Molecular and macromolecular alterations of recombinant adenoviral vectors do not resolve changes in hepatic drug metabolism during infection
Molecular and macromolecular alterations of recombinant adenoviral vectors do not resolve changes in hepatic drug metabolism during infection
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DOI：
10.1186/1743-422x-5-111
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发表时间：
2008-09-30
期刊：
影响因子：
4.8
通讯作者：
Croyle, Maria A.
中科院分区：
文献类型：
--
作者：
Callahan, Shellie M.;Wonganan, Piyanuch;Croyle, Maria A.
在本报告中，我们验证了一种假设，即长期病毒诱导的CYP改变发生在病毒引发的可能与免疫反应无关的变化中。在给雄性大鼠注射5.7 x 10(12) vp /kg的重组腺病毒后0.25、1、4和14天，研究人员对人类CYP3A4和CYP2C11的相关基因CYP3A2的酶活性、蛋白表达和mRNA进行了评估。包含所有病毒基因的野生型腺病毒在6小时内分别抑制了37%和39%的CYP3A2和2C11活性。14天后，对照组水平分别降至67% （CYP3A2）和79% （CYP2C11）
In this report we test the hypothesis that long-term virus-induced alterations in CYP occur from changes initiated by the virus that may not be related to the immune response. Enzyme activity, protein expression and mRNA of CYP3A2, a correlate of human CYP3A4, and CYP2C11, responsive to inflammatory mediators, were assessed 0.25, 1, 4, and 14 days after administration of several different recombinant adenoviruses at a dose of 5.7 x 10(12) virus particles (vp)/kg to male Sprague Dawley rats. Wild type adenovirus, containing all viral genes, suppressed CYP3A2 and 2C11 activity by 37% and 39%, respectively within six hours. Levels fell to 67% (CYP3A2) and 79% (CYP2C11) of control by 14 days (p