Chi-Cheng Lu1, Wen-Kang Chen2, Jo-Hua Chiang3, Yuh-Feng Tsai4, Yu-Ning Juan5, Ping-Chin Lin6, Yeu-Sheng Tyan7,8,9, Jai-Sing Yang10. 1. Department of Pharmacy, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, R.O.C. 2. Department of Applied Cosmetology, National Tainan Junior College of Nursing, Tainan, Taiwan, R.O.C. 3. Department of Nursing, Chung Jen Catholic Junior College, Chiayi, Taiwan, R.O.C. 4. Department of Diagnostic Radiology, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, R.O.C. 5. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C. 6. Department of Medical Imaging, Chia-Yi Christian Hospital, Chiayi, Taiwan, R.O.C. 7. Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan, R.O.C. jaisingyang@gmail.com ystyan08@gmail.com. 8. School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan, R.O.C. 9. School of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C. 10. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C. jaisingyang@gmail.com ystyan08@gmail.com.
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. Copyright
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. Copyright
Authors: T Abe; M Kakyo; T Tokui; R Nakagomi; T Nishio; D Nakai; H Nomura; M Unno; M Suzuki; T Naitoh; S Matsuno; H Yawo Journal: J Biol Chem Date: 1999-06-11 Impact factor: 5.157