3. EFFECT OF ACETAMINOPHEN ON INTESTINAL P-GLYCOPROTEIN ACTIVITY.

NOVAK A.; DELLI CARPINI G.; RUIZ ML.; LUQUITA MG.; RUBIO M.; MOTTINO AD.; GHANEM CI.

Andover NH

Congreso; The Gordon Research Conference on Cellular & Molecular Mechanisms of Toxicity; 2013

The Gordon Conference

Acetaminophen (AP) induces long-term regulation of expression of intestinal Pglycoprotein (P-gp). Whether it can acutely modulate P-gp activity is unknown. Aims: To study the effect of AP on rat intestinal P-gp activity in vivo and in vitro. M&M: In vitro. Intestinal everted sacs were filled with rhodamine 123 (serosal), a tipical P-gp substrate, (R123; 4.5; 9; 12;18 or 36 μM) and incubated in KH buffer (mucosal) alone or with AP (100 μM) and secretion of R123 was assessed along a 40-min period. Serosal-mucosal transport of AP was studied in a similar fashion, in the presence/absence of Psc 833 (10 μM), a specific inhibitor of P-gp. Transport of AP (10 μM) was also evaluated in P-gp knock down HepG2 cells. In vivo. Intestinal absorption of digoxin (Dig, 25.6 nmol/kg) was studied by portal vein sampling (30?min period) in the presence or absence of AP (100 μM). Results: R123 transport adjusted well to a sigmoideal curve. Its Vmax was decreased by AP (P