A possible but unrecognized risk of acceptable daily intake dose triazole pesticides exposure—bile acid disturbance induced pharmacokinetic changes of oral medication. (May 2023)

• Record Type: Journal Article
• Authors: Xu, Yujing; Zhang, Yufeng; Tao, Quan; Sun, Quanwei; Zheng, Yuyu; Yin, Dengke; Yang, Ye
• Is Part Of: Chemosphere. Volume 322(2023)
• Publication Date: 2023-05
• Subjects: Tebuconazole -- Intestinal microenvironment -- Cytochrome P450 enzyme system -- Bile acids -- Drug absorption; ADI acceptable daily intake -- BAs bile acids -- CYPs cytochrome P450 enzymes -- CYP7A1 cholesterol 7α-hydroxylase -- CYP27A1 27-hydroxylase -- FITC fluorescein isothiocyanate -- FVS fluvastatin -- GC glycocholic acid -- GCDC glycochenodeoxycholic acid -- NR nile red -- PR phenol red -- PVS pravastatin -- RB rhodamine B -- SVS simvastatin -- TC taurocholic acid -- TDC taurodeoxycholic acid -- TEB tebuconazole; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2023.138209
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: Triazole antifungal pesticides work by inhibiting the activity of lanosterol-14-α-demethylase, a member of cytochrome 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. Graphical abstract: Image 1 Highlights: Acceptable daily intake dose triazoles exposure can lead bile acids (BAs) disturbance. BAs disturbance remarkably changes the oral absorption behavior of lipophilic drugs. It may increase additional risk for elderly and chronically ill groups. We should be more alert about the hazard of pesticide residues.