Benoxacor is enantioselectively metabolized by rat liver subcellular fractions.
Benoxacor is enantioselectively metabolized by rat liver subcellular fractions.
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DOI：
10.1016/j.cbi.2020.109247
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发表时间：
2020-10-01
影响因子：
5.1
通讯作者：
Lehmler HJ
中科院分区：
文献类型：
--
作者：
Simonsen D;Cwiertny DM;Lehmler HJ
本研究探讨除草剂配方的一种成分苯恶唑在雌性或雄性大鼠肝脏微粒体或胞质溶胶中的对映体选择性代谢。将苯恶唑与微粒体或细胞溶质孵育≤ 30分钟，并使用气相色谱法测量其对映选择性消耗。在存在和不存在NADPH的情况下，在与活性微粒体孵育时，苯恶嗪被耗尽，表明其通过肝细胞色素P450酶（CYP）和微粒体羧酸酯酶（CES）代谢。在存在谷胱甘肽的情况下，在胞质孵育中苯氧解草胺被耗尽，这与其通过谷胱甘肽S-转移酶（GST）代谢一致。与雄性大鼠的胞质液孵育相比，苯恶唑菌酮的消耗更快，而在微粒体孵育中未观察到统计学显著的性别差异。解草唑的消耗被抑制剂1-氨基苯并三唑、CES抑制剂苯偶酰和GST抑制剂依他尼酸抑制。对苯恶菌唑内在清除率的估计表明，CYP是负责大鼠苯恶菌唑代谢的主要代谢酶。微粒体孵育显示富集了第一个洗脱的解草唑对映体（E1-解草唑）。雌鼠微粒体的富集程度（EF = 0.67 ± 0.01）大于雄鼠微粒体（EF = 0.60 ± 0.01）。雌性大鼠的胞质孵育导致E1-苯恶唑菌酮富集（EF = 0.54 ± 0.01），而雄性大鼠的胞质孵育显示第二洗脱对映体富集（E2-苯恶唑菌酮; EF = 0.43 ± 0.01）。大鼠体内苯恶唑代谢的性别差异可能会对生态风险和哺乳动物毒性产生重大影响。此外，苯恶唑的对映体富集的变化可能是环境归宿和运输研究的有力工具。
This study investigated the enantioselective metabolism of benoxacor, an ingredient of herbicide formulations, in microsomes or cytosol prepared from female or male rat livers. Benoxacor was incubated for ≤ 30 minutes with microsomes or cytosol, and its enantioselective depletion was measured using gas chromatographic methods. Benoxacor was depleted in incubations with active microsomes in the presence and absence of NADPH, suggesting its metabolism by hepatic cytochrome P450 enzymes (CYPs) and microsomal carboxylesterases (CESs). Benoxacor was depleted in cytosolic incubations in the presence of glutathione, consistent with its metabolism by glutathione S-transferases (GSTs). The depletion of benoxacor was faster in incubations with cytosol from male than female rats, whereas no statistically significant sex differences were observed in microsomal incubations. The consumption of benoxacor was inhibited by the CYP inhibitor 1-aminobenzotriazole, the CES inhibitor benzil, and the GST inhibitor ethacrynic acid. Estimates of the intrinsic clearance of benoxacor suggest that CYPs are the primary metabolic enzyme responsible for benoxacor metabolism in rats. Microsomal incubations showed an enrichment of the first eluting benoxacor enantiomer (E1-benoxacor). A greater enrichment occurred in incubations with microsomes from female (EF=0.67±0.01) than male rats (EF=0.60±0.01). Cytosolic incubations from female rats resulted in enrichment of E1-benoxacor (EF=0.54±0.01), while cytosolic incubations from male rats displayed enrichment of the second eluting enantiomer (E2-benoxacor; EF=0.43±0.01). Sex-dependent differences in the metabolism of benoxacor in rats could significantly impact ecological risks and mammalian toxicity. Moreover, changes in the enantiomeric enrichment of benoxacor may be a powerful tool for environmental fate and transport studies.
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影响因子：
2.7
作者：
IGARASHI, T;SATOH, T;KITAGAWA, H
通讯作者：
KITAGAWA, H
DOI：
10.1016/0272-0590(85)90112-5
发表时间：
1985-12-01
期刊：
FUNDAMENTAL AND APPLIED TOXICOLOGY
影响因子：
--
作者：
FONNUM, F;STERRI, SH;JOHNSEN, H
通讯作者：
JOHNSEN, H
影响因子：
6.9
作者：
Acharya, Saraswati Poudel;Johnson, Jacob;Weidhaas, Jennifer
通讯作者：
Weidhaas, Jennifer
影响因子：
3.3
作者：
Cai, Ping;Boor, Paul J.;Konig, Rolf
通讯作者：
Konig, Rolf
影响因子：
5.1
作者：
Coleman, S;Liu, SM;Rose, RL
通讯作者：
Rose, RL