ININFA   02677
INSTITUTO DE INVESTIGACIONES FARMACOLOGICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Effect of acetaminophen intoxication on intestinal P-glycoprotein expression and activity in rats.
Autor/es:
GHANEM, C. I.; DELLI CARPINI G.; VILLANUEVA,S.S. .; ARIAS A.; MOTTINO,A.D.; RUBIO,M.
Lugar:
Bueno Aires
Reunión:
Congreso; Reunión Anual de la Sociedad Argentina de Farmacología Experimental; 2007
Institución organizadora:
Sociedad Argentina de Farmacología Experimental
Resumen:
Acetaminophen (AP) is the most used analgesic and antipyretic drug. Whether AP affects intestinal barrier, as represented by P-glycoprotein (Pgp), is unknown. The aim of this study was to evaluate the effect of AP intoxication on intestinal Pgp expression and activity in rats. Material and Methods: Male Wistar rats were injected i.p. with 1 g/kg bw of AP (AP Group) or vehicle (C group). Experiments were performed 24 hr after the injection. Pgp expression was evaluated by western blot and its activity using the everted intestinal sac model. The last 10 cm of intestine (next to the ileocecal valve) were filled with rhodamine 123 (15 uM, serosal side) and incubated in Krebs-Henseleit buffer with or without verapamil (100 uM, a Pgp inhibitor, mucosal side). Mucosal samples were taken for 45 min in 5 min-periods. Data are expressed as means ± SD. Results: Intestinal Pgp expression was higher in AP (1244±286) vs C (661±226) (Optical density units, n=3, p<0.05). Pgp activity was increased in AP vs C, the slope (nmol rho/g/min, n=4) of the secretion kinetic curve being 67% higher in AP (0.082±0.016) than in C (0.049±0.003) (p<0.05). The presence of Verapamil inhibited rho transport in AP and  C (slope AP+V: 0.006±0.002 and C+V: 0.007±0.004). Conclusion: induction of P-gp by AP leads to increased membrane barrier activity at the intestine.