ROLE OF OXYGEN RADICALS AND ARACHIDONIC-ACID METABOLITES IN THE REVERSE PASSIVE ARTHUS REACTION AND CARRAGEENAN PAW EDEMA IN THE RAT

1 The role of arachidonic acid metabolites and oxygen radicals in carr ageenin-induced rat paw oedema and dermal reverse passive Arthus react ion (RPA) have been investigated. 2 Indomethacin (10 mg kg-1, p.o.) in hibited carrageenin paw oedema when administered 30 min before, but no t 2 h after carrageenin. BWB70C (10 mg kg-1, p.o.), a selective inhibi tor of 5-lipoxygenase, had no effect whether administered before or af ter carrageenin. Administration of both indomethacin and BWB70C had no greater anti-inflammatory effect than indomethacin alone. 3 BW755C (2 0 mg kg-1, p.o.), which inhibits the cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism, or superoxide dismutase-polye thylene glycol conjugate (SOD-PEG, 3000 u, i.v.) inhibited carrageenin paw oedema whether administered either 30 min before, or 2 h after ca rrageenin. 4 Pretreatment with dexamethasone (0.1 mg kg-1) or colchici ne (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 R PA, whereas indomethacin (5 mg kg-1, p.o.) or BWB70C either alone or i n 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 in hibited 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. 8 These results indicate an import ant role for oxygen radicals but not arachidonic acid metabolites in t he maintenance of carrageenin paw oedema and the plasma leakage in RPA . Furthermore, the results suggest that the anti-inflammatory actions of BW755C can be dissociated from its effects on arachidonic acid meta bolism and are attributed to its anti-oxidant activity.