Central administration of perfluorooctanoic acid inhibits cutaneous inflammation
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Objective: To elucidate the site of action of perfluorooctanoic acid (PFOA) in the carrageenan model of peripheral inflammation.
Subjects: Male Sprague-Dawley rats.
Treatment: We first compared the anti-edema effects of systemic PFOA (50–150 mg/kg) with prototypical nonsteroidal (acetylsalicylic acid, ASA, 50–200 mg/kg) and steroidal (dexamethasone, 0.5–5.0 mg/kg) drugs after the intraplantar injection of carrageenan (1%). We then compared the anti-edema effects of systemic PFOA with local intraplantar (10 mg/kg), and intracerebroventricular (i.c.v., 0.1–50 μg) routes of administration.
Results: Systemic PFOA was at least as or more efficacious than ASA or dexamethasone in reducing carrageenan-induced edema. RU-486 did not change the anti-edema effect of PFOA, ruling out a contribution of endogenous release of glucorticoids. I. c. v. PFOA, but not perfluorooctanes, dramatically reduced multiple signs of inflammation at doses well below the systemically-effective dose. We conclude that the anti-edema effect of high systemic doses of PFOA (≥100 mg/kg, i. p.) is mediated in part by actions in the brain.
Key words.Carrageenan PFOA Aspirin Dexamethasone Nuclear hormone receptor Brain
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