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

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.

The molecular mechanism of contrast-induced nephropathy (CIN) and its link to in vitro studies on iodinated contrast media (CM).

Iodinated contrast media (iodinated CM) have increased ability to absorb x-rays and to visualize structures that normally are impossible to observe in a radiological examination. The use of iodinated CM may destory renal function, commonly known as contrast-induced nephropathy (CIN), which can result in acute renal failure (ARF). This review article mainly focuses on the following areas: (1) classifications of iodinated CM: ionic or non-ionic, high-osmolarity contrast media (HOCM), low-osmolarity contrast media (LOCM) and iso-osmolarity contrast media (IOCM); (2) an introduction to the physical and chemical properties of the non-ionic iodinated CM; (3) the management of anaphylactic reaction by iodinated CM; (4) a suggested single injection of adult doses and maximum dose for non-ionic iodinated CM; (5) the molecular mechanism of contrast-induced nephropathy (CIN); (6) In vitro studies on iodinated CM. Based on above information, this review article provide an insight for understanding the drug safety of iodinated CM.