Metabolomics analysis of urine from rats administered with long-term, low-dose acrylamide by ultra-performance liquid chromatography-mass spectrometry

Abstract

1. To study the toxic effect of chronic exposure to acrylamide (AA) at low-dose levels, we applied metabolomics approach based on ultra-performance liquid chromatography/mass spectrometry (UPLC–MS). A total of 40 male Wistar rats were randomly assigned to different groups: control, low-dose AA (0.2 mg/kg.bw), middle-dose AA (1 mg/kg.bw) and high-dose AA (5 mg/kg.bw). The rats continuously received AA via drinking water for 16 weeks. Rat urine samples were collected at different time points for measurement of metabolomic profiles.

2. Thirteen metabolites, including the biomarkers of AA exposure (AAMA, GAMA and iso-GAMA), were identified from the metabolomic profiles of rat urine. Compared with the control group, the treated groups showed significantly increased intensities of GAMA, AAMA, iso-GAMA, vinylacetylglycine, 1-salicylate glucuronide, PE (20:1(11Z)/14:0), cysteic acid, L-cysteine, p-cresol sulfate and 7-ketodeoxycholic acid, as well as decreased intensities of 3-acetamidobutanal, 2-indolecarboxylic acid and kynurenic acid in rat urine. Notably, three new candidate biomarkers (p-cresol sulfate, 7-ketodeoxycholic acid and 1-salicylate glucuronide) in rat urine exposed to AA have been found in this study.

3. The results indicate exposure to AA disrupts the metabolism of lipids and amino acids, induces oxidative stress.

• Acrylamide
• low-dose chronic exposure
• metabolomics
• NOAEL
• rat urine

Declaration of interest

The authors declared that they have no conflicts of interest in this work. Financial support from the National Natural Science Foundation of China (81573157) and the Key Laboratory of Public Health Safety (Fudan Univeristy), Ministry of Education, China (GW2015-2) are gratefully acknowledged. The laboratory of nutrition and food hygiene in Harbin Medical University is the key laboratory of Heilongjiang Province and Heilongjiang Higher Education Institutions.

Supplementary material available online

Supplementary Tables 1–6 and Figures 1–7