Characterization of the mechanisms involved in the increased renal elimination of bromosulfophthalein during cholestasis: involvement of Oatp1.

Abstract

The kidneys and liver are the major routes for organic anion elimination. We have recently shown that acute obstructive jaundice is associated with increased systemic and renal elimination of two organic anions, p-aminohippurate and furosemide, principally excreted through 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 techniques. Renal organic anion-transporting polypeptide 1 (Oatp1) expression was evaluated by immunoblotting and IHC. Excreted, filtered, and secreted loads of BSP were all higher in BDL rats compared with Sham rats. The higher BSP filtered load resulted from the increase in plasma BSP concentration in BDL rats, because glomerular filtration rate showed no difference with the 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 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.

• Authors: Anabel Brandoni, Adriana Mónica Torres
• Journal: The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society (J Histochem Cytochem) Vol. 57 Issue 5 Pg. 449-56 (May 2009) ISSN: 0022-1554 [Print] United States
• PMID: 19153193 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anions
• Organic Anion Transporters, Sodium-Independent
• Slco1a1 protein, rat
• Sulfobromophthalein

Topics

• Acute Disease
• Animals
• Anions
• Cholestasis, Extrahepatic (metabolism)
• Immunoblotting
• Immunohistochemistry
• Jaundice, Obstructive (metabolism)
• Kidney (metabolism)
• Male
• Microvilli (metabolism)
• Organic Anion Transporters, Sodium-Independent (biosynthesis, physiology)
• Rats
• Rats, Wistar
• Sulfobromophthalein (pharmacokinetics)