Effects of Intestinal Ischemia/Reperfusion on P-Glycoprotein Mediated Biliary and Renal Excretion of Rhodamine123 in Rat

Summary:To analyze the effects of I/R on P-gp function in liver and kidney, biliary and urinary excretions of rhodamine123 as a substrate of P-gp were examined in rats. The effects of reperfusion time on change and recovery of P-gp function were also examined. The biliary and renal clearance of rhodamine123 significantly decreased at 3 hr after reperfusion, but returned to control levels at 24 hr after reperfusion. These results suggest that intestinal I/R-induced decrease in P-gp-mediated biliary and renal excretion of rhodamine123 is litely due to impairment of P-gp-mediated transport ability. The level of P-gp protein in liver decreased and that of iNOS mRNA increased at 3 hr after reperfusion and both levels returned to control levels at 24 hr after reperfusion. No marked change in the levels of P-gp protein and iNOS mRNA was observed in kidney at 3 hr and 24 hr after reperfusion. Thus, decrease in biliary excretion of rhodamine123 would appear due in part to decrease in expression of P-gp, caused by increase in lipid peroxidation levels through iNOS mRNA.