Liver Metabolomic Changes Identify Biochemical Pathways in Hemorrhagic Shock

Scribner, Drew M.; Witowski, Nancy E.; Mulier, Kristine E.; Lusczek, Elizabeth R.; Wasiluk, Karen R.; Beilman, Greg J.

doi:10.1016/j.jss.2010.07.046

Cited by 24 publications

(26 citation statements)

References 31 publications

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“…Mitochondrial dysfunction generates ROS and hypoxic conditions induce a leak of electrons of the ETC into the intermembranous space (Rose 2014), which can lead to increased ROS formation. We have demonstrated that GPC treatment reduces the leak respiration after an IR challenge, and in accordance with previous findings, the lower leak respiration was accompanied with a decreased ROS formation (Scribner 2010;Rose 2014;Kenneth 2005). Furthermore, exogenous GPC enhanced mitochondrial oxygen consumption both in normoxic and hypoxic conditions, which clearly demonstrates that GPC can potentiate the mitochondrial activity.…”

Section: Effects Of Gpc In Ros Productionsupporting

confidence: 92%

“…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%

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Pathomechanism and therapeutic possibilities of mitochondrial dysfunction in ischemia-reperfusion

Strifler¹

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Section: Effects Of Gpc In Ros Productionsupporting

confidence: 92%

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

confidence: 99%

Pathomechanism and therapeutic possibilities of mitochondrial dysfunction in ischemia-reperfusion

Strifler¹

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“…In subchronic or chronic studies and doses of 100 and 300 mg/kg bw, GPC did not alter the behavior, body weight, hematology, or clinical chemistry of rats and did not produce any signs of general toxicity. In hemorrhagic shock experiments (a prototype of systemic IR), concentrations of GPC significantly lower than the well tolerated dose caused rats to recover to baseline levels after 24 h. 10 GPC has proved effective against the loss of the membrane function in CNS injuries 11,12 and was previously tested as a centrally acting parasympathomimetic drug in dementia disorders and acute cerebrovascular diseases. [13][14][15] GPC, after oral administration, has been shown to cross the blood-brain barrier and reach the CNS, where it is incorporated into the phospholipid fraction of the neuronal plasma membrane and microsomes.…”

mentioning

confidence: 99%

l-Alpha Glycerylphosphorylcholine as a Potential Radioprotective Agent in Zebrafish Embryo Model

et al. 2016

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This work establishes the zebrafish embryo model for ionizing radiation (IR) modifier research and also evaluates the protective effect of L-alpha glycerylphosphorylcholine (GPC). Embryos were exposed to a single-fraction wholebody gamma irradiation (5, 10, 15, and 20 Gy) at different postfertilization time points and were serially assessed for viability and macro-and micromorphologic abnormalities. After toxicity evaluation, 194 lM of GPC was added for certain groups with 3-h incubation before the radiation. Nuclear factor kappa B (NF-jB) and interleukin-1b (IL-1b) expression changes were measured using quantitative real-time polymerase chain reaction. A higher sensitivity could be observed at earlier stages of the embryogenesis. The lethal dose (LD 50 ) for 6 hours postfertilization (hpf) embryos was 15 Gy and for 24 hpf was 20 Gy on day 7, respectively. GPC administration resulted in a significant improvement in both the distortion rate and survival of the 24 hpf embryos. Qualitative evaluation of the histological changes confirmed the protective effect of GPC. IL-1b and NF-jB overexpression due to 10 Gy irradiation was also reduced by GPC. GPC exhibited promising radioprotective effects in our zebrafish embryo model, decreasing the irradiationinduced morphological damage and lethality with significant reduction of IR-caused pro-inflammatory activation.

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“…CPF animals were given 7cc/kg bolus of Karo Syrup (mixture of sugars including ∼ 15% glucose, maltose, fructose and sucrose) diluted with water 1 hour prior to induction. The full experimental polytrauma and shock protocols have been described in detail previously [9], [10]. Briefly, animals were instrumented and splenectomized.…”

Section: Methodsmentioning

confidence: 99%

Fed State Prior to Hemorrhagic Shock and Polytrauma in a Porcine Model Results in Altered Liver Transcriptomic Response

et al. 2014

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Hemorrhagic shock is a leading cause of trauma-related mortality in both civilian and military settings. Resuscitation often results in reperfusion injury and survivors are susceptible to developing multiple organ failure (MOF). The impact of fed state on the overall response to shock and resuscitation has been explored in some murine models but few clinically relevant large animal models. We have previously used metabolomics to establish that the fed state results in a different metabolic response in the porcine liver following hemorrhagic shock and resuscitation. In this study, we used our clinically relevant model of hemorrhagic shock and polytrauma and the Illumina HiSeq platform to determine if the liver transcriptomic response is also altered with respect to fed state. Functional analysis of the response to shock and resuscitation confirmed several typical responses including carbohydrate metabolism, cytokine inflammation, decreased cholesterol synthesis, and apoptosis. Our findings also suggest that the fasting state, relative to a carbohydrate prefed state, displays decreased carbohydrate metabolism, increased cytoskeleton reorganization and decreased inflammation in response to hemorrhagic shock and reperfusion. Evidence suggests that this is a consequence of a shrunken, catabolic state of the liver cells which provides an anti-inflammatory condition that partially mitigates hepatocellar damage.

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Liver Metabolomic Changes Identify Biochemical Pathways in Hemorrhagic Shock

Cited by 24 publications

References 31 publications

Pathomechanism and therapeutic possibilities of mitochondrial dysfunction in ischemia-reperfusion

Pathomechanism and therapeutic possibilities of mitochondrial dysfunction in ischemia-reperfusion

l-Alpha Glycerylphosphorylcholine as a Potential Radioprotective Agent in Zebrafish Embryo Model

Fed State Prior to Hemorrhagic Shock and Polytrauma in a Porcine Model Results in Altered Liver Transcriptomic Response

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