Xanthine urolithiasis: Inhibitors of xanthine crystallization

Objective: To identify in vitro inhibitors of xanthine crystallization that have potential for inhibiting the formation of xanthine crystals in urine and preventing the development of the renal calculi in patients with xanthinuria. Methods: The formation of xanthine crystals in synthetic urine and t...

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Authors: Grases, Felix, Costa-Bauza, Antonia, Roig, Joan, Rodríguez, Adrián
Format: article
Publication Date:2018
Country:España
Institution:Instituto de Salud Carlos III (ISCIII)
Repository:Repisalud
Language:English
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/22606
Online Access:https://hdl.handle.net/20.500.12105/22606
Access Level:Open access
Keyword:Xantina
Xantinas
Aldehído Oxidasa
Regulación hacia Abajo
Errores Innatos del Metabolismo
Xantina Deshidrogenasa
Cristalización
Técnicas In Vitro
Cálculos Renales
Humanos
Urolitiasis
Errores Innatos del Metabolismo de la Purina-Pirimidina
Precipitación Química
Urolithiasis
In Vitro Techniques
Kidney Calculi
Aldehyde Oxidase
Humans
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Crystallization
Down-Regulation
Xanthine Dehydrogenase
Xanthines
Chemical Precipitation
Xanthine
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spelling Xanthine urolithiasis: Inhibitors of xanthine crystallizationGrases, FelixCosta-Bauza, AntoniaRoig, JoanRodríguez, AdriánXantinaXantinasAldehído OxidasaRegulación hacia AbajoErrores Innatos del MetabolismoXantina DeshidrogenasaCristalizaciónTécnicas In VitroCálculos RenalesHumanosUrolitiasisErrores Innatos del Metabolismo de la Purina-PirimidinaPrecipitación QuímicaUrolithiasisIn Vitro TechniquesKidney CalculiAldehyde OxidaseHumansPurine-Pyrimidine Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsCrystallizationDown-RegulationXanthine DehydrogenaseXanthinesChemical PrecipitationXanthineObjective: To identify in vitro inhibitors of xanthine crystallization that have potential for inhibiting the formation of xanthine crystals in urine and preventing the development of the renal calculi in patients with xanthinuria. Methods: The formation of xanthine crystals in synthetic urine and the effects of 10 potential crystallization inhibitors were assessed using a kinetic turbidimetric system with a photometer. The maximum concentration tested for each compound was: 20 mg/L for 3-methylxanthine (3MX); 40 mg/L for 7-methylxanthine (7-MX), 1-methylxanthine (1-MX), theobromine (TB), theophylline, paraxanthine, and caffeine; 45 mg/L for 1-methyluric acid; 80 mg/L for 1,3-dimethyluric acid; and 200 mg/L for hypoxanthine. Scanning electron microscopy was used to examine the morphology of the crystals formed when inhibitory effects were observed. Results: Only 7-MX, 3-MX, and 1-MX significantly inhibited xanthine crystallization at the tested concentrations. Mixtures of inhibitors had an additive effect rather than a synergistic effect on crystallization. Conclusion: Two of the inhibitors identified here D 7-MX and 3-MX D are major metabolites of TB. In particular, after TB consumption, 20% is excreted in the urine as TB, 21.5% as 3-MX, and 36% as 7-MX. Thus, consumption of theobromine could protect patients with xanthinuria from the development of renal xanthine calculi. Clinical trials are necessary to demonstrate these effects in vivo.Public Library of Science (PLOS)20242024-09-0620182018-08-2920182018-08-29research articlehttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articlehttps://hdl.handle.net/20.500.12105/22606reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/226062026-06-12T12:43:37Z
dc.title.none.fl_str_mv Xanthine urolithiasis: Inhibitors of xanthine crystallization
title Xanthine urolithiasis: Inhibitors of xanthine crystallization
spellingShingle Xanthine urolithiasis: Inhibitors of xanthine crystallization
Grases, Felix
Xantina
Xantinas
Aldehído Oxidasa
Regulación hacia Abajo
Errores Innatos del Metabolismo
Xantina Deshidrogenasa
Cristalización
Técnicas In Vitro
Cálculos Renales
Humanos
Urolitiasis
Errores Innatos del Metabolismo de la Purina-Pirimidina
Precipitación Química
Urolithiasis
In Vitro Techniques
Kidney Calculi
Aldehyde Oxidase
Humans
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Crystallization
Down-Regulation
Xanthine Dehydrogenase
Xanthines
Chemical Precipitation
Xanthine
title_short Xanthine urolithiasis: Inhibitors of xanthine crystallization
title_full Xanthine urolithiasis: Inhibitors of xanthine crystallization
title_fullStr Xanthine urolithiasis: Inhibitors of xanthine crystallization
title_full_unstemmed Xanthine urolithiasis: Inhibitors of xanthine crystallization
title_sort Xanthine urolithiasis: Inhibitors of xanthine crystallization
dc.creator.none.fl_str_mv Grases, Felix
Costa-Bauza, Antonia
Roig, Joan
Rodríguez, Adrián
author Grases, Felix
author_facet Grases, Felix
Costa-Bauza, Antonia
Roig, Joan
Rodríguez, Adrián
author_role author
author2 Costa-Bauza, Antonia
Roig, Joan
Rodríguez, Adrián
author2_role author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Xantina
Xantinas
Aldehído Oxidasa
Regulación hacia Abajo
Errores Innatos del Metabolismo
Xantina Deshidrogenasa
Cristalización
Técnicas In Vitro
Cálculos Renales
Humanos
Urolitiasis
Errores Innatos del Metabolismo de la Purina-Pirimidina
Precipitación Química
Urolithiasis
In Vitro Techniques
Kidney Calculi
Aldehyde Oxidase
Humans
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Crystallization
Down-Regulation
Xanthine Dehydrogenase
Xanthines
Chemical Precipitation
Xanthine
topic Xantina
Xantinas
Aldehído Oxidasa
Regulación hacia Abajo
Errores Innatos del Metabolismo
Xantina Deshidrogenasa
Cristalización
Técnicas In Vitro
Cálculos Renales
Humanos
Urolitiasis
Errores Innatos del Metabolismo de la Purina-Pirimidina
Precipitación Química
Urolithiasis
In Vitro Techniques
Kidney Calculi
Aldehyde Oxidase
Humans
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Crystallization
Down-Regulation
Xanthine Dehydrogenase
Xanthines
Chemical Precipitation
Xanthine
description Objective: To identify in vitro inhibitors of xanthine crystallization that have potential for inhibiting the formation of xanthine crystals in urine and preventing the development of the renal calculi in patients with xanthinuria. Methods: The formation of xanthine crystals in synthetic urine and the effects of 10 potential crystallization inhibitors were assessed using a kinetic turbidimetric system with a photometer. The maximum concentration tested for each compound was: 20 mg/L for 3-methylxanthine (3MX); 40 mg/L for 7-methylxanthine (7-MX), 1-methylxanthine (1-MX), theobromine (TB), theophylline, paraxanthine, and caffeine; 45 mg/L for 1-methyluric acid; 80 mg/L for 1,3-dimethyluric acid; and 200 mg/L for hypoxanthine. Scanning electron microscopy was used to examine the morphology of the crystals formed when inhibitory effects were observed. Results: Only 7-MX, 3-MX, and 1-MX significantly inhibited xanthine crystallization at the tested concentrations. Mixtures of inhibitors had an additive effect rather than a synergistic effect on crystallization. Conclusion: Two of the inhibitors identified here D 7-MX and 3-MX D are major metabolites of TB. In particular, after TB consumption, 20% is excreted in the urine as TB, 21.5% as 3-MX, and 36% as 7-MX. Thus, consumption of theobromine could protect patients with xanthinuria from the development of renal xanthine calculi. Clinical trials are necessary to demonstrate these effects in vivo.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-08-29
2018
2018-08-29
2024
2024-09-06
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/20.500.12105/22606
url https://hdl.handle.net/20.500.12105/22606
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
Attribution 4.0 International
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
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science (PLOS)
publisher.none.fl_str_mv Public Library of Science (PLOS)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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