Increased hepatic acylcarnitines after oral administration of amiodarone in rats

Amiodarone is known to induce hepatic injury in some recipients. We applied an untargeted metabolomics approach to identify endogenous metabolites with potential as biomarkers for amiodarone‐induced liver injury. Oral amiodarone administration for 1 week in rats resulted in significant elevation of...

Full description

Saved in:
Bibliographic Details
Published in:Journal of applied toxicology 2020-07, Vol.40 (7), p.1004-1013
Main Authors: Kim, Gabin, Choi, Hyung‐Kyoon, Lee, Hwanhui, Moon, Kyoung‐Sik, Oh, Jung Hwa, Lee, Jaeick, Shin, Jae Gook, Kim, Dong Hyun
Format: Article
Language:English
Subjects:
acylcarnitine
Amiodarone
Biomarkers
Energy metabolism
Gene expression
Glucose
Glucose metabolism
Hepatotoxicity
LC/MSMS
Liver
Metabolism
Metabolites
Metabolomics
Mitochondria
Oral administration
Perturbation
Phospholipids
Serum levels
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Amiodarone is known to induce hepatic injury in some recipients. We applied an untargeted metabolomics approach to identify endogenous metabolites with potential as biomarkers for amiodarone‐induced liver injury. Oral amiodarone administration for 1 week in rats resulted in significant elevation of acylcarnitines and phospholipids in the liver. Hepatic short‐ and medium‐chain acylcarnitines were dramatically increased in a dose‐dependent manner, while the serum levels of these acylcarnitines did not change substantially. In addition, glucose levels were significantly increased in both the serum and liver. Gene expression profiling showed that the hepatic mRNA levels of Cpt1, Cpt2, and Acat1 were significantly suppressed, whereas those of Acot1, Acly, Acss2, and Acsl3 were increased. These results suggest that hepatic acylcarnitines and glucose levels might be increased due to disruption of mitochondrial function and suppression of glucose metabolism. Perturbation of energy metabolism might be associated with amiodarone‐induced hepatotoxicity. Increases in hepatic short‐, medium‐ and long chain acylcarnitines and glucose levels were observed in rats after oral treatment of amiodarone. Also, hepatic mRNA levels of Cpt1, Cpt2, and Acat1 were significantly suppressed whereas those of Acot1, Acly, Acss2 and Acsl3 were increased. These results might be due to the perturbation of mitochondrial function, leading to amiodarone‐induced hepatotoxicity.
ISSN:0260-437X
1099-1263
DOI:10.1002/jat.3960