Preliminary studies on phospholipase A2-induced mouse paw edema as a model to evaluate antiinflammatory agents
✍ Scribed by L. A. Marshall; J. Y. Chang; W. Calhoun; J. Yu; R. P. Carlson
- Publisher
- John Wiley and Sons
- Year
- 1989
- Tongue
- English
- Weight
- 468 KB
- Volume
- 40
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Phospholipase A, (PLA2) is a key component of the inflammatory process because of its role in the generation of eicosanoids and platelet-activating factor (PAF). Manipulation of PLA, activity offers a novel therapeutic approach for the development of antiinflammatory agents; however, there is a need for a suitable in vivo model. Injection of 1 fig of snake venom PLA, (A. piscivoruspiscivorus. D-49) into the mouse hind footpad produced a significant three-to four-fold rise in paw edema within 10 min, compared to the saline control. Edema formation depended on enzyme concentration and appeared specific for PLA, since edema was negated by enzyme pretreatment with p-bromophenacyl bromide, a nonspecific PLA, inhibitor. Moreover, injection of a protein such as bovine serum albumin did not result in significant edema. Coinjection of phenidone (lipoxygenase inhibitor, 50 pg), indomethacin (cyclooxygenase inhibitor, 50 pg), cyproheptadine (antihistamine/antiserotonin, 50 pg), aristolcchic acid (putative PLA, inhibitor, 100 pg), or kadsurenone (PAF antagonist, 50pg) with PLA, (1 pg/paw) resulted in partial reduction (44.5, 34.2, 54.7, 64, and 50% inhibition, respectively) of edema formation. Oral administration of cyproheptadine (1 0 mg/kg), indomethacin (10 mg/kg), BW 755c (100 mg/kg), or dexamethasone (1 mg/kg) 1-3 h before challenge also decreased PLA,-induced edema (63.0, 30.1,47.8, or 62.5% inhibition, respectively). The data suggest that mouse paw edema resulting from PLA, injection is a multicomponent event, influenced by both autacoids and lipid mediators of inflammation.