| Inactivation of xanthine oxidoreductase is associated with increased joint swelling and nitrotyrosine formation in acute antigen-induced arthritis. | |
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MedLine Citation:
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PMID: 15971422 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Arthritis is associated with increased articular formation of nitrotyrosine, which may contribute to injury. Nitrotyrosine is formed by nitration of tyrosine by reactive nitrogen species such as peroxynitrite, the formation of which may be enhanced by xanthine oxidoreductase (XOR), since it can generate nitric oxide from nitrite/nitrate, and superoxide during xanthine metabolism. We hypothesized that inactivation of XOR would protect against antigen-induced arthritis (AIA) and decrease nitrotyrosine formation. METHODS: AIA was induced with methylated bovine serum albumin (mBSA) in three groups of Wistar rats: animals fed on (1) tungsten-enriched chow (0.7 g/kg) (TG), which inactivates XOR, (2) standard chow (SG), and (3) rats treated with allopurinol (50 mg/kg/day; p.o.) (AG). Nitrotyrosine in patella-synovium was quantified by mass spectrometry three weeks after intra-articular (i.a.) antigen injection. RESULTS: Treatment with tungsten, but not allopurinol, suppressed plasma and articular XOR activity at < or = 0.9% of normal levels. XOR inactivation was associated with increased knee swelling 24-48 hrs post i.a. mBSA, compared with controls (mean increase +/- SEM of knee diameter from baseline of 3.3 +/- 0.5, 2.0 +/- 0.3 and 1.9 +/- 0.2 mm in TG, SG and AG (n = 14 each group), respectively; p < 0.05, TG vs SG, ANOVA). Mean ratio of articular nitrotyrosine-tyrosine (+/- SEM) was increased in the XOR-inactivated group, compared with controls: 12.3 +/- 0.7, 9.6 +/- 0.8 and 10.4 +/- 0.5 pg/microg in TG, SG and AG, respectively; p < 0.05, TG vs SG. CONCLUSION: Contrary to expectation, XOR inactivation was associated with increased joint swelling and articular tyrosine nitration in acute AIA, suggesting a novel, protective role for XOR in inflammatory arthritis. |
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Authors:
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R Klocke; A R Mani; K P Moore; D R Blake; P I Mapp |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Clinical and experimental rheumatology Volume: 23 ISSN: 0392-856X ISO Abbreviation: Clin. Exp. Rheumatol. Publication Date: 2005 May-Jun |
Date Detail:
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Created Date: 2005-06-23 Completed Date: 2005-08-23 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8308521 Medline TA: Clin Exp Rheumatol Country: Italy |
Other Details:
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Languages: eng Pagination: 345-50 Citation Subset: IM |
Affiliation:
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Department of Pharmacy & Pharmacology/Schoolfor Health, University of Bath, UK. Rainer.Klocke@dgoh.nhs.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Allopurinol
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therapeutic use Animals Arthritis, Experimental / drug therapy, enzymology*, pathology Cattle Enzyme Inhibitors / therapeutic use Joints / enzymology*, pathology Male Rats Rats, Wistar Serum Albumin, Bovine / administration & dosage Stifle / drug effects, pathology, radiography Synovial Membrane / drug effects, enzymology, pathology Tungsten / therapeutic use Tyrosine / analogs & derivatives*, metabolism* Xanthine Dehydrogenase / antagonists & inhibitors*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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//Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Serum Albumin, Bovine; 315-30-0/Allopurinol; 3604-79-3/3-nitrotyrosine; 55520-40-6/Tyrosine; 7440-33-7/Tungsten; EC 1.17.1.4/Xanthine Dehydrogenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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