Alteration of P-gp expression after intestinal ischemia-reperfusion following 16-h fasting in rats

Abstract

Alteration of P-glycoprotein (P-gp) expression influences the pharmacokinetics of P-gp substrates after intestinal ischemia-reperfusion (I/R). Fasting before intestinal I/R affects intestinal I/R injury. However, the effect of fasting on the alteration of P-gp expression after intestinal I/R has not been clarified. We previously reported that P-gp expression was altered after intestinal I/R following feeding. In the present study, we investigated the expression of P-gp after intestinal I/R following 16-h fasting. The mdr1a levels were decreased at 6 h in the jejunum, at 1 h in the ileum, at 6 and 24 h in the liver and at 6 h in the kidney. The mdr1b levels were decreased at 6 h in the ileum and at 1 and 6 h in the kidney. The mdr1b level in the liver was increased at 1 and 6 h. The expression of P-gp was decreased at 6 h in the jejunum, at 1, 6 and 24 h in the ileum, and at 6 h in the kidney. These alterations were different to those after intestinal I/R following feeding. In particular, the decrease in P-gp expression in the 16-h fasting I/R rats occurred at an early time during reperfusion compared with that in the feeding I/R rats. In conclusion, feeding condition affects the alteration of P-gp expression after intestinal I/R. Therefore, it is important to understand the patient's feeding condition for safe drug therapy. © 2011 The Pharmaceutical Society of Japan.