Du Longfei, Li Sifan, Qi Lei, Hou Yurong, Zeng Yan, Xu Wei, Wang Hong, Zhao Xiujuan, Sun Changhao
Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 194 Xuefu Road, Harbin, Heilongjiang, China 150081.
Mol Biosyst. 2014 May;10(5):1153-61. doi: 10.1039/c4mb00044g.
In previously published articles, we evaluated the toxicity of four organophosphate (OP) pesticides (dichlorvos, dimethoate, acephate, and phorate) in rats using metabonomic technology at their corresponding no observed adverse effect levels (NOAELs). The results show that a single pesticide did not elicit a toxic response. The joint toxic action of four pesticides (at their corresponding NOAELs) was evaluated by metabolomic analysis of rat plasma under experimental conditions similar to those of the four single OP pesticides. The pesticides were administered daily to rats through drinking water for 24 weeks. The mixture of four pesticides showed a joint toxic action at the NOAELs of each pesticide. The 19 metabolites were statistically significantly changed in all the treated groups compared with those in the control group (p < 0.05 or p < 0.01). Exposure to OP pesticides resulted in increased lysoPC (15 : 0/0 : 0), lysoPC (16 : 0/0 : 0), lysoPC (O-18 : 0/0 : 0), lysoPC (P-19 : 1(12Z)/0 : 0), lysoPC (18 : 1(9Z)/0 : 0), lysoPC (18 : 0/0 : 0), lysoPC (20 : 4(5Z, 8Z, 11Z, 14Z)/0 : 0), lysoPE (16 : 0/0 : 0), lysoPC (17 : 0/0 : 0), 4-pyridoxic acid, glutamic acid, glycocholic acid, and arachidonic acid, as well as decreased C16 sphinganine, C17 sphinganine, phytosphingosine, indoleacrylic acid, tryptophan, and iodotyrosine in rat plasma. The results indicate that the mixture of OP pesticides induced oxidative stress, liver and renal dysfunction, disturbed the metabolism of lipids and amino acids, and interfered with the function of the thyroid gland. The present plasma results provided complementarities with our previous metabolomic analysis of the rat urine profile exposed to a mixture of four OP pesticides, and also contributed to the understanding of the mechanism of joint toxic action.
在之前发表的文章中，我们使用代谢组学技术，在大鼠相应的未观察到有害作用水平（NOAELs）下，评估了四种有机磷（OP）农药（敌敌畏、乐果、乙酰甲胺磷和甲拌磷）的毒性。结果表明，单一农药未引发毒性反应。在与四种单一有机磷农药实验条件相似的情况下，通过对大鼠血浆进行代谢组学分析，评估了四种农药（在其相应的NOAELs下）的联合毒性作用。通过饮用水每日给大鼠施用农药，持续24周。四种农药的混合物在每种农药的NOAELs下显示出联合毒性作用。与对照组相比，所有处理组中有19种代谢物发生了统计学显著变化（p < 0.05或p < 0.01）。接触有机磷农药导致大鼠血浆中溶血磷脂酰胆碱（15 : 0/0 : 0）、溶血磷脂酰胆碱（16 : 0/0 : 0）、溶血磷脂酰胆碱（O - 18 : 0/0 : 0）、溶血磷脂酰胆碱（P - 19 : 1(12Z)/0 : 0）、溶血磷脂酰胆碱（18 : 1(9Z)/0 : 0）、溶血磷脂酰胆碱（18 : 0/0 : 0）、溶血磷脂酰胆碱（20 : 4(5Z, 8Z, 11Z, 14Z)/0 : 0）、溶血磷脂酰乙醇胺（16 : 0/0 : 0）、溶血磷脂酰胆碱（17 : 0/0 : 0）、4 - 吡哆酸、谷氨酸、甘氨胆酸和花生四烯酸增加，以及C16鞘氨醇、C17鞘氨醇、植物鞘氨醇、吲哚丙烯酸、色氨酸和碘酪氨酸减少。结果表明，有机磷农药混合物诱导了氧化应激、肝脏和肾脏功能障碍，扰乱了脂质和氨基酸代谢，并干扰了甲状腺功能。目前的血浆结果与我们之前对暴露于四种有机磷农药混合物的大鼠尿液谱的代谢组学分析相互补充，也有助于理解联合毒性作用的机制。
