Expression and function of P-glycoprotein in rats with glycerol-induced acute renal failure

The effect of glycerol-induced acute renal failure on P-glycoprotein expression and function was evaluated in rats. The in vivo function of P-glycoprotein was evaluated by measuring renal secretory and biliary clearance and brain distribution of rhodamine 123 (Rho-123), a P-glycoprotein substrate, under a steady-state plasma concentration. In acute renal failure rats, the P-glycoprotein level increased 2.5-fold in the kidney, but not in the liver and brain. In contrast, P-glycoprotein function in these tissues was suppressed. Interestingly, not only the renal but also the biliary clearance of Rho-123 was correlated with the glomerular filtration rate. In Caco-2 cells, plasma from renal failure rats exhibited a greater inhibitory effect on P-glycoprotein-mediated transport of Rho-123 than did plasma from control rats. In conclusion, P-glycoprotein function was systemically suppressed in acute renal failure, even though the level of P-glycoprotein remained unchanged or rather increased. This may be due to the accumulation of some endogenous P-glycoprotein substrates/modulators in the plasma in disease states.