Metabolomics of Hydrazine-Induced Hepatotoxicity in Rats for Discovering Potential Biomarkers
Metabolic pathway disturbances associated with drug-induced liver injury remain unsatisfactorily characterized. Diagnostic biomarkers for hepatotoxicity have been used to minimize drug-induced liver injury and to increase the clinical safety. A metabolomics strategy using rapid-resolution liquid chr...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2018-01-01
|
Series: | Disease Markers |
Online Access: | http://dx.doi.org/10.1155/2018/8473161 |
id |
doaj-0ddce3f66aa44a5d92e1a138a55fd30f |
---|---|
record_format |
Article |
spelling |
doaj-0ddce3f66aa44a5d92e1a138a55fd30f2020-11-24T23:48:46ZengHindawi LimitedDisease Markers0278-02401875-86302018-01-01201810.1155/2018/84731618473161Metabolomics of Hydrazine-Induced Hepatotoxicity in Rats for Discovering Potential BiomarkersZhuoling An0Chao Li1Yali Lv2Pengfei Li3Cheng Wu4Lihong Liu5Pharmacy Department of Beijing Chao-Yang Hospital Affiliated with Beijing Capital Medical University, Beijing, ChinaPharmacy Department of the Second Artillery General Hospital of Chinese People’s Liberation Army, Beijing, ChinaPharmacy Department of Beijing Chao-Yang Hospital Affiliated with Beijing Capital Medical University, Beijing, ChinaPharmacy Department of Beijing Chao-Yang Hospital Affiliated with Beijing Capital Medical University, Beijing, ChinaPharmacy Department of the Second Artillery General Hospital of Chinese People’s Liberation Army, Beijing, ChinaPharmacy Department of Beijing Chao-Yang Hospital Affiliated with Beijing Capital Medical University, Beijing, ChinaMetabolic pathway disturbances associated with drug-induced liver injury remain unsatisfactorily characterized. Diagnostic biomarkers for hepatotoxicity have been used to minimize drug-induced liver injury and to increase the clinical safety. A metabolomics strategy using rapid-resolution liquid chromatography/tandem mass spectrometry (RRLC-MS/MS) analyses and multivariate statistics was implemented to identify potential biomarkers for hydrazine-induced hepatotoxicity. The global serum and urine metabolomics of 30 hydrazine-treated rats at 24 or 48 h postdosing and 24 healthy rats were characterized by a metabolomics approach. Multivariate statistical data analyses and receiver operating characteristic (ROC) curves were performed to identify the most significantly altered metabolites. The 16 most significant potential biomarkers were identified to be closely related to hydrazine-induced liver injury. The combination of these biomarkers had an area under the curve (AUC) > 0.85, with 100% specificity and sensitivity, respectively. This high-quality classification group included amino acids and their derivatives, glutathione metabolites, vitamins, fatty acids, intermediates of pyrimidine metabolism, and lipids. Additionally, metabolomics pathway analyses confirmed that phenylalanine, tyrosine, and tryptophan biosynthesis as well as tyrosine metabolism had great interactions with hydrazine-induced liver injury in rats. These discriminating metabolites might be useful in understanding the pathogenesis mechanisms of liver injury and provide good prospects for drug-induced liver injury diagnosis clinically.http://dx.doi.org/10.1155/2018/8473161 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhuoling An Chao Li Yali Lv Pengfei Li Cheng Wu Lihong Liu |
spellingShingle |
Zhuoling An Chao Li Yali Lv Pengfei Li Cheng Wu Lihong Liu Metabolomics of Hydrazine-Induced Hepatotoxicity in Rats for Discovering Potential Biomarkers Disease Markers |
author_facet |
Zhuoling An Chao Li Yali Lv Pengfei Li Cheng Wu Lihong Liu |
author_sort |
Zhuoling An |
title |
Metabolomics of Hydrazine-Induced Hepatotoxicity in Rats for Discovering Potential Biomarkers |
title_short |
Metabolomics of Hydrazine-Induced Hepatotoxicity in Rats for Discovering Potential Biomarkers |
title_full |
Metabolomics of Hydrazine-Induced Hepatotoxicity in Rats for Discovering Potential Biomarkers |
title_fullStr |
Metabolomics of Hydrazine-Induced Hepatotoxicity in Rats for Discovering Potential Biomarkers |
title_full_unstemmed |
Metabolomics of Hydrazine-Induced Hepatotoxicity in Rats for Discovering Potential Biomarkers |
title_sort |
metabolomics of hydrazine-induced hepatotoxicity in rats for discovering potential biomarkers |
publisher |
Hindawi Limited |
series |
Disease Markers |
issn |
0278-0240 1875-8630 |
publishDate |
2018-01-01 |
description |
Metabolic pathway disturbances associated with drug-induced liver injury remain unsatisfactorily characterized. Diagnostic biomarkers for hepatotoxicity have been used to minimize drug-induced liver injury and to increase the clinical safety. A metabolomics strategy using rapid-resolution liquid chromatography/tandem mass spectrometry (RRLC-MS/MS) analyses and multivariate statistics was implemented to identify potential biomarkers for hydrazine-induced hepatotoxicity. The global serum and urine metabolomics of 30 hydrazine-treated rats at 24 or 48 h postdosing and 24 healthy rats were characterized by a metabolomics approach. Multivariate statistical data analyses and receiver operating characteristic (ROC) curves were performed to identify the most significantly altered metabolites. The 16 most significant potential biomarkers were identified to be closely related to hydrazine-induced liver injury. The combination of these biomarkers had an area under the curve (AUC) > 0.85, with 100% specificity and sensitivity, respectively. This high-quality classification group included amino acids and their derivatives, glutathione metabolites, vitamins, fatty acids, intermediates of pyrimidine metabolism, and lipids. Additionally, metabolomics pathway analyses confirmed that phenylalanine, tyrosine, and tryptophan biosynthesis as well as tyrosine metabolism had great interactions with hydrazine-induced liver injury in rats. These discriminating metabolites might be useful in understanding the pathogenesis mechanisms of liver injury and provide good prospects for drug-induced liver injury diagnosis clinically. |
url |
http://dx.doi.org/10.1155/2018/8473161 |
work_keys_str_mv |
AT zhuolingan metabolomicsofhydrazineinducedhepatotoxicityinratsfordiscoveringpotentialbiomarkers AT chaoli metabolomicsofhydrazineinducedhepatotoxicityinratsfordiscoveringpotentialbiomarkers AT yalilv metabolomicsofhydrazineinducedhepatotoxicityinratsfordiscoveringpotentialbiomarkers AT pengfeili metabolomicsofhydrazineinducedhepatotoxicityinratsfordiscoveringpotentialbiomarkers AT chengwu metabolomicsofhydrazineinducedhepatotoxicityinratsfordiscoveringpotentialbiomarkers AT lihongliu metabolomicsofhydrazineinducedhepatotoxicityinratsfordiscoveringpotentialbiomarkers |
_version_ |
1725484744824586240 |