Increased permeability of the rat biliary tree by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment and protection by hepatoactive agents.
Male Sprague-Dawley rats were treated ip on Day 0 with 0, 20, 50, or 100 micrograms/kg of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and biliary tree permeability was evaluated on Days 2, 4, 7, 10, 14, or 20 by segmented retrograde intrabiliary injection of [3H]sucrose or [14C]mannitol. Seven days after 100 micrograms/kg TCDD, the percentage recovery in bile of both [3H]sucrose (73.9 +/- 4.2 vs 27.6 +/- 7.6, control vs TCDD, means +/- SE) and [14C]mannitol (22.7 +/- 2.2 vs 12.1 +/- 2.2) was decreased, demonstrating that the permeabilities of both the intracellular (canalicular) and paracellular pathways were increased. Seven days after 50 micrograms/kg TCDD, the recovery of [3H]sucrose was decreased (73.5 +/- 5.4 vs 39.0 +/- 2.8) but the recovery of [14C]mannitol was not (25.5 +/- 1.5 vs 22.9 +/- 1.9). Thus, an increase in paracellular permeability is obtained at a lower dose of TCDD. In rats treated with 100 micrograms/kg TCDD on Day 0, co-treatment with chlordecone (15 mg/kg/day on Days 2-6) or thyroxine (50 micrograms/kg on Day 2) had no effect. Pregnenolone-16 alpha-carbonitrile (75 mg/kg/day on Days 4-6) treatment increased [14C]mannitol recovery in both TCDD and control groups; its effect must not be specific. Methimazole given in drinking water (0.5%) on Days -7 through 7 reversed the increased permeability effects of TCDD (100 micrograms/kg) without affecting the biliary tree permeability ([14C]mannitol recovery) of control animals.
D000818:Animals; D001659:Biliary Tract / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D007631:Chlordecone / Q000494:pharmacology; D004147:Dioxins / Q000494:pharmacology*; D005508:Food Deprivation / Q000502:physiology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008353:Mannitol / Q000378:metabolism; D008713:Methimazole / Q000494:pharmacology; D010539:Permeability; D000072317:Polychlorinated Dibenzodioxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011285:Pregnenolone Carbonitrile / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013395:Sucrose / Q000378:metabolism; D013974:Thyroxine / Q000494:pharmacology
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D011285:Pregnenolone Carbonitrile; D008353:Mannitol; D008713:Methimazole; D013395:Sucrose; D013974:Thyroxine; D007631:Chlordecone