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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Detalles Bibliográficos
Autores: Grases, Felix, Costa-Bauza, Antonia, Roig, Joan, Rodríguez, Adrián
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/22606
Acceso en línea:https://hdl.handle.net/20.500.12105/22606
Access Level:acceso abierto
Palabra clave: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
Descripción
Sumario: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.