Abstract

1. The metabolism of bifenthrin (BIF), β-cyfluthrin (CYFL), λ-cyhalothrin (CYHA), cyphenothrin (CYPH) and esfenvalerate (ESF) was studied in liver microsomes, liver cytosol and plasma from male Sprague-Dawley rats aged 90, 21 and 15 days and from adult humans. Pyrethroid metabolism was also studied with some human expressed cytochrome P450 (CYP) and carboxylesterase (CES) enzymes.

2. All five pyrethroids were metabolised by adult (90 day old) rat hepatic microsomal CYP and CES enzymes and by cytosolic CES enzymes. The pyrethroids were also metabolised by human liver microsomes and cytosol. Some species differences were observed.

3. Pyrethroid metabolism by cytosolic CES enzymes contributes to the overall hepatic clearance of these compounds.

4. CYFL, CYHA, CYPH and ESF were metabolised by rat plasma CES enzymes, whereas none of the pyrethroids were metabolised by human plasma.

5. This study demonstrates that the ability of male rats to metabolise these pyrethroids by hepatic CYP and CES enzymes and plasma CES enzymes increases with age. In all instances, apparent intrinsic clearance values were lower in 15 than in 90 day old rats.

6. All pyrethroids were metabolised by some of the human expressed CYP enzymes studied and apart from BIF were also metabolised by CES enzymes.

摘要

1. 研究了90岁的雄性Sprague-Dawley大鼠肝脏微粒体，肝细胞溶质和血浆中联苯菊酯（BIF），β-氟氰菊酯（CYFL），λ-氯氟氰菊酯（CYHA），cyphenothrin（CYPH）和依芬戊酸酯（ESF）的代谢和成年后的21天和15天。还使用某些人类表达的细胞色素P450（CYP）和羧酸酯酶（CES）酶研究了拟除虫菊酯的代谢。

2. 所有五个拟除虫菊酯均由成年（90天大）大鼠肝微粒体CYP和CES酶以及胞质CES酶代谢。拟除虫菊酯也被人肝微粒体和细胞溶质代谢。观察到一些物种差异。

3. 胞质CES酶的拟除虫菊酯代谢有助于这些化合物的整体肝清除。

4. CYFL，CYHA，CYPH和ESF由大鼠血浆CES酶代谢，而除虫菊酯均无人血浆代谢。

5. 这项研究表明，雄性大鼠通过肝脏CYP和CES酶以及血浆CES酶代谢这些拟除虫菊酯的能力随着年龄的增长而增加。在所有情况下，15天的表观内在清除率值均低于90天大的大鼠。

6. 所有拟除虫菊酯均通过某些人类表达的CYP酶代谢，除BIF外，其他CYP酶也通过CES酶代谢。