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采用超高效液相色谱-质谱联用技术对大鼠慢性低剂量敌百虫暴露的毒作用进行代谢组学分析。

Metabolomic analysis of the toxic effects of chronic exposure to low-level dichlorvos on rats using ultra-performance liquid chromatography-mass spectrometry.

机构信息

Public Health College, Harbin Medical University, Harbin 150081, PR China.

出版信息

Toxicol Lett. 2011 Oct 30;206(3):306-13. doi: 10.1016/j.toxlet.2011.08.012. Epub 2011 Aug 25.

DOI:10.1016/j.toxlet.2011.08.012
PMID:21889581
Abstract

The purpose of the current study was to assess the effects of long-term exposure to low levels of DDVP on the biochemical parameters and metabolic profiles of rats. Three different doses (2.4, 7.2, and 21.6 mg/kg body weight/day) of DDVP were administered to rats through their drinking water over 24 weeks. Significant changes in blood cholinesterase, creatinine, urea nitrogen, aspartate aminotransferase, alanine aminotransferase, and albumin concentrations were observed in the middle and high dose groups. Changes in the concentration of some urine metabolites were detected via ultra performance liquid chromatography-mass spectrometry (UPLC-MS). Dimethyl phosphate (DMP), which was exclusively detected in the treated groups, can be an early, sensitive biomarker for DDVP exposure. Moreover, DDVP treatment resulted in an increase in the lactobionic acid, estrone sulfate, and indoxyl sulfic concentrations, and a decrease in citric acid, suberic acid, gulonic acid, urea, creatinine, and uric acid. These results suggest that chronic exposure to low-level DDVP can cause a disturbance in carbohydrate and fatty acid metabolism, the antioxidant system, etc. Therefore, an analysis of the metabolic profiles can contribute to the understanding of the adverse effects of long-term exposure to low doses of DDVP.

摘要

本研究旨在评估长期低水平接触敌敌畏对大鼠生化参数和代谢谱的影响。通过饮用水,将三种不同剂量(2.4、7.2 和 21.6mg/kg 体重/天)的敌敌畏给予大鼠,持续 24 周。在中、高剂量组观察到血液胆碱酯酶、肌酐、尿素氮、天冬氨酸转氨酶、丙氨酸转氨酶和白蛋白浓度的显著变化。通过超高效液相色谱-质谱联用仪(UPLC-MS)检测到一些尿液代谢物浓度的变化。仅在处理组中检测到的磷酸二甲酯(DMP)可以作为敌敌畏暴露的早期、敏感生物标志物。此外,敌敌畏处理导致乳糖尿酸、雌酮硫酸酯和吲哚硫酸浓度增加,柠檬酸、琥珀酸、戊二酸、尿素、肌酐和尿酸浓度降低。这些结果表明,慢性低水平接触敌敌畏会导致碳水化合物和脂肪酸代谢、抗氧化系统等紊乱。因此,代谢谱分析有助于了解长期低剂量接触敌敌畏的不良影响。

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