1H NMR-based metabonomics study of the urinary biochemical changes in Kansui treated rat

摘要

Ethnopharmacological relevance: The dried root of Kansui (Euphorbia kansui L.) is a commonly used and effective traditional Chinese medicine (TCM). Aim of the study: We combined the urinary metabolites alteration and traditional assays of Kansui-induced rats to discuss the mechanism of toxicity of Kansui. Materials and methods: The Sprague-Dawley rats were dosed with 7.875 g Kansui/kg weight and 15.75 g Kansui/kg weight. Urine samples were collected at day -1 (before treatment), and days 7, 14 and 21 for NMR analysis. Plasma and liver and kidney tissues were collected at day 14 for biochemical assays and histopathological examination, respectively. Results: The metabonome of rats treated with Kansui differed markedly from that of the controls. This was confirmed by the histopathology of liver and kidney tissue and clinical biochemistry analysis. The toxicity of Kansui accumulated with dosing time, and persisted even when treatment was stopped. The corresponding biochemical pathways alterations included inhibited TCA cycle, increased anaerobic glycolysis, and perturbed amino acids metabolism. Conclusion: The biochemical pathways disorder conjunction with histopathology changes provides new clues to evaluate the toxicity of Kansui from a systematic and holistic view.