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JHC exPRESS: First Published January 19, 2009. doi:10.1369/jhc.2009.952986
Journal of Histochemistry and Cytochemistry
Copyright © 2009 Brandoni & Torres

A more recent version of this article appeared on May 1, 2009.
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Characterization of the Mechanisms Involved in the Increased Renal Elimination of Bromosulfophthalein During Cholestasis: Involvement of Oatp1

Anabel Brandoni 1 and Adriana Mónica Torres 1*

1 Farmacología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas, Rosario, Argentina

* To whom correspondence should be addressed. E-mail: admotorres{at}yahoo.com.ar.

Submitted on October 3, 2008
Accepted on 5 January 2009


  Abstract
The kidneys and liver are the major routes for organic anion elimination. We have recently demonstrated that acute obstructive jaundice is associated with increased systemic and renal elimination of two organic anions, p-aminohippurate and furosemide, principally excreted via urine. This study examined probable adaptive mechanisms involved in renal elimination of bromosulfophthalein (BSP), a prototypical organic anion principally excreted in bile, in rats with acute obstructive jaundice. Male Wistar rats underwent bile duct ligation (BDL rats). Pair-fed sham-operated rats served as controls. BSP renal clearance was performed by conventional technique. Renal organic anion-transporting polypeptide 1 (Oatp1) expression was evaluated by immunoblotting and immunohistochemistry. Excreted, filtered and secreted loads of BSP were all higher in BDL rats compared with Sham ones. The higher BSP filtered load resulted from the increase in plasma BSP concentration in BDL rats, as glomerular filtration rate showed no difference with Sham group. The increase in the secreted load might be explained by the higher expression of Oatp1 observed in apical membranes from kidneys of BDL animals. This likely adaptation to the hepatic injury, specifically in biliary components elimination, might explain, at least in part, the huge increase in BSP renal excretion observed in this experimental model.

Key Words: bromosulfophthalein, organic anions, kidneys, acute jaundice, bile duct obstruction, Oatp1, transporters


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