戊唑醇低剂量暴露对大鼠胆汁酸合成的影响
Effects of Low-dose Exposure of Tebuconazole on Bile Acids Synthesis in Rats Model
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摘要: 戊唑醇作为高效三唑类杀菌剂被广泛应用于农业生产，人类可能通过食物摄取、吸入或皮肤接触等多种途径摄入环境中残留的戊唑醇。每日允许摄入量（allowable daily intake，ADI）剂量下的戊唑醇暴露不会引起人体不良反应，但戊唑醇的作用靶点细胞色素P450酶（cytochrome P450，CYP450）不但是人体多种外源性物质代谢过程中的关键酶，同时还参与多种内源性物质的合成。本研究拟以人体与动物之间剂量换算系数100建立戊唑醇ADI剂量的大鼠口服、吸入与皮肤暴露模型，通过LC-MS/MS检测戊唑醇在组织中的分布状况，HE染色考察组织形态的变化，并用总胆汁酸试剂盒检测肝脏胆汁酸的含量，分析ADI剂量戊唑醇暴露是否影响机体的胆汁酸合成能力。结果表明，各暴露模型中的戊唑醇均主要在肝肾组织中蓄集，但皮肤暴露模型中各肠段也均有戊唑醇蓄积；口服与涂布模型组的肝组织胆汁酸与对照组相比呈下降趋势但无显著性差异，吸入模型组肝组织胆汁酸与对照组相比显著下降。推测不同暴露途径对机体的胆汁酸合成能力的影响差异可能与戊唑醇的分布差异相关。上述结果提示，戊唑醇的ADI剂量暴露可能与某些胆汁合成和代谢相关的疾病的发生关联密切。Abstract: Tebuconazole, a high-efficiency triazole, is widely used in agriculture and its environmental residue is easily to be uptaken by human beings through dietary ingestion, inhalation, and skin contact. Acceptable daily intake (ADI) is a term referring to the no health-damaging amount of a substance, even under a daily-persistent exposure. Tebuconazole is an active inhibitor of cytochrome P450 (CYP450) enzymes, which are the key enzymes for the synthesis of various endogenous materials. In order to analysis the influence of ADI dose tebuconazole on bile acid synthesis, this study established a series of tebuconazole exposure rat model through ingestion, inhalation and skin contact, with a conversion factor of 100 between human being and rat, detected the tebuconazole distribution in main tissues by using LC-MS/MS, observed the morphology characteristics of tissues by HE staining, and measured the bile acid content in liver by using the total bile acid kit. The results showed that, tebuconazole was mainly accumulated in liver and kidney tissues in all the exposure models, and accumulated in all segments of intestine in the skin exposure model; the tebuconazole exposure through ingestion and skin contact led a slight decline on total bile acid contents in liver, and the inhalation model exhibited significantly decreased total bile acid content in liver than that of the control group. We presumed that the differentiated influences of tebuconazole exposure on bile acid synthesis should be related with the different tebuconazole distribution in tissues in different exposure models. These results revealed that the ADI dose tebuconazole exposure might be associated with the occurrence and development of some bile acid synthesis- and metabolism-related diseases.
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Key words:
- tebuconazole /
- rat /
- chronic toxicity /
- bile acids synthesis /
- long-term and low-dose exposure
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