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Table 2 Validation of potential biomarkers for cholestasis in PCLS

From: Treatment of mouse liver slices with cholestatic hepatotoxicants results in down-regulation of Fxr and its target genes

A        B       
Drug CsA CsA CsA CsA CsA MW test Drug CPZ CPZ CPZ CPZ CPZ MW test
Gene FC1 FC2 FC3 FC4 FC5   Gene FC1 FC2 FC3 FC4 FC5  
ABCG5 −3.5 −1.8 −1.0 −1.3 −1.2 NS ABCG5 −4.2 −2.9 −6.7 −3.8 1.0 *
ABCG8 −4.9 −3.9 −1.2 −2.0 −1.2 * ABCG8 −2.9 −2.1 −5.4 −4.5 −1.1 *
BAAT −5.2 −4.2 −1.6 −2.2 −1.7 * BAAT −2.3 −3.3 −8.5 −6.4 1.4 *
KLF15 −1.2 −1.7 −2.0 −1.4 −1.3 * KLF15 −2.0 −1.8 −3.2 −1.8 1.6 *
C        D       
Drug A A A A A MW test Drug VA VA VA VA VA MW test
Gene FC1 FC2 FC3 FC4 FC5   Gene FC1 FC2 FC3 FC4 FC5  
ABCG5 1.2 −1.6 1.2 1.1 −1.3 NS ABCG5 2.0 −1.7 −1.1 1.4 1.6 NS
ABCG8 2.0 −1.6 1.1 1.1 −1.1 NS ABCG8 2.2 −1.5 −1.3 1.4 1.9 NS
BAAT 1.8 −2.2 1.1 −1.0 −1.7 NS BAAT 1.3 1.0 −2.0 1.4 2.5 NS
KLF15 2.6 −1.8 −1.5 −1.4 −1.3 NS KLF15 1.0 −1.9 −1.7 −1.1 1.1 NS
E        F       
Drug ISND ISND ISND ISND ISND MW test Drug PQ PQ PQ PQ PQ MW test
Gene FC1 FC2 FC3 FC4 FC5   Gene FC1 FC2 FC3 FC4 FC5  
ABCG5 2.0 3.0 1.1 2.0 2.0 * ABCG5 1.1 1.1 1.7 −1.3 −1.6 NS
ABCG8 2.1 2.8 1.0 2.3 1.9 NS ABCG8 1.0 −1.2 1.8 −1.3 −1.4 NS
BAAT 1.8 1.7 1.1 −1.3 1.3 NS BAAT −1.2 −1.0 1.7 1.1 −1.4 NS
KLF15 1.2 2.4 1.0 1.1 1.2 NS KLF15 1.3 −1.0 1.3 1.1 −1.2 NS
  1. PCLS were exposed for 24 hours to model toxicants for cholestasis (cyclosporin A (CsA)-A, chlorpromazine (CPZ)-B), necrosis (isoniazid (ISND)-C, paraquat (PQ)-D), and steatosis (amiodarone (A)-E, valproic acid (VA)-F). Q-PCR was used to measure mRNA expression relative to actin β of four potential biomarkers: Abcg5, Abcg8, Baat, and Klf15. FC stands for fold change (treatment vs. control). Q-PCR was performed for liver slices obtained from five biological replicates. Asterisk (*) indicates significantly different gene expression (P < 0.05) from controls according to Mann–Whitney-test (MW). NS stands for not significant.