Metabolomic analysis of the toxic effect of chronic low-dose exposure to acephate on rats using ultra-performance liquid chromatography/mass spectrometry

Abstract

To study the toxic effect of chronic exposure to acephate at low-dose levels, a metabolomics approach based on ultra-performance liquid chromatography/mass spectrometry (UPLC-MS) was applied. Three different doses of 0.5mg/kg/day, 1.5mg/kg/day, and 4.5mg/kg/day acephate were administered to Wistar rats for 24 weeks. Endogenous metabolite profiles were obtained with UPLC-MS for all rats at six time points after treatment. Some metabolites like dimethylthiophosphate and uric acid in urine were detected at week 4. Dimethylthiophosphate, which had the most significant elevations compared with other biomarkers, was considered as an early, sensitive biomarker of exposure to acephate. Moreover, there were some endogenous metabolite changes, which demonstrated that the doses of 1.5mg/kg/day and 4.5mg/kg/day of acephate led to renal injury and perturbed the normal metabolic processes of rats, including glucose, nucleic acid, and protein metabolism. A connection between exposure to acephate and the metabolic disturbance has been found and interpreted. Our study indicates that the metabolomics approach based on UPLC-MS of urine provides more information on toxicity than the conventional toxicological evaluation methods in measuring changes and can be considered as a promising technique for the study of the toxic effect of acephate.