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A new amidoxime small molecule compound was synthesized by oximation addition reaction and the uranium decorporation was evaluated. The changes of endogenous metabolites caused by Uranium decorporation in animals were investigated by metabonomics method, and the related differential metabolites were searched for and their metabolic pathways and mechanisms were explored.The mice were divided into blank group (NG), model group (MG), 0.42 mmol/kg ZnNa3-DTPA group(YG), 0.21 mmol/kg amidoxime group (CN) and 0.42 mmol/kg amidoxime group (EN), and were injected with positive drug (ZnNa3-DTPA) and amidoxime compounds in tail vein immediately after the tail vein injection of uranyl acetate and amidoxme compound,the uranium content in the kidney and femur of mice was determined by Inductively-coupled plasma mass spectrometer(ICP-MS) 24 h later. The metabolites in the serum of each group were identified by GC-MS(gas chromatograaphy-mss spectrometer), and screened as potentially differentiated metabolites by orthogonal partial least squares discriminant analysis (OPLS-DA) with variable importance in the projection (VIP) > 1, mass spectrometry database and MetaboAnalyst platform were used to analyze the differential metabolites and their associated pathways. The results show that compared with model group, 0.42 mmol/kg amidoxime compound group decreased uranium content in kidney and femur by 61.70% and 54.74%, and the positive group at the same dose reduced the uranium content in kidney and femur by 60.70% and 40%, respectively.The results indicated that the small molecule compound of aminoxime had significant uranium decorporation. Metabolomic analysis showed that the metabolic profile of the amidoxime group was significantly different from that of the model group, which was closer to that of the normal group than that of the positive group. A total of 14 different metabolites were found after screening, and the enrichment analysis of metabolic pathways showed that the metabolic pathways related to them were mainly tyrosine metabolism. Biosynthesis of phenylalanine, tyrosine and tryptophan, metabolism of glycine, serine and threonine, etc. The small molecule amidoxime compound has a remarkable uranium decorporation effect, which is better than ZnNa3-DTPA, and has a protective effect on kidney injury caused by uranium.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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