Zeng Yan, Qi Lei, Li Sifan, Hou Yurong, Xu Wei, Wang Hong, Zhao Xiujuan, Sun Changhao
Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, Heilongjiang, China 150081.
Mol Biosyst. 2014 Oct;10(10):2643-53. doi: 10.1039/c4mb00299g.
A previous study of ours has reported that chronic exposure to low-level dichlorvos (DDVP, 7.2 mg per kg bw) damages the liver, interferes with fatty acid metabolism, and disturbs the antioxidant defense system in rats. This study aims to investigate whether or not quercetin can protect against DDVP-induced toxicity through metabonomics and to elucidate the mechanism underlying this protective effect. Rats were randomly assigned into the control group, DDVP-treated group, quercetin-treated group, and quercetin plus DDVP-treated group. DDVP and quercetin were administered to the rats daily via drinking water and gavage, respectively, continuously for 90 d. The metabonomic profiles of rat plasma were analyzed using ultra-performance liquid chromatography-mass spectrometry. Finally, 11 metabolites were identified, including those of quercetin, isorhamnetin, and quercetin-3-glucuronide. The 11 metabolites showed significant changes in some treatment groups compared with the control group. Arachidonic acid, phytosphingosine, and C16 sphinganine significantly decreased while p-cresol, lysoPE (16:0/0:0), lysoPC (15:0/0:0), lysoPC (16:0/0:0), lysoPC (0:0/18:0), and tryptophan significantly increased in the DDVP-treated group compared with the control group. The tendency of the aforementioned metabolites to change was significantly ameliorated in the high-dose quercetin (50 mg per kg bw per day) plus DDVP-treated group compared with the DDVP-treated group. However, the levels of these metabolites in the high-dose quercetin plus DDVP-treated group were still significantly different from those in the control group. The results indicate that high-dose quercetin (50 mg per kg bw per day) elicits a partial protective effect on DDVP-induced toxicity. The histopathology of the liver tissues was consistent with the above results. Quercetin demonstrated regulatory effects on the metabolism of lipids and amino acids, the antioxidant defense system, etc. Therefore, increasing the daily intake of quercetin can ameliorate the toxicity induced by chronic exposure to low-level DDVP residue in food and/or water.
我们之前的一项研究报告称,长期暴露于低剂量敌敌畏(DDVP,7.2毫克/千克体重)会损害大鼠肝脏,干扰脂肪酸代谢,并扰乱其抗氧化防御系统。本研究旨在通过代谢组学研究槲皮素是否能预防DDVP诱导的毒性,并阐明这种保护作用的潜在机制。将大鼠随机分为对照组、DDVP处理组、槲皮素处理组和槲皮素加DDVP处理组。分别通过饮用水和灌胃方式每日给大鼠施用DDVP和槲皮素,持续90天。使用超高效液相色谱-质谱联用仪分析大鼠血浆的代谢组学图谱。最终,鉴定出11种代谢物,包括槲皮素、异鼠李素和槲皮素-3-葡萄糖醛酸的代谢物。与对照组相比,部分处理组中的这11种代谢物出现了显著变化。与对照组相比,DDVP处理组中花生四烯酸、植物鞘氨醇和C16鞘氨醇显著减少,而对甲酚、溶血磷脂酰乙醇胺(16:0/0:0)、溶血磷脂酰胆碱(15:0/0:0)、溶血磷脂酰胆碱(16:0/0:0)、溶血磷脂酰胆碱(0:0/18:0)和色氨酸显著增加。与DDVP处理组相比,高剂量槲皮素(50毫克/千克体重/天)加DDVP处理组中上述代谢物的变化趋势得到显著改善。然而,高剂量槲皮素加DDVP处理组中这些代谢物的水平与对照组相比仍有显著差异。结果表明,高剂量槲皮素(50毫克/千克体重/天)对DDVP诱导的毒性有部分保护作用。肝脏组织的组织病理学与上述结果一致。槲皮素对脂质和氨基酸代谢、抗氧化防御系统等具有调节作用。因此,增加槲皮素的每日摄入量可以减轻长期暴露于食物和/或水中低剂量DDVP残留所诱导的毒性。