{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T11:28:06Z","timestamp":1768476486920,"version":"3.49.0"},"reference-count":33,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,10]],"date-time":"2023-12-10T00:00:00Z","timestamp":1702166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n, Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["PID2019-104331RB-I00"],"award-info":[{"award-number":["PID2019-104331RB-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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 \u00d7 10\u22125 M (10 mg\/L) prevented the formation of crystals for an initial urate concentration of 1.78 \u00d7 10\u22123 M (300 mg\/L) in the presence of 0.4 M of Na+ for 96 h at 25 \u00b0C 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.<\/jats:p>","DOI":"10.3390\/biom13121769","type":"journal-article","created":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T06:56:00Z","timestamp":1702277760000},"page":"1769","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["7-Methylxanthine Inhibits the Formation of Monosodium Urate Crystals by Increasing Its Solubility"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0647-4154","authenticated-orcid":false,"given":"Antonia","family":"Costa-Bauza","sequence":"first","affiliation":[{"name":"Laboratory of Renal Lithiasis Research, University Institute of Health Science Research (IUNICS-IdISBa), University of Balearic Islands, Ctra. de Valldemossa km 7.5, 07122 Palma, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5636-9139","authenticated-orcid":false,"given":"Felix","family":"Grases","sequence":"additional","affiliation":[{"name":"Laboratory of Renal Lithiasis Research, University Institute of Health Science Research (IUNICS-IdISBa), University of Balearic Islands, Ctra. de Valldemossa km 7.5, 07122 Palma, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1136\/bmj.2.4737.947","article-title":"Uric-acid levels in blood and plasma","volume":"2","author":"Archer","year":"1951","journal-title":"Br. 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