Background: Drug-metabolizing enzymes and transporters play key roles in drug disposition and drug
interactions. The alterations of their expression will influence drug pharmacokinetics and pharmacodynamics.
However, the changes in the expression of enzymes and transporters in the disease state are still unclear.
Objective: Our study was to investigate the changes in the expression of main enzymes and drug transporters
distributed in Adriamycin nephropathy rat liver, kidney, and intestine.
Methods: An intravenous injection with a single dose of Adriamycin (6mg/kg) was made to establish Adriamycin
nephropathy (AN) model and normal groups were injected with normal saline. Serum was collected for lipid
metabolism, renal, and hepatic function measurement. The real-time PCR and western blot were applied to determine
the mRNA and protein expression of drug enzymes and transporters.
Results: In the kidney, a greater expression of Mdr1, Mrp2, Mrp4 Oat2 and Oct2 mRNA was found in AN rats as
compared with control rats. In the liver, the expression of Bcrp mRNA was more doubled or tripled than control
groups and downregulation of Mdr1, Mrp2, Mrp4 and Bsep gene expression was found in AN rats. Besides, we
observed a downward trend of Cyp1a2, Cyp3a4 and Cyp2c9 mRNA levels in AN groups. In the duodenum, the
expression of Mdr1 and Mrp3 mRNA level was decreased, while Bcrp and Mrp2 mRNA were increased.
Conclusion: The changes in drug-metabolizing enzymes and transporters expression in AN rats were clarified, which
may be beneficial for understanding the altered pharmacokinetics and pharmacodynamics of clinical drugs and
reduce unexpected clinical findings for nephropathy patients.