A possible but unrecognized risk of acceptable daily intake dose triazole pesticides exposure-bile acid disturbance induced pharmacokinetic changes of oral medication

被引：4

作者：

Xu, Yujing ^{[1
]}

Zhang, Yufeng ^{[1
]}

Tao, Quan ^{[1
]}

Sun, Quanwei ^{[1
]}

Zheng, Yuyu ^{[1
]}

Yin, Dengke ^{[1
,2
,3
]}

Yang, Ye ^{[1
,2
,3
]}

机构：

[1] Anhui Univ Chinese Med, Sch Pharm, 350 Longzihu Rd, Hefei 230012, Peoples R China

[2] Anhui Prov Key Lab Pharmaceut Preparat Technol & A, Hefei 230012, Peoples R China

[3] Anhui Prov Key Lab Res & Dev Chinese Med, Hefei 230012, Peoples R China

来源：

CHEMOSPHERE | 2023年 / 322卷

基金：

中国国家自然科学基金;

关键词：

Tebuconazole; Intestinal microenvironment; Cytochrome P450 enzyme system; Bile acids; Drug absorption; ANTIFUNGAL AGENTS; TEBUCONAZOLE; FUNGICIDES; SALTS;

D O I：

10.1016/j.chemosphere.2023.138209

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

Triazole antifungal pesticides work by inhibiting the activity of lanosterol-14-alpha-demethylase, a member of cy-tochrome P450 enzymes (CYPs), but this effect is non-specific. Bile acids (BAs) are important physical surfactants for lipids absorption in intestine, and synthesized by CYPs 7A1/27A1. Thus, we presume that triazole exposure might influence the therapeutic effect or safety of oral medication through disturbing the BAs pool, even though the exposure is under an acceptable daily intake (ADI) dose. Short-and long-term of ADI dose tebuconazole (TEB) exposure animal models were established through various routes, and statins with different hydrophilic and lipophilic properties were gavaged. It exhibited that the activity of CYP7A1/27A1 was indeed inhibited but the expression was up-regulated, the BAs pool was changed either the content and the composition, and the absorption behavior of statins with strong and medium degree of lipid-solubility were significantly changed. A series of experiments performed on models of intestinal mucus, Caco-2 cell monolayer and Caco-2/HT29 co -culture system revealed that the TEB-exposure induced BAs disturbance made impacts on drug absorption in many aspects, including drug solubility and the structure of intestinal barriers. This study suggests us to be more alert about the hazard of pesticides residues for elderly and chronically ill groups.

引用

页数：11