Efficacy of Theobromine and Its Metabolites in Reducing the Risk of Uric Acid Lithiasis

Costa-Bauzà, Antònia; Calvó, Paula; Hernández, Yumaira; Gráses, F.

doi:10.3390/ijms241310879

Cited by 4 publications

(1 citation statement)

References 27 publications

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“…Nevertheless, theobromine also acts as an inhibitor of UA crystallization through interaction with its crystals, which leads to the UA crystals formed having a different morphology in its presence than in its absence [9]. Moreover, theobromine and some of its metabolites (methylxanthines which lacked a substituent at position 1) contribute globally to reducing the risk of UA stones [10]. In this sense, it has been shown that the consumption of cocoa-derived products, which are rich in theobromine, reduces the risk of crystallization of UA in urine [11,12].…”

Section: Introductionmentioning

confidence: 99%

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

Costa-Bauza,

Grases

2023

Biomolecules

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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.

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Section: Introductionmentioning

confidence: 99%