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Myeloperoxidase and oxidation of uric acid in gout: implications for the clinical consequences of hyperuricaemia.

Rheumatology (Oxford, England) (2014-06-06)
Lisa K Stamp, Rufus Turner, Irada S Khalilova, Mei Zhang, Jill Drake, Louisa V Forbes, Anthony J Kettle
ABSTRACT

The aims of this study were to establish whether, in patients with gout, MPO is released from neutrophils and urate is oxidized to allantoin and if these effects are attenuated by allopurinol. MPO, urate, allantoin and oxypurinol were measured in plasma from 54 patients with gout and 27 healthy controls. Twenty-three patients had acute gout, 13 of whom were receiving allopurinol, and 31 had intercritical gout, 20 of whom were receiving allopurinol. Ten additional gout patients had samples collected before and after 4 weeks of allopurinol. Plasma MPO and its specific activity were higher (P < 0.05) in patients with acute gout not receiving allopurinol compared with controls. MPO protein in patients' plasma was related to urate concentration (r = 0.5, P < 0.001). Plasma allantoin was higher (P < 0.001) in all patient groups compared with controls. In controls and patients not receiving allopurinol, allantoin was associated with plasma urate (r = 0.62, P < 0.001) and MPO activity (r = 0.45, P < 0.002). When 10 patients were treated with allopurinol, it lowered their plasma urate and allantoin (P = 0.002). In all patients receiving allopurinol, plasma allantoin was related to oxypurinol (r = 0.65, P < 0.0001). Oxypurinol was a substrate for purified MPO that enhanced the oxidation of urate. Increased concentrations of urate in gout lead to the release of MPO from neutrophils and the oxidation of urate. Products of MPO and reactive metabolites of urate may contribute to the pathology of gout and hyperuricaemia. At low concentrations, oxypurinol should reduce inflammation, but high concentrations may contribute to oxidative stress.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Xanthine, ≥99%
Sigma-Aldrich
Allopurinol, xanthine oxidase inhibitor
Sigma-Aldrich
Xanthine, ≥99.5% (HPLC), purified by recrystallization
Supelco
Allopurinol, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Xanthine, BioUltra, ≥99%
Sigma-Aldrich
Oxypurinol, ≥98% (HPLC)
Allopurinol, European Pharmacopoeia (EP) Reference Standard
USP
Allopurinol, United States Pharmacopeia (USP) Reference Standard
Supelco
Oxypurinol, analytical standard