title: Metabonomics evaluation of urine from rats administered with phorate under long-term and low-level exposure by ultra-performance liquid chromatography-mass spectrometry.
abstract: The purpose of this study was to investigate the toxic effect of long-term and low-level exposure to phorate using a metabonomics approach based on ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Male Wistar rats were given phorate daily in drinking water at low doses of 0.05, 0.15 or 0.45 mg kg⁻¹ body weight (BW) for 24 weeks consecutively. Rats in the control group were given an equivalent volume of drinking water. Compared with the control group, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), urea nitrogen (BUN) and creatinine (CR) were increased in the middle- and high-dose groups whereas albumin (ALB) and cholinesterase (CHE) were decreased. Urine metabonomics profiles were analyzed by UPLC-MS. Compared with the control group, 12 metabolites were significantly changed in phorate-treated groups. In the negative mode, metabolite intensities of uric acid, suberic acid and citric acid were significantly decreased in the middle- and high-dose groups, whereas indoxyl sulfic acid (indican) and cholic acid were increased. In the positive mode, uric acid, creatinine, kynurenic acid and xanthurenic acid were significantly decreased in the middle- and high-dose groups, but 7-methylguanine (N⁷G) was increased. In both negative and positive modes, diethylthiophosphate (DETP) was significantly increased, which was considered as a biomarker of exposure to phorate. In conclusion, long-term and low-level exposure to phorate can cause disturbances in energy-related metabolism, liver and kidney function, the antioxidant system, and DNA damage. Moreover, more information can be provided on the evaluation of toxicity of phorate using metabonomics combined with clinical chemistry.
authors.affiliation: Public Health College, Harbin Medical University, Harbin, 150081, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zeng
authors.forename: Yurong
authors.initials: Y
authors.lastname: Hou
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Zhao
authors.forename: Changhao
authors.initials: C
authors.lastname: Sun
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood / Q000652:urine*; D001806:Blood Urea Nitrogen; D002210:Caprylates / Q000652:urine; D019826:Cholic Acid / Q000652:urine; D002802:Cholinesterases / Q000097:blood; D002853:Chromatography, Liquid; D019343:Citric Acid / Q000652:urine; D003404:Creatinine / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D003998:Dicarboxylic Acids / Q000652:urine; D004305:Dose-Response Relationship, Drug; D006147:Guanine / Q000031:analogs & derivatives / Q000652:urine; D007200:Indican / Q000652:urine; D007736:Kynurenic Acid / Q000652:urine; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics; D010702:Phorate / Q000008:administration & dosage* / Q000633:toxicity*; D010710:Phosphates / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin; D014527:Uric Acid / Q000652:urine; D014977:Xanthurenates / Q000652:urine
chemical_list: D015415:Biomarkers; D002210:Caprylates; D003998:Dicarboxylic Acids; D010710:Phosphates; D012709:Serum Albumin; D014977:Xanthurenates; D014527:Uric Acid; D019343:Citric Acid; D010702:Phorate; C028330:xanthurenic acid; D006147:Guanine; C008450:7-methylguanine; C005738:suberic acid; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002802:Cholinesterases; D019826:Cholic Acid; D007736:Kynurenic Acid; D007200:Indican; D001663:Bilirubin; C035638:thiophosphoric acid
keywords: long-term exposure; low-level exposure; metabonomics; phorate; toxic effects