cDNA Microarray Analysis and Influx Transporter OATP1B1 in Liver Cells After Exposure to Gadoxetate Disodium, a Gadolinium-based Contrast Agent in MRI Liver Imaging

cDNA微阵列分析及肝细胞暴露于钆塞酸二钠(一种用于MRI肝脏成像的钆基造影剂)后转运蛋白OATP1B1的变化

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Abstract

BACKGROUND/AIM: Gadoxetate disodium (Primovist or Eovist) is extensively used as a hepatospecific contrast agent during magnetic resonance imaging (MRI) examinations. However, there is no information determining whether gadoxetate disodium has a cytotoxic impact and/or affects relative gene expression on liver cells. In the current study, we investigated the effects of gadoxetate disodium on cytotoxicity and the levels of gene expression in human normal Chang Liver cells. MATERIALS AND METHODS: The cytotoxic effect was detected via methyl thiazolyl tetrazolium (MTT) assay and 4',6-diamidino-2-phenylindole (DAPI) staining. mRNA expression was monitored by cDNA microarray and quantitative PCR (qPCR) analysis. The protein levels were determined by western blotting. RESULTS: Gadoxetate disodium at 5 and 10 mM failed to induce any cell cytotoxicity and morphological changes in Chang Liver cells. Our data demonstrated that gadoxetate disodium significantly enhanced the expression of 29 genes and suppressed that of 27. The SLCO1C1 (solute carrier organic anion transporter family member 1C1) mRNA expression was also increased by 2.62-fold (p-value=0.0006) in gadoxetate disodium-treated cells. Furthermore, we also checked and found that gadoxetate disodium up-regulated organic anion transporter polypeptide 1B1 (OATP1B1) protein level and increased OATP uptake transporter gene SLCO1C1 mRNA expression. CONCLUSION: Our results provide evidence regarding that gadoxetate disodium might be no cytotoxic effects on liver cells.

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