Effect of cholephilic dyes on hepatic tight junctional permeability in the rat.
Changes in biliary permeability during cholephilic dye-induced choleresis, as assessed by measuring the movement into bile of two permeability probes, [14C]sucrose and horseradish peroxidase, were analyzed following an i.v. infusion (60 nmol/min per 100 g body wt) of the model cholephilic organic anion sulfobromophthalein in rats. Dye infusion led to a progressive increase of the [14C]sucrose bile-to-plasma ratio, which reached a maximum value after 100 min of dye infusion (+97%). Paracellular entry of horseradish peroxidase, as evaluated by the early peak of its biliary appearance curve, was also selectively increased (+69%), without changes in the later (transcytotic) access of the protein. Additional dose-response studies of biliary permeability to [14C]sucrose, using sulfobromophthalein and rose bengal, showed that this effect was dose-dependent and rapidly reversed by interruption of dye administration. The influence of hydrophobic/hydrophilic balance on this effect was also studied by infusing four dyes covering a broad range of hydrophobicity (phenol red, bromocresol green, sulfobromophthalein, and rose bengal), so as to attain a similar value of dye hepatic content at the end of the experiment (approximately 150 nmol/g liver wt). Under these conditions, a strong positive correlation was found between the increase in biliary permeability to [14C]sucrose and dye hydrophobicity. These results suggest that cholephilic dyes increase tight junctional permeability in a reversible and dose-dependent manner, and that this effect depends on the hydrophobic/hydrophilic balance of the dye.
Roma
M G
MG
Instituto de Fisiología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET-U.N.R., Rosario, Argentina.
Marinelli
R A
RA
Crocenzi
F A
FA
Rodríguez Garay
E A
EA
D000818:Animals; D001646:Bile / Q000378:metabolism; D004396:Coloring Agents / Q000494:pharmacology*; D003135:Common Bile Duct / Q000187:drug effects* / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000378:metabolism; D007262:Infusions, Intravenous; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013395:Sucrose / Q000378:metabolism; D013448:Sulfobromophthalein / Q000494:pharmacology*; D019108:Tight Junctions / Q000187:drug effects*
D004396:Coloring Agents; D013448:Sulfobromophthalein; D013395:Sucrose; D006735:Horseradish Peroxidase