Enhancement of carrageenan and dextran-induced edemas by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds.
Paw edema formation after the subplantar injection of carrageenan was enhanced in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The enhanced carrageenan response could be detected as early as 4.5 hr after TCDD; however, the magnitude of enhancement was greatest when rats were challenged with carrageenan 5 days after TCDD. In the latter case, the ED50 of TCDD in enhancing the carrageenan response was 6 micrograms/kg. TCDD also enhanced dextran-induced paw edema, which follows a time course different from that of carrageenan-induced edema and is produced by a different mechanism. The enhancement of carrageenan and dextran paw edemas was due to an increase in the edema-producing potency of the irritants and not to a change in their maximum effect. The ability of other 3-methylcholanthene-type inducers to enhance carrageenan-induced paw edema and the inability of phenobarbital-type inducers to cause the response suggest that the TCDD binding protein might be involved in edema enhancement. TCDD also enhanced carrageenan-induced pleural edema; however, the number and type of leukocytes recovered in the pleural exudate was not affected. TCDD did not alter granuloma formation produced by the subcutaneous implantation of cotton pellets, indicating that enhancement by TCDD was peculiar to edema formation and not to inflammation in general. It is suggested that TCDD may enhance carrageenan and dextran edemas by increasing the availability of mediators involved in each type of edema formation and/or by increasing the responsiveness of the vasculature to mediators.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002351:Carrageenan / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003911:Dextrans / Q000633:toxicity*; D004147:Dioxins / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004487:Edema / Q000503:physiopathology*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013950:Thymus Gland / Q000187:drug effects
D003911:Dextrans; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D008748:Methylcholanthrene; D002351:Carrageenan; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital