Does paracellular permeability play a role in cholephilic dye-induced cholestasis?
Changes in hepatic paracellular permeability were investigated during the development of cholephilic dye-induced cholestasis in rats. For this purpose, four dyes with different cholestatic potency (phenol red, sulfobromophthalein, bromcresol green and rose bengal) were infused at a high, potentially damaging dose (280 nmol/min per 100 g body wt., i.v.), and changes in paracellular permeability were continuously monitored by measuring the access into bile of the permeability probe -14C-sucrose. The cholestatic potency of the different dyes was: rose bengal > bromcresol green > sulfobromophthalein > phenol red. All dyes increased [14C]sucrose bile-to-plasma ratio, producing a displacement towards curves of higher permeability. The capability of the dyes to increase biliary permeability followed the same order as their respective cholestatic potencies. The possible implications of the present results for cholephilic dye-induced cholestasis are discussed.
Roma
M G
MG
Instituto de Fisiología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET -- U.N.R., Rosario, Argentina.
Crocenzi
F A
FA
Rodríguez Garay
E A
EA
D000818:Animals; D001646:Bile / Q000737:chemistry / Q000502:physiology; D001659:Biliary Tract / Q000187:drug effects* / Q000378:metabolism; D001961:Bromcresol Green / Q000008:administration & dosage / Q000032:analysis / Q000633:toxicity; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002779:Cholestasis / Q000139:chemically induced* / Q000378:metabolism; D004396:Coloring Agents / Q000008:administration & dosage / Q000633:toxicity*; D007275:Injections, Intravenous; D007365:Intercellular Junctions / Q000378:metabolism; D008111:Liver Function Tests; D008297:Male; D010637:Phenolsulfonphthalein / Q000008:administration & dosage / Q000032:analysis / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012395:Rose Bengal / Q000008:administration & dosage / Q000032:analysis / Q000633:toxicity; D013395:Sucrose / Q000378:metabolism; D013448:Sulfobromophthalein / Q000008:administration & dosage / Q000032:analysis / Q000633:toxicity; D013997:Time Factors
D004396:Coloring Agents; D013448:Sulfobromophthalein; D012395:Rose Bengal; D013395:Sucrose; D001961:Bromcresol Green; D010637:Phenolsulfonphthalein