Endotoxin Downregulate Hepatic Expression of P-Glycoprotein and MRP2 in 2-Acetylaminofluorene-Treated Rats

摘要

In liver, the ATP-dependent transporters P-glyco protein (PGP) and multidrug resistance protein-~ (MRP2) are involved in the secretion of numerou! drugs and toxins in bile. Although constitutive levell of PGP and MRP-2 are decreased in rat liver aftel exposure to endotoxin, it is possible that inducec forms of these transporters may be alternately af fected. In vitro, the hepatocarcinogen, 2-acetylamino fluorene (AAF) induces expression of PGP and MRP2 Thus, we examined the influence of endotoxin on thE expression ofPGP and MRP2 in AAF-treated rats. Ex pression of PGP and MRP2 was analyzed on Westernl and by RT-PCR in livers obtained from endotoxin an() control groups. In vivo, AAF treatment significantl~ induced PGP/mdrl expression and imposed a signifi, cant reduction in the expression of spgp. MRP2 pro, tein and mRNA levels were not altered by AAF admin istration. Endotoxin administration to both AAF, treated and non-AAF-treated rats elicited significanj reductions in the protein and mRNA expression oj MRP2 and PGP (P < 0.05). Our data indicate that en. dotoxin suppresses the overexpression of PGP an