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Increased hyperpolarized [1‐(13)C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized (13)C‐labelled bicarbonate

Arthritic conditions are a major source of chronic pain. Furthering our understanding of disease mechanisms creates the opportunity to develop more targeted therapeutics. In rheumatoid arthritis (RA), measurements of pH in human synovial fluid suggest that acidosis occurs, but that this is highly va...

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Autores principales: Wright, Alan J., Husson, Zoé M.A., Hu, De‐En, Callejo, Gerard, Brindle, Kevin M., Smith, Ewan St. John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887936/
https://www.ncbi.nlm.nih.gov/pubmed/29380927
http://dx.doi.org/10.1002/nbm.3892
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author Wright, Alan J.
Husson, Zoé M.A.
Hu, De‐En
Callejo, Gerard
Brindle, Kevin M.
Smith, Ewan St. John
author_facet Wright, Alan J.
Husson, Zoé M.A.
Hu, De‐En
Callejo, Gerard
Brindle, Kevin M.
Smith, Ewan St. John
author_sort Wright, Alan J.
collection PubMed
description Arthritic conditions are a major source of chronic pain. Furthering our understanding of disease mechanisms creates the opportunity to develop more targeted therapeutics. In rheumatoid arthritis (RA), measurements of pH in human synovial fluid suggest that acidosis occurs, but that this is highly variable between individuals. Here we sought to determine if tissue acidosis occurs in a widely used rodent arthritis model: complete Freund's adjuvant (CFA)‐induced inflammation. CFA robustly evoked paw and ankle swelling, concomitant with worsening clinical scores over time. We used magnetic resonance spectroscopic imaging of hyperpolarized [1‐(13)C]pyruvate metabolism to demonstrate that CFA induces an increase in the lactate‐to‐pyruvate ratio. This increase is indicative of enhanced glycolysis and an increased lactate concentration, as has been observed in the synovial fluid from RA patients, and which was correlated with acidosis. We also measured the (13)CO(2)/H(13)CO(3) (−) ratio, in animals injected with hyperpolarized H(13)CO(3) (−), to estimate extracellular tissue pH and showed that despite the apparent increase in glycolytic activity in CFA‐induced inflammation there was no accompanying decrease in extracellular pH. The pH was 7.23 ± 0.06 in control paws and 7.32 ± 0.09 in inflamed paws. These results could explain why mice lacking acid‐sensing ion channel subunits 1, 2 and 3 do not display any changes in mechanical or thermal hyperalgesia in CFA‐induced inflammation.
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spelling pubmed-58879362018-04-12 Increased hyperpolarized [1‐(13)C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized (13)C‐labelled bicarbonate Wright, Alan J. Husson, Zoé M.A. Hu, De‐En Callejo, Gerard Brindle, Kevin M. Smith, Ewan St. John NMR Biomed Research Articles Arthritic conditions are a major source of chronic pain. Furthering our understanding of disease mechanisms creates the opportunity to develop more targeted therapeutics. In rheumatoid arthritis (RA), measurements of pH in human synovial fluid suggest that acidosis occurs, but that this is highly variable between individuals. Here we sought to determine if tissue acidosis occurs in a widely used rodent arthritis model: complete Freund's adjuvant (CFA)‐induced inflammation. CFA robustly evoked paw and ankle swelling, concomitant with worsening clinical scores over time. We used magnetic resonance spectroscopic imaging of hyperpolarized [1‐(13)C]pyruvate metabolism to demonstrate that CFA induces an increase in the lactate‐to‐pyruvate ratio. This increase is indicative of enhanced glycolysis and an increased lactate concentration, as has been observed in the synovial fluid from RA patients, and which was correlated with acidosis. We also measured the (13)CO(2)/H(13)CO(3) (−) ratio, in animals injected with hyperpolarized H(13)CO(3) (−), to estimate extracellular tissue pH and showed that despite the apparent increase in glycolytic activity in CFA‐induced inflammation there was no accompanying decrease in extracellular pH. The pH was 7.23 ± 0.06 in control paws and 7.32 ± 0.09 in inflamed paws. These results could explain why mice lacking acid‐sensing ion channel subunits 1, 2 and 3 do not display any changes in mechanical or thermal hyperalgesia in CFA‐induced inflammation. John Wiley and Sons Inc. 2018-01-30 2018-04 /pmc/articles/PMC5887936/ /pubmed/29380927 http://dx.doi.org/10.1002/nbm.3892 Text en © 2018 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Wright, Alan J.
Husson, Zoé M.A.
Hu, De‐En
Callejo, Gerard
Brindle, Kevin M.
Smith, Ewan St. John
Increased hyperpolarized [1‐(13)C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized (13)C‐labelled bicarbonate
title Increased hyperpolarized [1‐(13)C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized (13)C‐labelled bicarbonate
title_full Increased hyperpolarized [1‐(13)C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized (13)C‐labelled bicarbonate
title_fullStr Increased hyperpolarized [1‐(13)C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized (13)C‐labelled bicarbonate
title_full_unstemmed Increased hyperpolarized [1‐(13)C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized (13)C‐labelled bicarbonate
title_short Increased hyperpolarized [1‐(13)C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized (13)C‐labelled bicarbonate
title_sort increased hyperpolarized [1‐(13)c] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized (13)c‐labelled bicarbonate
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887936/
https://www.ncbi.nlm.nih.gov/pubmed/29380927
http://dx.doi.org/10.1002/nbm.3892
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