Induction of intestinal P-glycoprotein (Pgp) expression and activity by sub-toxic doses of acetaminophen (AP) in rat intestine and human LS174T cells

GHANEM, C. I.; ARIAS A.; VILLANUEVA,S.S.; NOVAK, A.; FILLIA, M. F.; DELLI CARPINI G.; MARÍN, J. J. G.; MOTTINO,A.D; RUBIO M. C.

Anaheim, L A, EEUU

Congreso; Experimental Biology 2010; 2010

American Society of Pharmacological and Experimental Therapeutics

AP induced liver Pgp expression and activity in rats. Aim: to study the effect of sub-toxic doses of AP on intestinal Pgp expression in rats and in a human intestinal cell line. M&M: Male Wistar rats were injected i.p. for 3 days with 0.2; 0.3; and 0.6 g/kg b.w. of AP (AP group) or vehicle (C group) (n=4). One day later Pgp expression and activity were evaluated by western-blotting and rhodamine 123 (R123, 15 uM) serosal to mucosal transport in ileum isolated sacs with or without verapamil (V, 100 uM). Intestinal human LS174T cells were exposed to a sub-toxic dose of AP (5 mM) for 48 hs, then Pgp expression was evaluated by QPCR and R123 efflux was determined by  flow citometry with or without V. Results: Ileum Pgp expression increased in AP vs C (160%, P<0.05). Cumulative R123 secretion was 44% higher in AP group (P<0.05). V inhibited R123 transport in both AP and C. Cells exposed to AP expressed 60% more protein and presented 80% more activity than control cells (P<0.05). Conclusion: Sub-toxic doses of AP induced intestinal Pgp expression and activity in rats and in a human intestinal cell line. This suggests potential drug-drug interactions when AP is co-administered with other Pgp substrates