title: The plasma metabolic profiling of chronic acephate exposure in rats via an ultra-performance liquid chromatography-mass spectrometry based metabonomic method.
abstract: This study aimed to investigate the toxic effects of long-term, low-dose acephate administration on rats using ultra-performance liquid chromatography-mass spectrometry. A total of 120 male Wistar rats were randomly assigned to different groups: control; low-dose acephate (0.5 mg kg(-1) bw(-1)); middle-dose acephate (1.5 mg kg(-1) bw(-1)); and high-dose acephate (4.5 mg kg(-1) bw(-1)). The rats continuously received acephate via drinking water for 24 weeks. Rat plasma samples were collected at different time points to measure metabonomic profiles. Liver tissues were subjected to histopathological examination. The results showed that 10 metabolites in the plasma were significantly changed in the treated groups compared with those in the control group (P < 0.05 or P < 0.01). Exposure to acephate resulted in increased lysoPC (15 : 0), lysoPC (16 : 0), lysoPC (O-18 : 0), lysoPC (18 : 1(9Z)), lysoPC (18 : 0), lysoPC (20 : 4(5Z, 8Z, 11Z, 14Z)), arachidonic acid, and 12-HETE as well as decreased tryptophan and indoleacrylic acid in rat plasma. Moreover, the contents of high-density lipoprotein, low-density lipoprotein, triglyceride, total cholesterol, free fatty acids, and malondialdehyde, as well as the activities of superoxide dismutase and phospholipaseA2 in the serum, were significantly changed in the middle- and high-dose groups compared with those in the control group (P < 0.05 or P < 0.01). Histopathological examination results revealed that exposure to acephate may induce vacuolar degeneration in the liver cell cytoplasm, fat degeneration, and liver cell necrosis. These results indicated that exposure to acephate disrupted metabolism of lipids and amino acids, induced oxidative stress, caused neurotoxicity, and resulted in liver dysfunction.
authors.affiliation: Public Health College, Harbin Medical Unviersity, 194 Xuefu Road, NangangDistrict, Harbin, Heilongjiang 150081, P. R. China. xiujuan_zhao@sina.com wuyonghui777@163.com.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Hou
authors.forename: Can
authors.initials: C
authors.lastname: Cao
authors.forename: Wei
authors.initials: W
authors.lastname: Bao
authors.forename: Shuang
authors.initials: S
authors.lastname: Yang
authors.forename: Haidan
authors.initials: H
authors.lastname: Shi
authors.forename: Dongfang
authors.initials: D
authors.lastname: Hao
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Zhao
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016002:Discriminant Analysis; D005227:Fatty Acids / Q000097:blood; D054501:Group II Phospholipases A2 / Q000378:metabolism; D016018:Least-Squares Analysis; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D055432:Metabolomics; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D063088:Phosphoramides / Q000633:toxicity*; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013482:Superoxide Dismutase / Q000097:blood; D015430:Weight Gain
chemical_list: D015415:Biomarkers; D005227:Fatty Acids; D009946:Organothiophosphorus Compounds; D063088:Phosphoramides; C001969:acephate; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D054501:Group II Phospholipases A2