in the limited clinical experience currently available ( Table 7). In a prospective, randomized, double blind, controlled trial involving 50 patients, dual vessel liver rinse with 2 mM glycine solution (150 ml and 350 ml, hepatic artery and portal vein respectively), just before reperfusion showed significantly reduced alanine aminotransferase (ALT) rise for the first 3 days, post orthotopic liver transplantation, and reduced incidence of complications, specially ischemic type biliary strictures [90]. Schemmer et al also conducted a study of glycine in human liver transplantation.…”

Section: Experience In Human Liver Transplanta-tionmentioning

confidence: 99%

The Role of Glycine in Hepatic Ischemia-Reperfusion Injury

Habib¹,

Hodgson²,

Davidson

2006

CPD

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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.

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Glycine rinse protects against liver injury during transplantation

Cited by 20 publications

References 8 publications

Glycine, a simple physiological compound protecting by yet puzzling mechanism(s) against ischaemia–reperfusion injury: current knowledge

Glycine, a simple physiological compound protecting by yet puzzling mechanism(s) against ischaemia–reperfusion injury: current knowledge

Glycine and glycine receptor signalling in non-neuronal cells

The Role of Glycine in Hepatic Ischemia-Reperfusion Injury

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