Metabolism of styrene to styrene oxide and vinylphenols in cytochrome P450 2F2- and P450 2E1-knockout mouse liver and lung microsomes.
Metabolism of styrene to styrene oxide and vinylphenols in cytochrome P450 2F2- and P450 2E1-knockout mouse liver and lung microsomes.
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DOI：
10.1021/tx400305w
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发表时间：
2014-01-21
影响因子：
4.1
通讯作者：
Zheng J
中科院分区：
文献类型：
--
作者：
Shen S;Li L;Ding X;Zheng J
苯乙烯的肺毒性是由细胞色素P450依赖的代谢活化启动的。P450 2 E1和P450 2F 2是参与苯乙烯代谢的两种主要的细胞色素P450酶。当前研究的目的是使用Cyp 2 e 1和Cyp 2f 2缺失小鼠模型确定苯乙烯代谢产物（即氧化苯乙烯和4-乙烯基苯酚）的形成与苯乙烯肺毒性之间的相关性。与野生型小鼠肺微粒体相比，Cyp 2f 2缺失小鼠肺微粒体中苯乙烯乙二醇和4-乙烯基苯酚的形成显著减少。然而，在从Cyp 2 e1-null和野生型小鼠获得的肺微粒体之间观察到苯乙烯代谢产物的产生没有显著差异。用苯乙烯（6.0 mmol/kg，ip）处理基因敲除小鼠和野生型小鼠，并监测支气管肺泡灌洗液中细胞计数和LDH活性，以评价苯乙烯诱导的肺毒性。Cyp 2 e1-null小鼠显示出与野生型动物相似的对苯乙烯肺毒性的敏感性。然而，Cyp 2f 2-null小鼠对苯乙烯诱导的肺毒性具有抗性。总之，P450 2 E1和P450 2F 2都负责苯乙烯的代谢活化。后一种酶在苯乙烯诱导的肺毒性中起重要作用。氧化苯乙烯和4-乙烯基苯酚均参与苯乙烯所致肺损伤的发生发展。
Pulmonary toxicity of styrene is initiated by cytochromes P450-dependent metabolic activation. P450 2E1 and P450 2F2 are considered to be two main cytochrome P450 (CYP) enzymes responsible for styrene metabolism in mice. The objective of the current study was to determine the correlation between the formation of styrene metabolites (i.e. styrene oxide and 4-vinylphenol) and pulmonary toxicity of styrene, using Cyp2e1- and Cyp2f2-null mouse models. Dramatic decrease in the formation of styrene glycol and 4-vinylphenol was found in Cyp2f2-null mouse lung microsomes, relative to that in the wild-type mouse lung microsomes. However, no significant difference in the production of the styrene metabolites was observed between lung microsomes obtained from Cyp2e1-null and the wild-type mice. The knock–out and wild-type mice were treated with styrene (6.0 mmol/kg, ip), and cell counts and LDH activity in bronchoalveolar lavage fluids were monitored to evaluate the pulmonary toxicity induced by styrene. Cyp2e1-null mice displayed similar susceptibility to lung toxicity of styrene as the wild-type animals. However, Cyp2f2-null mice were resistant to styrene-induced pulmonary toxicity. In conclusion, both P450 2E1 and P450 2F2 are responsible for the metabolic activation of styrene. The latter enzyme plays an important role in styrene-induced pulmonary toxicity. Both styrene oxide and 4-vinylphenol are suggested to participate in the development of lung injury induced by styrene.
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影响因子：
3.9
作者：
Choudhary, D;Jansson, I;Schenkman, JB
通讯作者：
Schenkman, JB
影响因子：
4.5
作者：
Harvilchuck, Jill A.;Carlson, Gary P.
通讯作者：
Carlson, Gary P.
影响因子：
10.4
作者：
LEIBMAN K C
通讯作者：
LEIBMAN K C
DOI：
10.1124/jpet.103.062901
发表时间：
2004-04-01
影响因子：
3.5
作者：
Baldwin, RM;Jewell, WT;Buckpitt, AR
通讯作者：
Buckpitt, AR
影响因子：
1.5
作者：
Carlson, GP;Ullman, M;Snyder, PW
通讯作者：
Snyder, PW