Compensation Increase in Organic Anion Excretion in Rats with Acute Biliary Obstruction: Role of the Renal Organic Anion Transporter 1

Abstract

The purpose of the present study was to examine in rats the effects of acute bile duct ligation on the expression of the organic anion transporter 1 in the kidney and the consequences of these effects on the systemic clearance of organic anions, particularly on p-aminohippurate (PAH) clearance, since it has been viewed as the prototypic organic anion. Male Wistar rats underwent bile duct ligation (BDL rats). Pair-fed sham-operated rats served as controls. All studies were carried out 21 h after surgery. Our data revealed that BDL rats had a higher expression of organic transporter 1 protein in kidney cortex homogenates. Accordingly, systemic clearance of PAH and urinary excretion of PAH were both higher in BDL rats. These findings suggest that impairment of the liver function after BDL is followed by a distinct and statistically significant increase in renal excretion of PAH, indicating a possible compensation mechanism.

Expression and Function of Renal Organic Anion Transporters in Cholestasis

“…The higher expression of Oat1 and BBBP at the basolateral domain of renal tubular cells together with the increased expression of Mrp2 at apical membrane could justify the increased excretion of PAH and FS described after 21 h of obstructive jaundice (Brandoni et al, 2003a;Brandoni et al, 2006;Brandoni et al, 2003b;Brandoni et al, 2004a;Brandoni et al, 2004b;Tanaka et al, 2002;Villanueva et al, 2006).…”

“…Burckhardt, 2011). The protein expression of Oat1 was significantly increased both in cortical homogenates and in basolateral membranes from kidneys after 21 hours of BDL (Brandoni et al, 2006a;Brandoni et al, 2003a). This Oat1 up regulation might lead to a higher elimination of its transported compounds.…”

“…Additionally, it was shown increased renal tubular conversion of 1-chloro-2,4-dinitrobenzene (CDNB) to its glutathione conjugate dinitrophenyl-S-glutathione (DNP-SG) followed by subsequent Mrp2-mediated secretion into urine that partially compensates for altered liver function in experimental obstructive cholestasis (Villanueva et al, 2006). It is worth noting that these results might also explain the increase in BSP and PAH excreted load seen in BDL rats (Brandoni & Torres, 2009;Brandoni et al, 2003a).…”

“…Performing bile duct ligation (BDL) as a well-established model of cholestasis (Brandoni & Torres, 2009a), we have determined an increase in the systemic clearance of PAH associated to an increase in the abundance of Oat1 in renal cortex homogenates in rats at 21 h after bile duct ligation (early phase of acute extrahepatic cholestasis) (Brandoni et al, 2003a).…”

“…Recent experiments with tissue from Oat3 knockout mice show reduced uptake of PAH, ES, and taurocholate in renal cortical slices and nearly complete inhibition of transport of the fluorescent organic anion fluorescein in intact choroid plexus (Sweet et al, 2002). Brandoni et al (2003aBrandoni et al ( , 2006a have studied the cortical renal expression of Oat3 in association with the pharmacokinetics and renal excreti o n o f P A H a n d F S i n r a t s w i t h a c u t e extrahepatic cholestasis. Male Wistar rats underwent bile duct ligation (BDL rats).…”