Central administration of perfluorooctanoic acid inhibits cutaneous inflammation.
OBJECTIVE
To elucidate the site of action of perfluorooctanoic acid (PFOA) in the carrageenan model of peripheral inflammation.


METHODS
Male Sprague-Dawley rats.


METHODS
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 mug) 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 (> or =100 mg/kg, i. p.) is mediated in part by actions in the brain.
Department of Pharmacology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
B K
BK
Taylor
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Kriedt
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Nagalingam
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Dadia
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Badr
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D002210:Caprylates / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced; D005466:Fluorocarbons / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects* / Q000473:pathology*; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D002210:Caprylates; D005466:Fluorocarbons; D003907:Dexamethasone; C023036:perfluorooctanoic acid