QUANTITATIVE STUDIES CONCERNING KAOLIN EDEMA FORMATION IN RATS

¹ The Wellcome Research Laboratories, Burroughs Wellcome & Co. (U.S.A.) Inc., Tuckahoe, New York

Following a subplantar injection of 5.0 mg of kaolin in rats, the time curve of the developing edema volume is biphasic over the first 7 hr. There is a rapid rise initially which diminishes in 1 hr, and a second phase which accelerates sharply from the 4th through the 7th hr. A reduction of the dose of kaolin to 0.20 mg eliminated the second phase but did not change the first phase volume. Additional evidence for the independent character of the two phases was garnered from drug inhibition studies. Hydrocortisone and corticosterone were inactive against the first phase but very potent inhibitors of the second. The corticoid-insensitive phase represented approximately 40% of the 5-hr edema volume and, therefore, an inhibition of 60% was the maximum that could be achieved in this time interval with these hormones. Restricting the edema-inhibition studies with the adrenal corticoids solely to their effect on the second phase resulted in a more sensitive test and a steeper dose-response curve. Acetylsalicylic acid was equipotent against the two phases. Phenylbutazone was more potent against the second phase than against the first. In studies restricted to the second phase, the dose-response curve to phenylbutazone from 10 to 40 mg/kg was steep. At doses larger than 40 mg/kg the response was not dosedependent.

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