L-alpha-glycerylphosphorylcholine reduces the microcirculatory dysfunction and nicotinamide adenine dinucleotide phosphate-oxidase type 4 induction after partial hepatic ischemia in rats

Hartmann, Petra; Fet, Ngwi; Garab, Dénes; Szabó, Andrea; Kaszaki, József; Srinivasan, Pramod Kadaba; Tolba, René; Boros, Mihály

doi:10.1016/j.jss.2013.12.025

Cited by 12 publications

(16 citation statements)

References 42 publications

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“…It is currently used in clinical practice to enhance functional recovery after cerebral stroke [10], and to reduce the cognitive symptoms of dementia [27, 12]. Exogenous GPC is detected in the circulation one hour after an iv injection, it passes through the blood-brain barrier, stimulates PC biosynthesis, and activates postsynaptic cholinergic receptors [9, 13, 28]. Tissue distribution studies have shown that GPC and its metabolites are particularly accumulated in organs of excretion (kidney/liver), but the liver contains the highest concentration [9, 13].…”

Section: Discussionmentioning

confidence: 99%

“…Exogenous GPC is detected in the circulation one hour after an iv injection, it passes through the blood-brain barrier, stimulates PC biosynthesis, and activates postsynaptic cholinergic receptors [9, 13, 28]. Tissue distribution studies have shown that GPC and its metabolites are particularly accumulated in organs of excretion (kidney/liver), but the liver contains the highest concentration [9, 13]. Cellular uptake of GPC may occur by osmoregulation or under the control of an active transport system [29].…”

Section: Discussionmentioning

confidence: 99%

“…Under physiological conditions, GPC can be involved in the preservation of the structural integrity of the cellular membranes, probably through the stimulation of PC synthesis via the Kennedy pathway [11]. Earlier studies from our laboratory have demonstrated that GPC administration can reduce several signs of oxidative and inflammatory tissue damage in experimental IR models [12, 13]. The anti-inflammatory action of a potentially parasympathomimetic compound is an interesting finding, because that targets the inflammatory cascade without the confounding effects of mediators deriving from the metabolism of the lipid side-chains [14].…”

Section: Introductionmentioning

confidence: 99%

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Targeting Mitochondrial Dysfunction with L-Alpha Glycerylphosphorylcholine

et al. 2016

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BackgroundWe hypothesized that L-alpha-glycerylphosphorylcholine (GPC), a deacylatedphosphatidylcholine derivative, can influence the mitochondrial respiratory activity and in this way, may exert tissue protective effects.MethodsRat liver mitochondria were examined with high-resolution respirometry to analyze the effects of GPC on the electron transport chain in normoxic and anoxic conditions. Besides, Sprague-Dawley rats were subjected to sham operation or standardized liver ischemia-reperfusion (IR), with or without GPC administration. The reduced glutathione (GSH) and oxidized glutathione disulfide (GSSG), the tissue myeloperoxidase, xanthine oxidoreductase and NADPH oxidases activities were measured. Tissue malondialdehyde and nitrite/nitrate formation, together with blood superoxide and hydrogen-peroxide production were assessed.ResultsGPC increased the efficacy of complex I-linked mitochondrial oxygen consumption, with significantly lower in vitro leak respiration. Mechanistically, liver IR injury was accompanied by deteriorated mitochondrial respiration and enhanced ROS production and, as a consequence, by significantly increased inflammatory enzyme activities. GPC administration decreased the inflammatory activation in line with the reduced oxidative and nitrosative stress markers.ConclusionGPC, by preserving the mitochondrial complex I function respiration, reduced the biochemical signs of oxidative stress after an IR episode. This suggests that GPC is a mitochondria-targeted compound that indirectly suppresses the activity of major intracellular superoxide-generating enzymes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Targeting Mitochondrial Dysfunction with L-Alpha Glycerylphosphorylcholine

et al. 2016

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“…We have also shown that CH4-producing phospholipid substrates inhibit the formation of ROS proportional to the amount of CH4 generated and the number of methyl groups in the molecules . It is especially notable that liver concentrations of endogenous GPC are significantly depleted after hemorrhagic shock, a prototype of systemic IR injury (Scribner 2010), and previous data suggest that exogenous GPC may influence tissue reactions in IR injury (Tőkés 2015;Hartmann 2014;. Thus, the possible anti-inflammatory and scavenging potential of GPC is of particular importance, because it could offer means of targeting the inflammatory cascade without the confounding effects of mediators deriving from the metabolism of lipid side-chains.…”

Section: Biological and Anti-inflammatory Effects Of L-alpha Glycerylmentioning

confidence: 99%

“…Complete ischemia of the median and left hepatic lobes was achieved by clamping the left lateral branches of the hepatic artery and the portal vein with a microsurgical clip for 60 min. After the period of ischemia, the clips were removed and measurements were performed during a 60-min reperfusion period (Hartmann 2014). The wound was temporarily covered with nonwater-permeable foil during the reperfusion period.…”

Section: Surgical Proceduresmentioning

confidence: 99%

Pathomechanism and therapeutic possibilities of mitochondrial dysfunction in ischemia-reperfusion

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l-Alpha-glycerylphosphorylcholine can be cytoprotective or cytotoxic in neonatal rat cardiac myocytes: a double-edged sword phenomenon

et al. 2019

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l-Alpha-glycerylphosphorylcholine (GPC) is a widely used food supplement. GPC has been shown to exert beneficial effects in several organs; however, the cardiac effects of GPC have yet to be investigated. The aim of the present study was therefore to map out the effects of GPC on cardiac myocytes, with or without ischemia–reperfusion insult. Neonatal rat cardiac myocytes were treated with GPC at 1, 10, 80, and 100 µM concentrations for 15 min, 3 h, or 24 h, respectively. Cell viability by calcein assay and the degree of oxidative stress by DHE (superoxide level) and H2DCF (total ROS accumulation) staining were measured. In separate experiments, cardiomyocytes were pre-treated with the optimal concentration of GPC for 3 h and then cells were exposed to 4 h of simulated ischemia followed by 2 h of reperfusion (SI/R). Cell viability was measured at the end of the SI/R protocol. In normoxic conditions, the 15-min and the 3-h GPC treatment did not affect cell viability, total ROS, and superoxide levels. Under SI/R conditions, the 3-h GPC treatment protected the cardiac myocytes from SI/R-induced cell death and did not alter the level of oxidative stress. The 24-h GPC treatment in normoxic conditions resulted in significant cell death and increased oxidative stress at each concentration. Here we provide the first evidence for the cytoprotective effect of short-term GPC treatment. However, long-term administration of GPC may exert cytotoxicity in a wide concentration range in cardiac myocytes. These results may draw attention to a comprehensive cardiac safety protocol for the testing of GPC.Electronic supplementary materialThe online version of this article (10.1007/s11010-019-03580-1) contains supplementary material, which is available to authorized users.

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L-alpha-glycerylphosphorylcholine reduces the microcirculatory dysfunction and nicotinamide adenine dinucleotide phosphate-oxidase type 4 induction after partial hepatic ischemia in rats

Cited by 12 publications

References 42 publications

Targeting Mitochondrial Dysfunction with L-Alpha Glycerylphosphorylcholine

Targeting Mitochondrial Dysfunction with L-Alpha Glycerylphosphorylcholine

Pathomechanism and therapeutic possibilities of mitochondrial dysfunction in ischemia-reperfusion

l-Alpha-glycerylphosphorylcholine can be cytoprotective or cytotoxic in neonatal rat cardiac myocytes: a double-edged sword phenomenon

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