Role of oxygen radicals and arachidonic acid metabolites in the reverse passive Arthus reaction and carrageenin paw oedema in the rat. |
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Authors: | N. K. Boughton-Smith A. M. Deakin R. L. Follenfant B. J. Whittle L. G. Garland |
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Affiliation: | Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent. |
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Abstract: | 1. The role of arachidonic acid metabolites and oxygen radicals in carrageenin-induced rat paw oedema and dermal reverse passive Arthus reaction (RPA) have been investigated. 2. Indomethacin (10 mg kg-1, p.o.) inhibited carrageenin paw oedema when administered 30 min before, but not 2 h after carrageenin. BWB70C (10 mg kg-1, p.o.), a selective inhibitor of 5-lipoxygenase, had no effect whether administered before or after carrageenin. Administration of both indomethacin and BWB70C had no greater anti-inflammatory effect than indomethacin alone. 3. BW755C (20 mg kg-1, p.o.), which inhibits the cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism, or superoxide dismutase-polyethylene glycol conjugate (SOD-PEG, 3000 u, i.v.) inhibited carrageenin paw oedema whether administered either 30 min before, or 2 h after carrageenin. 4. Pretreatment with dexamethasone (0.1 mg kg-1) or colchicine (2 mg kg-1), likewise suppressed carrageenin paw oedema. 5. BW755C (25-100 mg kg-1, p.o.) dose-dependently reduced plasma leakage in the RPA, whereas indomethacin (5 mg kg-1, p.o.) or BWB70C either alone or in combination, did not. 6. SOD-PEG (300-3000 u, i.v.) dose-dependently inhibited plasma leakage in the RPA. In addition, the iron chelator and peroxyl radical scavenger, desferrioxamine (200 mg kg-1, s.c.) also inhibited plasma leakage. 7. Pretreatment with dexamethasone (0.1 mg kg-1) or colchicine (1 mg kg-1) reduced the plasma leakage in RPA, whereas MK-886 (10 mg kg-1) had no effect.(ABSTRACT TRUNCATED AT 250 WORDS) |
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