Effect of lipopolysaccharide on P-glycoprotein-mediated intestinal and biliary excretion of rhodamine123 in rats

Abstract

The effects of lipopolysaccharide (LPS) on the ileal and biliary excretion of rhodamine123 were investigated in rats at different times after intraperitoneal (i.p.) injection (1 mg/kg and 5 mg/kg of body weight). P-gp protein decreased 8 h after injection of LPS and returned to the control level 24 h after i.p. injection of LPS in the ileum. There was a marked decrease in the expression level of mdr1a mRNA in the ileum and liver 8 h after i.p. injection of LPS when compared with the control condition. Also, the ileal and biliary clearance of rhodamine123 significantly decreased 8 h after i.p. injection of LPS, but returned to the control levels 24 h after i.p. injection of LPS. These results suggest that LPS-induced decreases in P-gp-mediated ileal and biliary excretion of rhodamine123 were probably due to impaired P-gp-mediated transport ability. The levels of iNOS and IL-1β mRNA in the ileum and liver increased 2 and 8 h after i.p. injection of LPS, respectively, and returned to the control levels 24 h after injection of LPS. These findings suggest that LPS markedly decreases P-gp-mediated ileal and biliary excretion of rhodamine123, probably by partly decreasing the expression of P-gp protein levels, likely due to increased lipid peroxidation levels through iNOS mRNA and inflammatory mediators such as IL-1β.