Abstract | OBJECTIVES: 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. METHODS: RESULTS: 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. CONCLUSION: 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.
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Authors | Lisa K Stamp, Rufus Turner, Irada S Khalilova, Mei Zhang, Jill Drake, Louisa V Forbes, Anthony J Kettle |
Journal | Rheumatology (Oxford, England)
(Rheumatology (Oxford))
Vol. 53
Issue 11
Pg. 1958-65
(Nov 2014)
ISSN: 1462-0332 [Electronic] England |
PMID | 24899662
(Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected]. |
Chemical References |
- Gout Suppressants
- Uric Acid
- Allopurinol
- Peroxidase
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Allopurinol
(therapeutic use)
- Enzyme-Linked Immunosorbent Assay
- Female
- Gout
(drug therapy, etiology, metabolism)
- Gout Suppressants
(therapeutic use)
- Humans
- Hyperuricemia
(blood, complications)
- Male
- Mass Spectrometry
- Middle Aged
- Oxidation-Reduction
- Oxidative Stress
- Peroxidase
(blood)
- Uric Acid
(blood)
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