Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing, 400715, China.
Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing, China.
Environ Sci Pollut Res Int. 2017 Aug;24(23):18870-18880. doi: 10.1007/s11356-017-9534-z. Epub 2017 Jun 26.
Endosulfan is the newly persistent organic pollutants (POPs) added to the Stockholm Convention as its widespread use, persistence, bioaccumulation, long-range transport, endocrine disruption, and toxicity related to various adverse effects. In the present study, male mice were administrated endosulfan at 0, 0.5, and 3.5 mg/kg by gavage for 2 weeks. H-NMR-based urinary metabolomics, HPLC-MS/MS-based targeted serum metabolomics, clinical analysis, and histopathology techniques were employed to evaluate the metabolic perturbations of subacute endosulfan exposure. Endosulfan exposures resulted in weight loss, liver inflammation and necrosis, and alterations in serum amino acids and urine metabolomics. Based on altered metabolites, several significantly perturbed pathways were identified including glycine, serine, and threonine metabolism; TCA cycle; pyruvate metabolism; glycolysis or gluconeogenesis; glycerophospholipid metabolism; and glyoxylate and dicarboxylate metabolism. Such pathways were highly related to amino acid metabolism, energy metabolism, and lipid metabolism. In addition, metabolomic results also demonstrated that gut microbiota was remarkably altered after endosulfan exposure. These observations may provide novel insight into revealing the potential toxic mechanism and evaluating the health risk of endosulfan exposure at metabolomic level.
硫丹是新列入《斯德哥尔摩公约》的持久性有机污染物（POPs），因其广泛使用、持久性、生物累积性、长距离迁移性、内分泌干扰和毒性而具有各种不良影响。在本研究中，雄性小鼠通过灌胃分别给予硫丹 0、0.5 和 3.5mg/kg，连续 2 周。采用基于 H-NMR 的尿代谢组学、基于 HPLC-MS/MS 的靶向血清代谢组学、临床分析和组织病理学技术，评估亚急性硫丹暴露对代谢的干扰。硫丹暴露导致体重减轻、肝脏炎症和坏死以及血清氨基酸和尿液代谢组学的改变。基于改变的代谢物，确定了几个显著受干扰的途径，包括甘氨酸、丝氨酸和苏氨酸代谢；TCA 循环；丙酮酸代谢；糖酵解或糖异生；甘油磷脂代谢；和乙醛酸和二羧酸代谢。这些途径与氨基酸代谢、能量代谢和脂质代谢密切相关。此外，代谢组学结果还表明，硫丹暴露后肠道微生物群发生了显著改变。这些观察结果可能为揭示硫丹暴露的潜在毒性机制和在代谢组学水平评估健康风险提供新的见解。
