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Preliminary studies on phospholipase A 2 ‐induced mouse paw edema as a model to evaluate antiinflammatory agents
Author(s) -
Marshall L. A.,
Chang J. Y.,
Calhoun W.,
Yu J.,
Carlson R. P.
Publication year - 1989
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240400203
Subject(s) - cyproheptadine , pharmacology , edema , cyclooxygenase , chemistry , autacoid , in vivo , dexamethasone , phospholipase a , phospholipase a2 , endocrinology , medicine , biochemistry , enzyme , receptor , biology , serotonin , microbiology and biotechnology
Phospholipase A 2 (PLA 2 ) 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 2 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 μg of snake venom PLA 2 ( A. piscivorus piscivorus , 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 2 since edema was negated by enzyme pretreatment with p‐bromophenacyl bromide, a nonspecific PLA 2 inhibitor. Moreover, injection of a protein such as bovine serum albumin did not result in significant edema. Coinjection of phenidone (lipoxygenase inhibitor, 50 μg), indomethacin (cyclooxygenase inhibitor, 50 μg), cyproheptadine (antihistamine/antiserotonin, 50 μg), aristolochic acid (putative PLA 2 inhibitor, 100 μg), or kadsurenone (PAF antagonist, 50μg) with PLA 2 (1 μg/paw) resulted in partial reduction (44.5, 34.2, 54.7, 64, and 50% inhibition, respectively) of edema formation. Oral administration of cyproheptadine (10 mg/kg), indomethacin (10 mg/kg), BW 755c (100 mg/kg), or dexamethasone (1 mg/kg) 1–3 h before challenge also decreased PLA 2 ‐induced edema (63.0, 30.1, 47.8, or 62.5% inhibition, respectively). The data suggest that mouse paw edema resulting from PLA 2 injection is a multicomponent event, influenced by both autacoids and lipid mediators of inflammation.