1H NMR-based Metabolomics to Study Repeated Exposure to Maleic Acid in Rats
| Autor: | Chi-Hung Chen, 陳祈宏 |
|---|---|
| Rok vydání: | 2016 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 104 More and more food safety issues are noticed by the public. In 2013, the Ministry of Health and Welfare (MOHW) in Taiwan declared that some starch-processed foods were illegally added food addictive, maleic acid/maleic anhydride. Modified starch can enhance favorable properties, such as viscosity, texture, and elasticity in food. Accidental consumption of maleic acid at low levels does not cause significant adverse health effects; however, long term exposure of high levels of maleic acid can induce kidney damage. The molecular effects of repeated maleic acid exposure are still largely unknown. In this study, we intend to understand metabolic effects of repeated exposure to maleic acid in rats using 1H NMR-based metabolomic approach. Rat urinary metabolome were examined to study time-course and dose-response of maleic acid. Adult male Sprague-Dawley (SD) rats were divided into control, low-dose (6 mg/kg), medium-dose (20 mg/kg), and high-dose (60 mg/kg) and treated with vehicle or maleic acid via oral gavage daily. Urine samples were collected twice a day (once during daytime and once at night) on day 0, 7, 14, 21, and 28 and then examined by high-resolution 1H nuclear magnetic resonance (NMR) followed by multivariate statistical analysis. The principle component analysis (PCA) score plots from the anlaysis of urinalry metabolome showed changes of metabolome patterns within different exposure groups. Clear metabolome seperation between high-dose and the control groups were observed from the night samples of day 14 and later. The increased levels of acetoacetate and hippurate, and decreased levels of alanine and acetate in the treatment groups were observed in the night samples of day 28. Changes of metabolites are related with environment stress and energy metabolism. Metabolic effects of maleic acid exposure are obvious on rats in high dose group and at last time points. By investigating the perturbation of urinary metabolome in SD rats can assist urinary biomarker discovery for maleic acid and find out possible toxic mechanisms induced by maleic acid. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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