Riboflavin Supplementation Improves Energy Metabolism in Mice Exposed to Acute Hypoxia

This study investigated the effects of riboflavin on energy metabolism in hypoxic mice. Kunming mice were fed diets containing riboflavin at doses of 6, 12, 24 and 48 mg/kg, respectively for 2 weeks before exposure to a simulated altitude of 6000 m for 8 h. Changes of riboflavin status and energy metabolism were assessed biochemically. Simultaneously, a 1H nuclear magnetic resonance (NMR) based metabolomic technique was used to track the changes of plasma metabolic profiling. It was found that the content of hepatic riboflavin was decreased and erythrocyte glutathione activation coefficient was elevated significantly under hypoxic condition. Meanwhile, increased plasma pyruvate, lactate, β-hydroxybutyrate and urea, as well as decreased plasma carnitine were observed. Riboflavin supplementation improved riboflavin status remarkably in hypoxic mice and decreased plasma levels of pyruvate, free fatty acids and β-hydroxybutyrate significantly. Plasma carnitine was increased in response to riboflavin supplementation. Results obtained from 1H NMR analysis were basically in line with the data from biochemical assays and remarkable changes in plasma taurine, choline and some other metabolites were also indicated. It was concluded that riboflavin requirement was increased under acute hypoxic condition and riboflavin supplementation was effective in improving energy metabolism in hypoxic mice.

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Faculty Opinions recommendation of Metabolic profiling of serum samples by 1H nuclear magnetic resonance spectroscopy as a potential diagnostic approach for septic shock.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718218113.793495669 ◽

2014 ◽

Author(s):

Anthony Gordon ◽

David Antcliffe

Keyword(s):

Septic Shock ◽

Nuclear Magnetic Resonance ◽

Magnetic Resonance ◽

Magnetic Resonance Spectroscopy ◽

Nuclear Magnetic Resonance Spectroscopy ◽

Metabolic Profiling ◽

Diagnostic Approach ◽

Resonance Spectroscopy ◽

Serum Samples ◽

1H Nuclear Magnetic Resonance

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Hypoxia Transcriptomic Modifications Induced by Proton Irradiation in U87 Glioblastoma Multiforme Cell Line

Journal of Personalized Medicine ◽

10.3390/jpm11040308 ◽

2021 ◽

Vol 11 (4) ◽

pp. 308

Author(s):

Valentina Bravatà ◽

Walter Tinganelli ◽

Francesco P. Cammarata ◽

Luigi Minafra ◽

Marco Calvaruso ◽

...

Keyword(s):

Glioblastoma Multiforme ◽

Cell Line ◽

Acute Hypoxia ◽

Hypoxic Condition ◽

Biological Processes ◽

Microarray Gene Expression ◽

Hypoxic Conditions ◽

Gene Expression Analyses ◽

Shed Light ◽

New Strategies

In Glioblastoma Multiforme (GBM), hypoxia is associated with radioresistance and poor prognosis. Since standard GBM treatments are not always effective, new strategies are needed to overcome resistance to therapeutic treatments, including radiotherapy (RT). Our study aims to shed light on the biomarker network involved in a hypoxic (0.2% oxygen) GBM cell line that is radioresistant after proton therapy (PT). For cultivating cells in acute hypoxia, GSI’s hypoxic chambers were used. Cells were irradiated in the middle of a spread-out Bragg peak with increasing PT doses to verify the greater radioresistance in hypoxic conditions. Whole-genome cDNA microarray gene expression analyses were performed for samples treated with 2 and 10 Gy to highlight biological processes activated in GBM following PT in the hypoxic condition. We describe cell survival response and significant deregulated pathways responsible for the cell death/survival balance and gene signatures linked to the PT/hypoxia configurations assayed. Highlighting the molecular pathways involved in GBM resistance following hypoxia and ionizing radiation (IR), this work could suggest new molecular targets, allowing the development of targeted drugs to be suggested in association with PT.

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Drug Action on the Metabolic Changes Induced by Acute Hypoxia on Synaptosomes from the Cerebral Cortex

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1982.23 ◽

1982 ◽

Vol 2 (2) ◽

pp. 229-239 ◽

Cited By ~ 14

Author(s):

G. Benzi ◽

E. Arrigoni ◽

O. Pastoris ◽

R. F. Villa ◽

M. Dossena ◽

...

Keyword(s):

Cerebral Cortex ◽

Acute Hypoxia ◽

Hypoxic Condition ◽

Creatine Phosphate ◽

Motor Area ◽

Cortical Motor ◽

Anesthetic Action ◽

Surface Freezing ◽

Cytidine Diphosphate

The synaptosomal fractions obtained from the motor area of the cerebral cortex of normocapnic, normoxic, or hypoxic, untreated beagle dogs and of pentobarbital (Nembutal®)- or cytidine diphosphate (CDP)-choline-treated dogs were incubated and analyzed for ATP, ADP, AMP, creatine phosphate, pyruvate, and lactate. The data were compared with data obtained by the surface freezing technique from the whole contralateral cortical area. The in vivo intracarotid perfusion of the drug differentially affected the content of the metabolites and their ratio. This occurred whether the evaluations were performed in the incubated synaptosomal preparations or in whole cerebral tissue, both during normoxia and after hypoxia (15 min; Pao2 = 17–19 mm Hg). Thus intracarotid perfusion of nembutal increased the synaptosomal phosphorylation state both in normoxic and in hypoxic animals, whereas the effect on the metabolism of the contralateral cortical motor area as a whole was in all cases less than that observed in the synaptosomal fraction. Perfusion with CDP-choline increased synaptosomal phosphorylation after the hypoxic condition, but had no effect in normoxia or on the whole cortical tissue of the motor area. The possibility of obtaining a cerebral sparing action by utilizing molecules devoid of anesthetic action is suggested.

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Metabolic Profiling of Hearts Exposed to Sevoflurane and Propofol Reveals Distinct Regulation of Fatty Acid and Glucose Oxidation

Anesthesiology ◽

10.1097/aln.0b013e3181e2c1a1 ◽

2010 ◽

Vol 113 (3) ◽

pp. 541-551 ◽

Cited By ~ 6

Author(s):

Lianguo Wang ◽

Kerry W. S. Ko ◽

Eliana Lucchinetti ◽

Liyan Zhang ◽

Heinz Troxler ◽

...

Keyword(s):

Fatty Acid ◽

Energy Metabolism ◽

Lipid Rafts ◽

Metabolic Profiling ◽

Glucose Oxidation ◽

Molecular Mechanisms ◽

Glucose Transporter ◽

Left Ventricular ◽

Glucose Transporter 4 ◽

Oxidative Energy Metabolism

Background Myocardial energy metabolism is a strong predictor of postoperative cardiac function. This study profiled the metabolites and metabolic changes in the myocardium exposed to sevoflurane, propofol, and Intralipid and investigated the underlying molecular mechanisms. Methods Sevoflurane (2 vol%) and propofol (10 and 100 microM) in the formulation of 1% Diprivan (AstraZeneca Inc., Mississauga, ON, Canada) were compared for their effects on oxidative energy metabolism and contractility in the isolated working rat heart model. Intralipid served as a control. Substrate flux through the major pathways for adenosine triphosphate generation in the heart, that is, fatty acid and glucose oxidation, was measured using [H]palmitate and [C]glucose. Biochemical analyses of nucleotides, acyl-CoAs, ceramides, and 32 acylcarnitine species were used to profile individual metabolites. Lipid rafts were isolated and used for Western blotting of the plasma membrane transporters CD36 and glucose transporter 4. Results Metabolic profiling of the hearts exposed to sevoflurane and propofol revealed distinct regulation of fatty acid and glucose oxidation. Sevoflurane selectively decreased fatty acid oxidation, which was closely related to a marked reduction in left ventricular work. In contrast, propofol at 100 microM but not 10 microM increased glucose oxidation without affecting cardiac work. Sevoflurane decreased fatty acid transporter CD36 in lipid rafts/caveolae, whereas high propofol increased pyruvate dehydrogenase activity without affecting glucose transporter 4, providing mechanisms for the fuel shifts in energy metabolism. Propofol increased ceramide formation, and Intralipid increased hydroxy acylcarnitine species. Conclusions Anesthetics and their solvents elicit distinct metabolic profiles in the myocardium, which may have clinical implications for the already jeopardized diseased heart.

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Responses in muscle sympathetic activity to acute hypoxia in humans

Journal of Applied Physiology ◽

10.1152/jappl.1988.65.4.1548 ◽

1988 ◽

Vol 65 (4) ◽

pp. 1548-1552 ◽

Cited By ~ 127

Author(s):

M. Saito ◽

T. Mano ◽

S. Iwase ◽

K. Koga ◽

H. Abe ◽

...

Keyword(s):

Sympathetic Activity ◽

Tibial Nerve ◽

Acute Hypoxia ◽

Total Activity ◽

Simulated Altitude ◽

Healthy Male ◽

Hypoxic Conditions ◽

Tungsten Microelectrode ◽

Burst Amplitude ◽

Male Subjects

Responses in muscle sympathetic activity (MSA) to acute hypoxia were studied in 13 healthy male subjects under hypobaric hypoxic conditions at a simulated altitude of 4,000, 5,000, and 6,000 m. Efferent postganglionic MSA was recorded directly with a tungsten microelectrode inserted percutaneously into the tibial nerve. Heart rate (HR) and respiratory rate (RR) were counted respectively from the R wave of an electrocardiogram and from the respiratory tracing recorded by the strain-gauge method. The average values of the MSA burst rate and total activity of MSA (burst rate x mean burst amplitude) at 4,000, 5,000, and 6,000 m were 36.4 +/- 2.6, 39.1 +/- 3.1, and 40.2 +/- 4.2 (SE) bursts/min and 616 +/- 138, 794 +/- 190, and 764 +/- 227 arbitrary units, respectively. These values were significantly higher than the values of 27.1 +/- 2.9 bursts/min and 446 +/- 28 at sea level. HR increased significantly at altitudes, but RR did not show significant change. Under severe hypoxic conditions beyond 5,000 m, there were large interindividual differences in the MSA responsiveness to hypoxia. The results indicate that MSA is activated under hypoxia by stimulating the chemoreceptors. However, the central controlling mechanisms that would be affected by hypoxia may also influence the MSA responsiveness under severe hypoxia.

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