Assessment of amiodarone-induced phospholipidosis in chimeric mice with a humanized liver
| Autor: | Yasumi Yoshizane, Chise Tateno, Yuji Ishida, Yuka Tamura, Seigo Sanoh, Shigeru Ohta, Yaichiro Kotake, Yuto Yamachika |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Amiodarone Endogeny Pharmacology Lipidoses Toxicology 01 natural sciences Mass spectrometry imaging Mice 03 medical and health sciences chemistry.chemical_compound Species Specificity Tandem Mass Spectrometry Phosphatidylcholine medicine Animals Humans Phospholipids Phospholipidosis Transplantation Chimera Chemistry 010401 analytical chemistry 0104 chemical sciences 030104 developmental biology Liver Toxicity Hepatocytes Phosphatidylcholines Chromatography Liquid medicine.drug |
| Zdroj: | The Journal of Toxicological Sciences. 42:589-596 |
| ISSN: | 1880-3989 0388-1350 |
| DOI: | 10.2131/jts.42.589 |
| Popis: | It is important to consider susceptibility to drug-induced toxicity between animals and humans. Chimeric mice with a humanized liver are expected to predict hepatotoxicity in humans. Drug-induced phospholipidosis (DIPL), in which phospholipids accumulate, is a known entity. In this study, we examined whether chimeric mice can reveal species differences in DIPL. Changes in various phosphatidylcholine (PhC) molecules were investigated in the liver of chimeric mice after administering amiodarone, which induces phospholipidosis. Liquid chromatography-tandem mass spectrometry revealed that levels of PhCs tended to increase in the liver after administration of amiodarone. The liver of chimeric mice consists of human hepatocytes and residual mouse hepatocytes. We used imaging mass spectrometry (IMS) to evaluate the increase of PhCs in human and mouse hepatocytes after administration of amiodarone. IMS visualizes localization of endogenous and exogenous molecules in tissues. The IMS analysis suggested that the localized levels of several PhCs tended to be higher in the human hepatocytes than those in mouse hepatocytes, and PhC levels changed in response to amiodarone. Chimeric mice with a humanized liver will be useful to evaluate species differences in DIPL between mice and humans. |
| Databáze: | OpenAIRE |
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