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To investigate the hepatotoxic effects and mechanisms of glyphosate using metabolomics approaches.
Forty male Kunming mice were randomly divided into control, low-dose (50 mg/kg·d), medium-dose (250 mg/kg·d),and high-dose (500 mg/kg·d) groups, with glyphosate administered orally for 30 days. The liver organ coefficients, pathological changes, and liver function parameters were measured. UPLC-MS was employed to analyze the liver metabolic profiles, and multivariate statistical methods were utilized to identify differential metabolites, followed by enrichment analysis based on the KEGG platform.
Compared to the control group, mice exposed to medium and/or high doses of glyphosate exhibited varying degrees of edema and inflammation in liver cells, along with significantly elevated serum levels of ALT, TBILI, DBILI,and GLU. Glyphosate exposure reduced the levels of nucleotide metabolites such as hypoxanthine, xanthine, and pyrimidine, as well as cellular membrane components like choline, phosphatidylcholine, and sphingosine. It also decreased the levels of vitamins such as thiamine and retinal, and amino acid metabolites including Hom vanillic acid and 4-aminobutyraldehyde.Conversely, it increased the levels of carbohydrate metabolites such as glucose-6-phosphate, fructose-1-phosphate, and ribose-1-phosphate. Furthermore, liver function indicators ALT, TBILI, and DBILI were correlated with the aforementioned metabolites.
Glyphosate exposure can damage the structure and function of liver cells in mice by affecting nucleotide metabolism, carbohydrate metabolism, amino acid metabolism, phospholipid metabolism, and vitamin metabolism.
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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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