Effect of chronic liver failure on the function and expression of P-GP and MRP2 in rat brain

The purpose of the study was to investigate whether chronic liver failure (CLF) induced by thioacetamide (TAA) affected the function and expression of P-glycoprotein (P-GP) and multidrug resistance-associated protein 2 (MRP2) in rat brain.CLF was induced by ip injection of TAA (200 mg/kg) twice per week for 12 weeks.The rats were used for further experiments 24 h after the last administration.The function of P-GP and MRP2 in rat brain was determined using the brain-to-plasma ratios of corresponding substrates (rhodamine 123,Rho123 and vincristine,VCR for P-GP;Sulfobromophthalein,BSP and dinitrophenyl-S-glutathione,DNP-SG for MRP2);Western blot was applied to determine the expression of P-GP and MRP2 proteins.The results suggested that CLF increased the brain-to-plasma ratios of Rho 123 and VCR,while decreasing those of BSP and DNP-SG.Western blot results showed that CLF decreased brain P-GP levels,while increasing MRP2 levels.In conclusion,CLF may decrease the function and expression of P-GP,while increaseing the function and expression of MRP2.