Influence of Fructose-1,6-Diphosphate on Endotoxin-Induced Lung Injuries in Sheep

Markov, Angel K.; Warren, Edw.; Cohly, Hari H. P.; Sauls, David J.; Skelton, Thomas N.

doi:10.1016/j.jss.2006.06.038

Cited by 9 publications

(3 citation statements)

References 34 publications

(53 reference statements)

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“…This question may point to the increased infiltration of inflammatory cells through the vascular wall, which can be potentiated by the dysfunctional endothelial barrier. We and others have reported that chronic endothelial dysfunction due to different pathologies could be linked to PH (25, 106, 145, 196). In our study, we focused on the product of hemolysis, heme.…”

Section: Pulmonary Vascular Permeabilitymentioning

confidence: 88%

Focus on Early Events: Pathogenesis of Pulmonary Arterial Hypertension Development

Rafikova

Ghouleh

Rafikov

2019

Antioxidants & Redox Signaling

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Significance: Pulmonary arterial hypertension (PAH) is a progressive disease of the lung vasculature characterized by the proliferation of all vascular wall cell types, including endothelial, smooth muscle, and fibroblasts. The disease rapidly advances into a form with extensive pulmonary vascular remodeling, leading to a rapid increase in pulmonary vascular resistance, which results in right heart failure. Recent Advances: Most current research in the PAH field has been focused on the late stage of the disease, largely due to an urgent need for patient treatment options in clinics. Further, the pathobiology of PAH is multifaceted in the advanced disease, and there has been promising recent progress in identifying various pathological pathways related to the late clinical picture. Critical Issues: Early stage PAH still requires additional attention from the scientific community, and although the survival of patients with early diagnosis is comparatively higher, the disease develops in patients asymptomatically, making it difficult to identify and treat early. Future Directions: There are several reasons to focus on the early stage of PAH. First, the complexity of late stage disease, owing to multiple pathways being activated in a complex system with intra-and intercellular signaling, leads to an unclear picture of the key contributors to the pathobiology. Second, an understanding of early pathophysiological events can increase the ability to identify PAH patients earlier than what is currently possible. Third, the prompt diagnosis of PAH would allow for the therapy to start earlier, which has proved to be a more successful strategy, and it ensures better survival in PAH patients. Antioxid. Redox Signal. 31, 933-953.

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Section: Pulmonary Vascular Permeabilitymentioning

confidence: 88%

Focus on Early Events: Pathogenesis of Pulmonary Arterial Hypertension Development

Rafikova

Ghouleh

Rafikov

2019

Antioxidants & Redox Signaling

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“…We initially hoped for the latter, but we reversed our views after not finding substantial protection, if any, in the experiments reported in this paper. Although each year fewer publications appear in support of hypoxic/ischemic protection by exogenous FBP[17,28,31,32,41], there has not been a total cessation. We therefore feel it is important to share data from our negative experiments, which support earlier impressions that FBP is not metabolized in brain tissue, most likely because it does not enter cells.…”

Section: Discussionmentioning

confidence: 99%

Fructose-1,6-bisphosphate does not preserve ATP in hypoxic–ischemic neonatal cerebrocortical slices

2008

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Fructose-1,6-bisphosphate (FBP), an endogenous intracellular metabolite in glycolysis, was found in many preclinical studies to be neuroprotective during hypoxia-ischemia (HI) when administered exogenously. We looked for HI neuroprotection from FBP in a neonatal rat brain slice model, using 14.1 Tesla 1 H / 31 P/ 13 C NMR spectroscopy of perchloric acid slice extracts to ask: 1) if FBP preserves high energy phosphates during HI; and 2) if exogenous [1-13 C]FBP enters cells and is glycolytically metabolized to [3-13 C]lactate. We also asked: 3) if substantial superoxide production occurs during and after HI, thinking such might be treatable by exogenous FBP's antioxidant effects. Superfused P7 rat cerebrocortical slices (350μm) were treated with 2 mM FBP before and during 30 min of HI, and then given four hours of recovery with an FBP-free oxygenated superfusate. Slices were removed before HI, at the end of HI, and at 1 and 4 hours after HI. FBP did not improve high energy phosphate levels or change 1 H metabolite profiles. Large increases in [3-13 C]lactate were seen with 13 C NMR, but the lactate fractional enrichment was always (1.1±0.5)%, implying that all of lactate's 13 C was natural abundance 13 C, that none was from metabolism of 13 C-FBP. FBP had no effect on the fluorescence of ethidium produced from superoxide oxidation of hydroethidine. Compared to control slices, ethidium fluorescence was 25% higher during HI and 50% higher at the end of recovery. Exogenous FBP did not provide protection or enter glycolysis. Its use as an antioxidant might be worth studying at higher FBP concentrations.

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“…Markov’s work on FBP protection has continued over many years, with publications appearing as recently as 2007 [36,37]. During the twenty years that followed his initial FBP experiments, many others, too many to report, studied FBP use in hypoxia, ischemia, and/or oxidative stress.…”

Section: Investigations Of Two Metabolites As Treatments In Oxidatmentioning

confidence: 99%

Metabolomics of Oxidative Stress in Recent Studies of Endogenous and Exogenously Administered Intermediate Metabolites

Liu

Litt

Segal

et al. 2011

IJMS

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Aerobic metabolism occurs in a background of oxygen radicals and reactive oxygen species (ROS) that originate from the incomplete reduction of molecular oxygen in electron transfer reactions. The essential role of aerobic metabolism, the generation and consumption of ATP and other high energy phosphates, sustains a balance of approximately 3000 essential human metabolites that serve not only as nutrients, but also as antioxidants, neurotransmitters, osmolytes, and participants in ligand-based and other cellular signaling. In hypoxia, ischemia, and oxidative stress, where pathological circumstances cause oxygen radicals to form at a rate greater than is possible for their consumption, changes in the composition of metabolite ensembles, or metabolomes, can be associated with physiological changes. Metabolomics and metabonomics are a scientific disciplines that focuse on quantifying dynamic metabolome responses, using multivariate analytical approaches derived from methods within genomics, a discipline that consolidated innovative analysis techniques for situations where the number of biomarkers (metabolites in our case) greatly exceeds the number of subjects. This review focuses on the behavior of cytosolic, mitochondrial, and redox metabolites in ameliorating or exacerbating oxidative stress. After reviewing work regarding a small number of metabolites—pyruvate, ethyl pyruvate, and fructose-1,6-bisphosphate—whose exogenous administration was found to ameliorate oxidative stress, a subsequent section reviews basic multivariate statistical methods common in metabolomics research, and their application in human and preclinical studies emphasizing oxidative stress. Particular attention is paid to new NMR spectroscopy methods in metabolomics and metabonomics. Because complex relationships connect oxidative stress to so many physiological processes, studies from different disciplines were reviewed. All, however, shared the common goal of ultimately developing “omics”-based, diagnostic tests to help influence therapies.

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Influence of Fructose-1,6-Diphosphate on Endotoxin-Induced Lung Injuries in Sheep

Cited by 9 publications

References 34 publications

Focus on Early Events: Pathogenesis of Pulmonary Arterial Hypertension Development

Focus on Early Events: Pathogenesis of Pulmonary Arterial Hypertension Development

Fructose-1,6-bisphosphate does not preserve ATP in hypoxic–ischemic neonatal cerebrocortical slices

Metabolomics of Oxidative Stress in Recent Studies of Endogenous and Exogenously Administered Intermediate Metabolites

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