7-Methylxanthine Inhibits the Formation of Monosodium Urate Crystals by Increasing Its Solubility

Gout is characterized by the formation of monosodium urate crystals in peripheral joints. We carried out laboratory studies to investigate the effect of adding nine different methylxanthines and two different methylated uric acid derivatives on the development of these crystals over the course of 96...

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Detalles Bibliográficos
Autores: Costa-Bauzà, Antonia, Grases, Fèlix
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:inglés
OAI Identifier:oai:docusalut.com:20.500.13003/20140
Acceso en línea:https://hdl.handle.net/20.500.13003/20140
Access Level:acceso abierto
Palabra clave:Uric Acid
Solubility
Theobromine
Caffeine
Cafeína
Solubilidad
Ácido Úrico
Teobromina
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spelling 7-Methylxanthine Inhibits the Formation of Monosodium Urate Crystals by Increasing Its SolubilityCosta-Bauzà, AntoniaGrases, FèlixUric AcidSolubilityTheobromineCaffeineCafeínaSolubilidadÁcido ÚricoTeobrominaGout is characterized by the formation of monosodium urate crystals in peripheral joints. We carried out laboratory studies to investigate the effect of adding nine different methylxanthines and two different methylated uric acid derivatives on the development of these crystals over the course of 96 h in a medium whose composition was similar to that of synovial fluid. Our results showed that 7-methylxanthine reduced or totally prevented crystal formation; 1-methylxanthine, 3-methylxanthine, 7-methyluric acid, and 1,3-dimethyluric acid had weaker effects, and the other molecules had no apparent effect. The presented results indicate that a 7-methylxanthine concentration of about 6 × 10-5 M (10 mg/L) prevented the formation of crystals for an initial urate concentration of 1.78 × 10-3 M (300 mg/L) in the presence of 0.4 M of Na+ for 96 h at 25 °C and a pH of 7.4. We attribute these results to alterations in thermodynamics, not kinetics. Our results suggest that prevention of crystallization in vivo could be achieved by direct oral administration of 7-methylxanthine or other methylxanthines that are metabolized to 7-methylxanthine. For example, the hepatic metabolism of theobromine leads to significant plasma levels of 7-methylxanthine (14% of the initial theobromine concentration) and 3-methylxanthine (6% of the initial theobromine concentration); however, 7-methyluric acid is present at very low concentrations in the plasma. It is important to consider that several of the specific molecules we examined (theobromine, caffeine, theophylline, dyphylline, etophylline, and pentoxifylline) did not directly affect crystallization.20232023-12-1020232023-12-10research articlehttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.13003/20140reponame:Docusalutinstname:Conselleria de Salut i Consum del Govern de les Illes BalearsInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docusalut.com:20.500.13003/201402026-06-22T12:44:07Z
dc.title.none.fl_str_mv 7-Methylxanthine Inhibits the Formation of Monosodium Urate Crystals by Increasing Its Solubility
title 7-Methylxanthine Inhibits the Formation of Monosodium Urate Crystals by Increasing Its Solubility
spellingShingle 7-Methylxanthine Inhibits the Formation of Monosodium Urate Crystals by Increasing Its Solubility
Costa-Bauzà, Antonia
Uric Acid
Solubility
Theobromine
Caffeine
Cafeína
Solubilidad
Ácido Úrico
Teobromina
title_short 7-Methylxanthine Inhibits the Formation of Monosodium Urate Crystals by Increasing Its Solubility
title_full 7-Methylxanthine Inhibits the Formation of Monosodium Urate Crystals by Increasing Its Solubility
title_fullStr 7-Methylxanthine Inhibits the Formation of Monosodium Urate Crystals by Increasing Its Solubility
title_full_unstemmed 7-Methylxanthine Inhibits the Formation of Monosodium Urate Crystals by Increasing Its Solubility
title_sort 7-Methylxanthine Inhibits the Formation of Monosodium Urate Crystals by Increasing Its Solubility
dc.creator.none.fl_str_mv Costa-Bauzà, Antonia
Grases, Fèlix
author Costa-Bauzà, Antonia
author_facet Costa-Bauzà, Antonia
Grases, Fèlix
author_role author
author2 Grases, Fèlix
author2_role author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Uric Acid
Solubility
Theobromine
Caffeine
Cafeína
Solubilidad
Ácido Úrico
Teobromina
topic Uric Acid
Solubility
Theobromine
Caffeine
Cafeína
Solubilidad
Ácido Úrico
Teobromina
description Gout is characterized by the formation of monosodium urate crystals in peripheral joints. We carried out laboratory studies to investigate the effect of adding nine different methylxanthines and two different methylated uric acid derivatives on the development of these crystals over the course of 96 h in a medium whose composition was similar to that of synovial fluid. Our results showed that 7-methylxanthine reduced or totally prevented crystal formation; 1-methylxanthine, 3-methylxanthine, 7-methyluric acid, and 1,3-dimethyluric acid had weaker effects, and the other molecules had no apparent effect. The presented results indicate that a 7-methylxanthine concentration of about 6 × 10-5 M (10 mg/L) prevented the formation of crystals for an initial urate concentration of 1.78 × 10-3 M (300 mg/L) in the presence of 0.4 M of Na+ for 96 h at 25 °C and a pH of 7.4. We attribute these results to alterations in thermodynamics, not kinetics. Our results suggest that prevention of crystallization in vivo could be achieved by direct oral administration of 7-methylxanthine or other methylxanthines that are metabolized to 7-methylxanthine. For example, the hepatic metabolism of theobromine leads to significant plasma levels of 7-methylxanthine (14% of the initial theobromine concentration) and 3-methylxanthine (6% of the initial theobromine concentration); however, 7-methyluric acid is present at very low concentrations in the plasma. It is important to consider that several of the specific molecules we examined (theobromine, caffeine, theophylline, dyphylline, etophylline, and pentoxifylline) did not directly affect crystallization.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-12-10
2023
2023-12-10
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.13003/20140
url https://hdl.handle.net/20.500.13003/20140
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Docusalut
instname:Conselleria de Salut i Consum del Govern de les Illes Balears
instname_str Conselleria de Salut i Consum del Govern de les Illes Balears
reponame_str Docusalut
collection Docusalut
repository.name.fl_str_mv
repository.mail.fl_str_mv
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