Eliminación de aniones orgánicos con diferentes vías de excreción preferencial en ratas con colestasis extrahepática de 21 h de duración

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

Rosario

Congreso; XXIII Reunión Anual de la Sociedad de Biología de Rosario.; 2003

Sociedad de Biología. (SBR).

We have described alterations in the pharmacokinetic of organic anions in rats with EHC. The aim of this study was to compare the systemic and renal handling of two organic anions, PAH and BSP in rats with EHC. EHC was produced by bile duct ligation during 21 h (L) in adult male Wistar rats. A group of Sham rats was also processed (S). One group of S (n=6) and L (n=4) received a single dose of PAH (30 mg/kg b.w.). Other group of S (n=7) and L (n=8) received a single dose of BSP (10 mg/kg b.w.). From these studies, systemic clearance of PAH and BSP (ClsPAH; ClsBSP, mL/min/100g) were obtained. The quantity of each drug excreted in urine was also determined (PAHo, mg; BSPo, m g). Basolateral membranes were isolated from renal cortex in order to investigate the abundances of the Organic Anion Transporter 1 (OAT1, %) and BSP/Bilirubin Binding Protein (BBBP, %). In other group of rats (S, n=4; L, n=4), renal plasma flow (RPF, mL/min/100g) was measured by fluorescent microspheres. ClsPAH: S=2.82±0.22, L= 3.55±0.06*; ClsBSP: S=0.81±0.08, L=0.19±0.03*; PAHo: S=2.92 ±0.11, L=3.67±0.31*; BSPo: S=1.92±0.34, L=32.40±11.93*; OAT1: S=100±7, L=139±11*; BBBP: S=100±10, L=173±3*; RPF: S=3.81±0.32, L=2.02±0.30* (*p<0.05). An increase in ClsPAH, anion excreted mainly by kidneys and a decrease in ClsBSP, anion excreted preferentially by liver were observed in rats with EHC. An increment in the quantity of PAH and BSP in urine was found although the lower RPF. This could be explained, at least in part, by the higher abundances of the renal carriers studied in the group of rats with EHC.