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Changes of Transporters and Drug-metabolizing Enzymes in Nephrotic Syndrome

Author(s):

Yaqian Dong, Linna Gong, Xianyuan Lu, Mingguang Ye, Yu Lin, Shuting Xie, Jiaxing Zhang, Fenghua Zhou, Lan Tang, Wei Zou and Menghua Liu*   Pages 1 - 11 ( 11 )

Abstract:


Background: Dug-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 of the expression of enzymes and transporters in the disease state are still unclear.

Objective: Our study was to investigate the changes of the expression of main enzymes and drug transporters distributed in Adriamycin nephropathy rat liver, kidney and intestine.

Method: 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 kidney, a greater expression of Mdr1, Mrp2, Mrp4 Oat2 and Oct2 mRNA was found in AN rats as compared with control rats. In liver, the expression of Bcrp mRNA was more doubled or trebled than control groups and a 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 duodenum, the expression of Mdr1 and Mrp3 mRNA level was decreased, while Bcrp and Mrp2 mRNA was increased.

Conclusion: The changes of 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.

Keywords:

Nephrotic syndrome, Adriamycin, drug interaction, drug disposition, transporters, metabolic enzymes

Affiliation:

Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, Guangdong, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, NHC key laboratory of birth defects research, prevention and treatment, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan 410008, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong



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