Abstract
Iron is an important catalyst of oxidative radical reactions and promotes the formation of the hydroxyl radical from the superoxide anion radical and hydrogen peroxide. The stimulatory effect of the hydroxyl radical on lipid peroxidation prompted the speculation that free iron may directly promote inflammation and that iron chelating agents may have useful anti-inflammatory properties. This hypothesis is tested in animal models of inflammation with a specific iron chelating agent, desferrioxamine. At low doses (6 . 6 mg/kg) intraperitoneal desferrioxamine stimulated the induction of acute foot pad swelling in rats by monosodium urate but at higher doses (above 200 mg/kg) it suppressed this inflammatory reaction. A similar anti-inflammatory effect was observed in carrageenan-induced foot pad swelling. In guinea-pigs in which a Glynn-Dumonde synovitis was induced with bovine gammaglobulin, desferrioxamine (100 mg/kg) stimulated the acute inflammatory induction phase of this chronic allergic monoarthritis model. Repeated administration of desferrioxamine (100 mg/kg) from the seventh to the twelfth day after intra-articular challenge with bovine gammaglobulin markedly depressed the chronic inflammatory phase. In-vitro experiments suggest that desferrioxamine inhibits iron-catalysed lipid peroxidation when it is poorly saturated with iron, but loses this effect when it is iron saturated. Such an effect may explain our results with desferrioxamine in the animal studies and suggests that effective iron chelation and its removal may modify the inflammatory process in man.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ambruso D. R., Johnston R. B., Jr Lactoferrin enhances hydroxyl radical production by human neutrophils, neutrophil particulate fractions, and an enzymatic generating system. J Clin Invest. 1981 Feb;67(2):352–360. doi: 10.1172/JCI110042. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Babior B. M. Oxygen-dependent microbial killing by phagocytes (first of two parts). N Engl J Med. 1978 Mar 23;298(12):659–668. doi: 10.1056/NEJM197803232981205. [DOI] [PubMed] [Google Scholar]
- Blake D. R., Hall N. D., Treby D. A., Halliwell B., Gutteridge J. M. Protection against superoxide and hydrogen peroxide in synovial fluid from rheumatoid patients. Clin Sci (Lond) 1981 Oct;61(4):483–486. doi: 10.1042/cs0610483. [DOI] [PubMed] [Google Scholar]
- Gutteridge J. M., Paterson S. K., Segal A. W., Halliwell B. Inhibition of lipid peroxidation by the iron-binding protein lactoferrin. Biochem J. 1981 Oct 1;199(1):259–261. doi: 10.1042/bj1990259. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gutteridge J. M., Richmond R., Halliwell B. Inhibition of the iron-catalysed formation of hydroxyl radicals from superoxide and of lipid peroxidation by desferrioxamine. Biochem J. 1979 Nov 15;184(2):469–472. doi: 10.1042/bj1840469. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gutteridge J. M. The measurement of malondialdehyde in peroxidised ox-brain phospholipid liposomes. Anal Biochem. 1977 Sep;82(1):76–82. doi: 10.1016/0003-2697(77)90136-1. [DOI] [PubMed] [Google Scholar]
- Halliwell B. The biological effects of the superoxide radical and its products. Bull Eur Physiopathol Respir. 1981;17 (Suppl):21–29. [PubMed] [Google Scholar]
- Muirden K. D., Senator G. B. Iron in the synovial membrane in rheumatoid arthritis and other joint diseases. Ann Rheum Dis. 1968 Jan;27(1):38–48. doi: 10.1136/ard.27.1.38. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wills E. D. Mechanisms of lipid peroxide formation in animal tissues. Biochem J. 1966 Jun;99(3):667–676. doi: 10.1042/bj0990667. [DOI] [PMC free article] [PubMed] [Google Scholar]