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 non-steroidal (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.
Bibliographical noteFunding Information:
Acknowledgements. Supported by NS45954 and DA10356 to BKT.
- Nuclear hormone receptor