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Abstract Title:

TanshinoneⅡA may alleviate rifampin-induced cholestasis by regulating the expression and function of NTCP.

Abstract Source:

Hum Exp Toxicol. 2020 Dec 14:960327120979030. Epub 2020 Dec 14. PMID: 33307820

Abstract Author(s):

Y Yang, L Liu, M Xu, X Zhang, L Wang, Q He, M Xu, X Jiang

Article Affiliation:

Y Yang

Abstract:

The Na-taurocholate cotransporting polypeptide (NTCP) acts as the major hepatic basolateral uptake system, and plays a key role in balancing bile flow. The anti-tuberculosis drugs rifampin (RFP) can affect bile flow causing liver injury, while tanshinone IIA (TAN IIA) has the effect of protecting liver. This study aimed to investigate the effects of RFP and TAN IIA on the NTCP expression and activity, and explore the potential connections. Herein, we established sandwich-cultured primary rat hepatocytes, and quantified mRNA and protein levels of NRF2 and NTCP after treatment with RFP (10, 25, or 50μM) or co-treatment with TAN IIA (5, 10, or 20 μM) for 12, 24, 48 h (n = 3). NTCP activity was assessed by measuring the initial uptake rates of known substrates taurocholate (TCA) (n = 3) after treatment with different concentrations of RFP, TAN ⅡA for 12, 24 and 48 h. We found that RFP had inhibition effects on NRF2, NTCP mRNA and protein expression, and co-administration of TAN IIA could reverse RFP inhibition. TCA cellular accumulation was significantly decreased by RFP (39.1%), and TAN IIA could significantly induce TCA uptake of NTCP (2.9-fold at 48 h). The TCA uptake activity was correlated with the NTCP mRNA expression, confirming the role of RFP or TAN IIA on NTCP expression and activity is synchronous, and we can predict NTCP activity by detecting its mRNA expression. In conclusion, our work will enrich the significance of NTCP in the liver protection, and provide theoretical basis for TAN IIA to prevent RFP induced cholestatic liver injury.

Study Type : In Vitro Study

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Sayer Ji
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