Superoxide production by polymorphonuclear leucocytes in rheumatoid arthritis and osteoarthritis: in vivo inhibition by the antirheumatic drug piroxicam due to interference with the activation of the NADPH-oxidase.
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The superoxide (O2-) production of stimulated polymorphonuclear leucocytes is increased in patients with rheumatoid arthritis and osteoarthritis compared with controls. Treatment of these different groups with pharmacological amounts of the non-steroidal anti-inflammatory drug piroxicam in vivo resulted in a decrease of about 25% in O2- secretion by isolated granulocytes. In vitro experiments showed that piroxicam inhibits O2- production of granulocytes by interference with the stimulation of the NADPH-oxidase. Piroxicam caused diminished O2- production of membrane fragments if it was present during the stimulation of the NADPH-oxidase of the intact cells. During the actual O2- production of the stimulated membrane fragments piroxicam had no effect. It is concluded that piroxicam is able to inhibit granulocyte O2- production by blocking the activation of NADPH-oxidase, which results in diminished tissue destruction by oxygen free radicals in inflammatory diseases.
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A mechanism in RA involves elevated superoxide liberating free iron from ferritin in synovial fluid, thereby catalysing further damaging production of hydroxyl radicals.
“a mechanism [1256-1259] in which elevated superoxide liberates free iron from ferritin in synovial fluid (and elsewhere [1260]), thereby catalysing further the damaging production of hydroxyl radicals.”
From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [1258]
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- Authors
- Biemond, P., Swaak, A. J., Penders, J. M., Beindorff, C. M., & Koster, J. F.
- Affiliations
- Pfizer (Netherlands) (NL)
- Venue
- Annals of the Rheumatic Diseases
- Publisher
- Elsevier BV
- Published
- 1986-03
- Volume
- 45
- Issue
- 3
- Pages
- 249-255
- ISSN
- 0003-4967 (ISSN-L)
- PMC
- PMC1001859
- OpenAlex
- W2096842762
- Cited by
- 108
- References
- 23
- Citations by year
- 2022: 1 · 2021: 1 · 2019: 2 · 2018: 1 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 1 · 2012: 2
- FWCI
- 2.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annals of the Rheumatic Diseases (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- superoxide production, polymorphonuclear leukocytes, granulocytes, rheumatoid arthritis, osteoarthritis, piroxicam, NADPH oxidase, nonsteroidal anti-inflammatory drugs, oxygen free radicals, oxidative tissue damage
- MeSH terms
- Arthritis, Arthritis, Rheumatoid, Humans, NADH, NADPH Oxidoreductases, Neutrophils, Osteoarthritis, Piroxicam, Superoxides, Tetradecanoylphorbol Acetate, Thiazines, NADPH Oxidases
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