Dioscin protects against ANIT–induced cholestasis via regulating Oatps, Mrp2 and Bsep expression in rats

Journal Article · Mon Aug 15 04:00:00 EDT 2016 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2016.06.019· OSTI ID:22689231

Zhang, Aijie ^[1]; Jia, Yongming ^[1]; Xu, Qinghan ^[1]; Wang, Changyuan ^[1]; Liu, Qi ^[1]; Meng, Qiang ^[1]; Peng, Jinyong ^[1]; Sun, Huijun ^[1]; Sun, Pengyuan ^[1]; others, and

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1. Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University (China)

Alpha-naphthylisothiocyanate (ANIT) is a toxicant that is widely used in rodents to model human intrahepatic cholestasis. The aim of the study is to investigate whether effects of dioscin on ANIT-induced cholestasis are related to changes in expression of hepatic transporters in rats. Effects of dioscin on cholestasis were examined by histology and biochemical marker levels. The functional changes of hepatic transporters were determined by in vitro, in situ and in vivo. qRT-PCR and western blot were used to assess the expression of hepatic transporters in cholestatic rats. Dioscin administration could ameliorate cholestasis, as evidenced by reduced biochemical markers as well as improved liver pathology. The uptakes of organic anion transporting polypeptide (Oatp) substrates were altered in liver uptake index in vivo, perfused rat liver in situ and isolated rat hepatocytes in vitro in cholestasis rats. qRT-PCR and western blot analysis indicated co-treatment of ANIT with dioscin prevented the adaptive down-regulation of Oatp1a1, 1b2, and prompted the up-regulation of Oatp1a4, multidrug resistance-associated protein (Mrp) 2 and bile salt export pump (Bsep). In addition, concerted effects on Mrp2 and Bsep occurred through up-regulation of small heterodimer partner by activating farnesoid X receptor. Dioscin might prevent impairment of hepatic function by restoring hepatic transporter expression. - Highlights: • Cholestasis was improved by dioscin via up-regulating the expression of Oatps, Mrp2 and Bsep. • Dioscin regulated Mrp2 and Bsep via activating FXR. • Dioscin may be a candidate drug for the prevention of intrahepatic cholestasis.

• OSTI ID: 22689231
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Vol. 305; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ALANINES
AMINOTRANSFERASES
ANIONS
BILE
BILIRUBIN
CHAIN REACTIONS
DRUGS
ESTRONE
HISTOLOGY
IN VITRO
IN VIVO
LIQUID COLUMN CHROMATOGRAPHY
LIVER
LIVER CELLS
MASS SPECTROSCOPY
PATHOLOGY
POLYMERASE CHAIN REACTION
POLYMERASES
POLYPEPTIDES
RATS
RECEPTORS
SALTS
SODIUM
SODIUM IONS
SULFATES