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 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.
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 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.
Authors: Edward Anthony Emmett; Hong Zhang; Frances Susan Shofer; David Freeman; Nancy Virginia Rodway; Chintan Desai; Leslie Michael Shaw Journal: J Occup Environ Med Date: 2006-08 Impact factor: 2.162
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