Integrated analysis of transcriptomics and metabonomics profiles in aflatoxin B1-induced hepatotoxicity in rat

被引:67
作者
Lu, Xiaoyan [1 ]
Hu, Bin [1 ]
Shao, Li [1 ]
Tian, Yu [1 ]
Jin, Tingting [1 ]
Jin, Yachao [1 ]
Ji, Shen [2 ]
Fan, Xiaohui [1 ]
机构
[1] Zhejiang Univ, Pharmaceut Informat Inst, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China
[2] Shanghai Inst Food & Drug Control, Dept Tradit Chinese Med, Shanghai 201203, Peoples R China
基金
中国国家自然科学基金;
关键词
Aflatoxin B1; Transcriptomics; Metabonomics; Acute hepatotoxicity; Integrated analysis; Potential biomarkers; PYRUVATE-KINASE ACTIVITY; OXIDATIVE STRESS; IN-VIVO; LIVER; GENE; TOXICITY; EXPRESSION; BIOMARKERS; TOXICOLOGY; INDUCTION;
D O I
10.1016/j.fct.2013.01.020
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
The aim of this work was to identify mechanisms and potential biomarkers for predicting the development and progression of aflatoxin B1 (AFB1)-induced acute hepatotoxicity. In this study, microarray analysis and metabolites profiles were used to identify shifts in gene expression and metabolite levels associated with the affected physiological processes of rats treated with AFB1. Histopathological examinations and serum biochemical analysis were simultaneously performed; the results indicated that hepatotoxicity occurred in higher dosage groups. However, gene expression analysis and metabolite profiles are more sensitive than general toxicity studies for detecting AFB1-induced acute hepatotoxicity as the patterns of low-dose AFB1-treated rats in these two technique platforms were more similar to the rats in higher dosage groups than to the control rats. Integrated analysis of the results from general toxicity studies, transcriptomics and metabonomics profiles suggested that p53 signaling pathway induced by oxidative damage was the crucial step in AFB1-induced acute hepatotoxicity, whereas gluconeogenesis and lipid metabolism disorder were found to be the major metabolic effects after acute AFB1 exposure. The genes and metabolites significantly affected in common in rat liver or serum of three doses AFB1 treatments served as potential biomarkers for detecting AFB1-induced acute hepatotoxicity. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码:444 / 455
页数:12
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