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Metabolism of N-Methyl-2-Pyrrolidone in Honey Bee Adults and Larvae: Exploring Age Related Differences in Toxic Effects
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2017-09-20 00:00:00 , DOI: 10.1021/acs.est.7b03291 Julia D. Fine 1 , Christopher A. Mullin 1
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2017-09-20 00:00:00 , DOI: 10.1021/acs.est.7b03291 Julia D. Fine 1 , Christopher A. Mullin 1
Affiliation
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In chronic feeding assays, the common agrochemical inert formulant N-methyl-2-pyrrolidone (NMP) is at least 20 times more toxic to honey bee larvae than to adults, but the underlying cause of this difference is unknown. In other taxa, NMP is primarily detoxified via a cytochrome P450 mediated pathway. Using a LC-MS method, putative cytochrome P450 metabolites of NMP were identified and quantified in adults and larvae following chronic exposure to NMP. Major differences in the identities and quantities of the generated metabolites were observed between adults and larvae. One major difference was the higher percentage of the administered NMP recovered as the parent compound in larvae compared to adults. To further explore the apparent difference in metabolic capacity, a spectrofluorometric method was used to compare general cytochrome P450 enzyme activity by monitoring the transformation of a 7-ethoxycoumarin substrate. Higher microsomal levels of 7-ethoxycoumarin-O-deethylase activity in adult fat bodies suggests that the higher percentage of unmetabolized NMP in larvae relative to adults may be due to lower cytochrome P450 enzyme activity in fat bodies. Taken together, these results suggest that larvae may be less able to detoxify xenobiotics encountered in diet than adults, and these findings will help inform future risk assessment.
中文翻译：
N-甲基-2-吡咯烷酮在蜜蜂成虫和幼虫中的代谢：探索与年龄相关的毒性作用差异
在长期饲喂试验中，常见的农用化学惰性配方N-甲基-2-吡咯烷酮（NMP）对蜜蜂幼虫的毒性至少是对成年人的20倍，但这种差异的根本原因尚不清楚。在其他分类单元中，NMP主要通过细胞色素P450介导的途径排毒。使用LC-MS方法，在成人和幼虫长期暴露于NMP后，鉴定并定量了NMP的假定细胞色素P450代谢产物。在成虫和幼虫之间观察到主要的差异，在生成的代谢产物的身份和数量上。一个主要区别是与成人相比，幼虫中作为母体化合物回收的施用NMP的百分比更高。为了进一步探讨新陈代谢能力的明显差异，使用荧光光谱法通过监测7-乙氧基香豆素底物的转化来比较一般的细胞色素P450酶活性。较高的7-乙氧基香豆素微粒体水平成年脂肪体内的O-脱乙基酶活性表明，与成年相比，幼虫中未代谢NMP的百分比更高，可能是由于脂肪体内较低的细胞色素P450酶活性所致。综上所述，这些结果表明，幼虫对饮食中所遇到的异生物的排毒能力可能不如成人，这些发现将有助于为将来的风险评估提供依据。
更新日期：2017-09-20
中文翻译：
N-甲基-2-吡咯烷酮在蜜蜂成虫和幼虫中的代谢：探索与年龄相关的毒性作用差异
在长期饲喂试验中，常见的农用化学惰性配方N-甲基-2-吡咯烷酮（NMP）对蜜蜂幼虫的毒性至少是对成年人的20倍，但这种差异的根本原因尚不清楚。在其他分类单元中，NMP主要通过细胞色素P450介导的途径排毒。使用LC-MS方法，在成人和幼虫长期暴露于NMP后，鉴定并定量了NMP的假定细胞色素P450代谢产物。在成虫和幼虫之间观察到主要的差异，在生成的代谢产物的身份和数量上。一个主要区别是与成人相比，幼虫中作为母体化合物回收的施用NMP的百分比更高。为了进一步探讨新陈代谢能力的明显差异，使用荧光光谱法通过监测7-乙氧基香豆素底物的转化来比较一般的细胞色素P450酶活性。较高的7-乙氧基香豆素微粒体水平成年脂肪体内的O-脱乙基酶活性表明，与成年相比，幼虫中未代谢NMP的百分比更高，可能是由于脂肪体内较低的细胞色素P450酶活性所致。综上所述，这些结果表明，幼虫对饮食中所遇到的异生物的排毒能力可能不如成人，这些发现将有助于为将来的风险评估提供依据。
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