Cargando…
Methylxanthines Inhibit Primary Amine Oxidase and Monoamine Oxidase Activities of Human Adipose Tissue
Background: Methylxanthines including caffeine and theobromine are widely consumed compounds and were recently shown to interact with bovine copper-containing amine oxidase. To the best of our knowledge, no direct demonstration of any interplay between these phytochemicals and human primary amine ox...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235778/ https://www.ncbi.nlm.nih.gov/pubmed/32252407 http://dx.doi.org/10.3390/medicines7040018 |
_version_ | 1783536033719123968 |
---|---|
author | Haj Ahmed, Wiem Peiro, Cécile Fontaine, Jessica Ryan, Barry J. Kinsella, Gemma K. O’Sullivan, Jeff Grolleau, Jean-Louis Henehan, Gary T.M. Carpéné, Christian |
author_facet | Haj Ahmed, Wiem Peiro, Cécile Fontaine, Jessica Ryan, Barry J. Kinsella, Gemma K. O’Sullivan, Jeff Grolleau, Jean-Louis Henehan, Gary T.M. Carpéné, Christian |
author_sort | Haj Ahmed, Wiem |
collection | PubMed |
description | Background: Methylxanthines including caffeine and theobromine are widely consumed compounds and were recently shown to interact with bovine copper-containing amine oxidase. To the best of our knowledge, no direct demonstration of any interplay between these phytochemicals and human primary amine oxidase (PrAO) has been reported to date. We took advantage of the coexistence of PrAO and monoamine oxidase (MAO) activities in human subcutaneous adipose tissue (hScAT) to test the interaction between several methylxanthines and these enzymes, which are involved in many key pathophysiological processes. Methods: Benzylamine, methylamine, and tyramine were used as substrates for PrAO and MAO in homogenates of subcutaneous adipose depots obtained from overweight women undergoing plastic surgery. Methylxanthines were tested as substrates or inhibitors by fluorimetric determination of hydrogen peroxide, an end-product of amine oxidation. Results: Semicarbazide-sensitive PrAO activity was inhibited by theobromine, caffeine, and isobutylmethylxanthine (IBMX) while theophylline, paraxanthine, and 7-methylxanthine had little effect. Theobromine inhibited PrAO activity by 54% at 2.5 mM. Overall, the relationship between methylxanthine structure and the degree of inhibition was similar to that seen with bovine PrAO, although higher concentrations (mM) were required for inhibition. Theobromine also inhibited oxidation of tyramine by MAO, at the limits of its solubility in a DMSO vehicle. At doses higher than 12 % v/v, DMSO impaired MAO activity. MAO was also inhibited by millimolar doses of IBMX, caffeine and by other methylxanthines to a lesser extent. Conclusions: This preclinical study extrapolates previous findings with bovine PrAO to human tissues. Given that PrAO is a potential target for anti-inflammatory drugs, it indicates that alongside phosphodiesterase inhibition and adenosine receptor antagonism, PrAO and MAO inhibition could contribute to the health benefits of methylxanthines, especially their anti-inflammatory effects. |
format | Online Article Text |
id | pubmed-7235778 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72357782020-05-22 Methylxanthines Inhibit Primary Amine Oxidase and Monoamine Oxidase Activities of Human Adipose Tissue Haj Ahmed, Wiem Peiro, Cécile Fontaine, Jessica Ryan, Barry J. Kinsella, Gemma K. O’Sullivan, Jeff Grolleau, Jean-Louis Henehan, Gary T.M. Carpéné, Christian Medicines (Basel) Article Background: Methylxanthines including caffeine and theobromine are widely consumed compounds and were recently shown to interact with bovine copper-containing amine oxidase. To the best of our knowledge, no direct demonstration of any interplay between these phytochemicals and human primary amine oxidase (PrAO) has been reported to date. We took advantage of the coexistence of PrAO and monoamine oxidase (MAO) activities in human subcutaneous adipose tissue (hScAT) to test the interaction between several methylxanthines and these enzymes, which are involved in many key pathophysiological processes. Methods: Benzylamine, methylamine, and tyramine were used as substrates for PrAO and MAO in homogenates of subcutaneous adipose depots obtained from overweight women undergoing plastic surgery. Methylxanthines were tested as substrates or inhibitors by fluorimetric determination of hydrogen peroxide, an end-product of amine oxidation. Results: Semicarbazide-sensitive PrAO activity was inhibited by theobromine, caffeine, and isobutylmethylxanthine (IBMX) while theophylline, paraxanthine, and 7-methylxanthine had little effect. Theobromine inhibited PrAO activity by 54% at 2.5 mM. Overall, the relationship between methylxanthine structure and the degree of inhibition was similar to that seen with bovine PrAO, although higher concentrations (mM) were required for inhibition. Theobromine also inhibited oxidation of tyramine by MAO, at the limits of its solubility in a DMSO vehicle. At doses higher than 12 % v/v, DMSO impaired MAO activity. MAO was also inhibited by millimolar doses of IBMX, caffeine and by other methylxanthines to a lesser extent. Conclusions: This preclinical study extrapolates previous findings with bovine PrAO to human tissues. Given that PrAO is a potential target for anti-inflammatory drugs, it indicates that alongside phosphodiesterase inhibition and adenosine receptor antagonism, PrAO and MAO inhibition could contribute to the health benefits of methylxanthines, especially their anti-inflammatory effects. MDPI 2020-04-02 /pmc/articles/PMC7235778/ /pubmed/32252407 http://dx.doi.org/10.3390/medicines7040018 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Haj Ahmed, Wiem Peiro, Cécile Fontaine, Jessica Ryan, Barry J. Kinsella, Gemma K. O’Sullivan, Jeff Grolleau, Jean-Louis Henehan, Gary T.M. Carpéné, Christian Methylxanthines Inhibit Primary Amine Oxidase and Monoamine Oxidase Activities of Human Adipose Tissue |
title | Methylxanthines Inhibit Primary Amine Oxidase and Monoamine Oxidase Activities of Human Adipose Tissue |
title_full | Methylxanthines Inhibit Primary Amine Oxidase and Monoamine Oxidase Activities of Human Adipose Tissue |
title_fullStr | Methylxanthines Inhibit Primary Amine Oxidase and Monoamine Oxidase Activities of Human Adipose Tissue |
title_full_unstemmed | Methylxanthines Inhibit Primary Amine Oxidase and Monoamine Oxidase Activities of Human Adipose Tissue |
title_short | Methylxanthines Inhibit Primary Amine Oxidase and Monoamine Oxidase Activities of Human Adipose Tissue |
title_sort | methylxanthines inhibit primary amine oxidase and monoamine oxidase activities of human adipose tissue |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235778/ https://www.ncbi.nlm.nih.gov/pubmed/32252407 http://dx.doi.org/10.3390/medicines7040018 |
work_keys_str_mv | AT hajahmedwiem methylxanthinesinhibitprimaryamineoxidaseandmonoamineoxidaseactivitiesofhumanadiposetissue AT peirocecile methylxanthinesinhibitprimaryamineoxidaseandmonoamineoxidaseactivitiesofhumanadiposetissue AT fontainejessica methylxanthinesinhibitprimaryamineoxidaseandmonoamineoxidaseactivitiesofhumanadiposetissue AT ryanbarryj methylxanthinesinhibitprimaryamineoxidaseandmonoamineoxidaseactivitiesofhumanadiposetissue AT kinsellagemmak methylxanthinesinhibitprimaryamineoxidaseandmonoamineoxidaseactivitiesofhumanadiposetissue AT osullivanjeff methylxanthinesinhibitprimaryamineoxidaseandmonoamineoxidaseactivitiesofhumanadiposetissue AT grolleaujeanlouis methylxanthinesinhibitprimaryamineoxidaseandmonoamineoxidaseactivitiesofhumanadiposetissue AT henehangarytm methylxanthinesinhibitprimaryamineoxidaseandmonoamineoxidaseactivitiesofhumanadiposetissue AT carpenechristian methylxanthinesinhibitprimaryamineoxidaseandmonoamineoxidaseactivitiesofhumanadiposetissue |