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Anti‐edema Effrect of PPAR Agonists: Similarities and Dissimilarities With Asiprin and Dexamethasone
Author(s) -
Badr Mostafa Z.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.648
Subject(s) - agonist , edema , dexamethasone , medicine , inflammation , pharmacology , peroxisome proliferator activated receptor , endocrinology , aspirin , chemistry , signal transduction , receptor , biochemistry
In this study, we sought to identify molecular targets of PPAR alpha and gamma agonists as antiiflammatory agents by comparing characteristics of their anti‐edema effect with those exerted by dexamethasone (DEX) and aspirin (ASA). Carrageenan was injected in the midplantar region of the right hindpaw of male Sprague‐Dawley rats, and edema, reflected as an increase in dorsal‐to‐ventral paw thickness, was measured with a microcaliper. When administered intraperitoneally 30 minutes prior to carrageenan, the PPARα agonist PFOA, the PPARγ agonist L805645, DEX, and ASA caused significant dose‐dependent decreases in paw edema, with DEX being less efficacious than both PFOA and ASA. Furthermore, PFOA and ASA, but not DEX, diminished paw edema when given after carrageenan. Subsequently, in order to elucidate whether the anti‐edema effect of PPAR agonists, ASA or DEX results from the activation of a common signal transduction pathway, we evaluated the impact of simultaneous treatment with PFOA and maximally‐effective doses of L805645, DEX or ASA. Only the combination of PFOA and DEX produced an additive anti‐edema effect. Based on our findings we conclude that PPARα and PPARγ agonists regulate inflammation through a common mechanism that is different from that ascribed to steroids. Whether PPAR agonists and aspirin, which do not activate PPARs, share a common signal transduction pathway remains to be investigated.