Improvement in renal excretion of different organic anions in rats with extrahepatic cholestasis

BRANDONI ANABEL; VILLAR, SILVINA RAQUEL; QUAGLIA, NORA; TORRES, ADRIANA MONICA

Salvador de Bahia, Brazil

Congreso; The Biennal Scientific Meeting of the International Association for the Study of the Liver (IASL), Salvador de Bahía, Brazil;; 2004

International Association for the Study of the Liver (IASL).

Modifications in hepatic excretion of organic anions have been demonstrated in rats with extrahepatic cholestasis (EHC). The purpose of the present study was to evaluate, in rats with acute bile duct ligation, the urinary excretion of two different organic anions, p-aminohippurate (PAH) mainly excreted by the kidneys and sulfobromophthalein (BSP) mainly excreted by the liver. EHC was produced in adult male Wistar rats by ligation of the common bile duct during 21 hours (BDL). A group of Sham rats (S) was also processed. The cholestasis was evidenced by determining total and direct bilirubin plasma levels (TB, DB, mg/L). One pharmacokinetic study was done by the administration of a single dose of PAH (30 mg/kg b.w., i.v.) (S, n=6; BDL, n=4). The other one was performed by administration of a single bolus of BSP (10 mg/kg b.w., i.v.) (S, n=7; BDL, n=8). The following parameters were determined: systemic clearance of PAH and BSP (ClPAH, ClBSP; mL/min/100g b.w.), total amount of PAH and BSP excreted in urine (PAHu, mg; BSPu, m g) during the corresponding experiment. At the end of these studies, the kidneys were rapidly removed in order to obtain basolateral plasma membranes (BLM). The abundance of Organic Anion Transporter 1 (OAT1, %) and BSP/Bilirubin Binding Protein (BBBP, %) were studied by immunoblot technique in BLM. Results (*P<0.05): TB: S=5.3±0.4, BDL= 43.7±3.0*; DB: S=2.3±0.2, BDL=34.4±3.7*; ClPAH: S=2.82±0.22, BDL=3.55±0.06*; ClBSP: S=0.81±0.08, BDL=0.19±0.03*; PAHu: S=2.9±0.1, BDL=3.7±0.3*; BSPu: S=1.92±0.34, BDL=32.40±11.93*; OAT1: S=100±7, BDL=139±11*; BBBP: S=100±10, BDL=173±3*. Conclusion: The higher abundances of the two organic anions carriers detected in rats with EHC might explain the higher renal capacity to eliminate distinct negatively charge compounds in this group of rats. These results suggest a relevant role of these transporters in renal elimination of those organic anions excreted mainly by liver, in the presence of the obstructive cholestasis.