Role of oxygen radicals and arachidonic acid metabolites in the reverse passive Arthus reaction and carrageenin paw oedema in the rat

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-', p.o.) inhibited carrageenin paw oedema when administered 30 min before, but not 2 h after carrageenin. BWB70C (10 mg kg-', 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-, 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-') or colchicine (2 mg kg-'), likewise suppressed carrageenin paw oedema. 5 BW755C (25-100mgkg-', p.o.) dose-dependently reduced plasma leakage in the RPA, whereas indomethacin (5mgkg-', 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 (200mgkg-', s.c.) also inhibited plasma leakage. 7 Pretreatment with dexamethasone (0.1 mg kg-') or colchicine (1 mg kg-l) reduced the plasma leakage in RPA, whereas MK-886 (10mgkg-1) had no effect. 8 These results indicate an important role for oxygen radicals but not arachidonic acid metabolites in the 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 metabolism and are attributed to its anti-oxidant activity.

Inducible isoforms of cyclooxygenase and nitric-oxide synthase in inflammation.

“…The relative contributions of COX-1 and COX-2 to this PG release are not yet determined. Interestingly, indomethacin inhibits carrageenin edema in the rat paw when given before the carrageenin but not when given 2 hr afterward (49).…”

Platelet‐activating factor: the effector of protein‐rich plasma extravasation and nitric oxide synthase induction in rat immune complex peritonitis

“…[895][896][897][898][899][900][901] in the triggering of other mediators. Recent studies have emphasized the involement of nitric oxide in the production of tissue injury in a model of alveolitis and dermal vasculitis analogous to RPA (Mulligan et al, 1991;1992), whereas there has been some controversy regarding the possible involvement of eicosanoids in the mediation of plasma leakage in RPA (Boughton-Smith et al, 1993). The purpose of this study was to assess the effect of blocking receptors for the lipid mediator platelet-activating factor on events of the RPA that occur at different times after antigen challenge.…”

Evaluation of Anti-Inflammatory Activity of Pseudananas macrodontes (Morr.) Harms (Bromeliaceae) Fruit Extract in Rats

“…The initial phase of edema formation (0 -1 h), which is not inhibited by NSAIDs, is attributed to the release of histamine and serotonin (Di Rosa et al, 1971). The second phase (1 -6 h) is associated with a local infi ltration and activation of neutrophils (Boughton-Smith et al, 1993) and the production of prostaglandins (Di Rosa et al, 1971), which has been attributed to the induction of COX-2 ( Nantel et al, 1999). An increase in NO production is also associated with the increase of paw volume (Salvemini et al, 1996).…”