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Changes in metabolic profiles of urine from rats following chronic exposure to anticholinesterase pesticides |
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| Authors: | Hui-Ping Wang Yu-Jie Liang Qi Zhang Ding-Xin LongWei Li Li LiLin Yang Xian-Zhong Yan Yi-Jun Wu |
| Institution: | a Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichenxi Road, Beijing 100101, PR China b Graduate School of the Chinese Academy of Sciences, Beijing 100039, PR China c National Center of Biomedical Analysis, 27 Taiping Road, Beijing 100850, PR China |
| Abstract: | Previous studies have demonstrated that the anticholinesterase pesticides chlorpyrifos and carbaryl are neurotoxic to mammals. However, the toxicity of these pesticides to other organs and their potential interactive effects remain unclear. Our goal in this study was to assess the toxicities of ingestion of chlorpyrifos and carbaryl both separately, and in combination to non-nervous systems, especially the effect on urinary metabolic profiles, in rats. Chlorpyrifos, carbaryl and a mixture of these pesticides, were administered orally to Wistar rats for 90 consecutive days. Histopathological examination of liver and kidney and metabonomic analysis based on the urinary 1H nuclear magnetic resonance spectra were used to investigate the toxic effects. The results showed that no histopathological changes were observed in the liver or kidney tissues, but metabonomic analysis revealed alternations in a number of urinary metabolites involving in the energy metabolism in liver mitochondria. Treatment of rats with chlorpyrifos alone led to an increase in creatine, glycine, dimethylglycine, dimethylamine, glutamine, succinate, alanine, lactate, and glucose. The categories of main differential urinary metabolites in carbaryl-treated rats were similar to those in chlorpyrifos-treated rats, whereas the changes were of varying degree. A combination of a low dose of chlorpyrifos and carbaryl resulted in an increase in the levels of main urinary metabolites compared to the controls, and the increase in signal intensity of the main metabolites was lower than that in the rats exposed to chlorpyrifos or carbaryl alone. All above results suggest that chronic exposure to chlorpyrifos and carbaryl alone, or in combination could cause disturbance of metabolic function in liver mitochondria and renal failure. Overall, we have shown that urine metabonomic analysis is non-invasive, sensitive, and relatively fast for assessing the individual or mutual effects following exposure to pesticides. |
| Keywords: | CAR carbaryl CPF chlorpyrifos D2O deuterium oxide DMA dimethylamine DMG dimethylglycine FIDs free induction decays NMR nuclear magnetic resonance PCA principal components analysis SIMCA soft independent modeling of class analogy TCA tricarboxylic acid TMAO trimethylamine oxide TSP 2 2&prime 3 3&prime -deuterotrimethylsilylpropionic acid |
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