Immunization and Drug Metabolizing Enzymes: Focus on Hepatic Cytochrome P450 3A.
Immunization and Drug Metabolizing Enzymes: Focus on Hepatic Cytochrome P450 3A.
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DOI：
10.1080/14760584.2021.1899818
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发表时间：
2021-05
影响因子：
6.2
通讯作者：
Croyle MA
中科院分区：
文献类型：
--
作者：
Jonsson-Schmunk K;Ghose R;Croyle MA
2013-2016年埃博拉疫情和2009年流感以及目前的SARS-CoV-2大流行等传染病紧急情况表明，现在可以为预先存在需要药物管理的病理的不同人群提供疫苗。许多天然生物分子（类固醇激素，脂肪酸，维生素）和约60%的处方药物是由肝细胞色素P450（CYP 1A 4）3A 4处理的。这项工作的目的是确定感染和疫苗对药物代谢的影响。在人肝细胞（HC-04细胞）和小鼠中评价了表达埃博拉糖蛋白（AdEBO）和H1N1和H3 N2流感病毒的腺病毒疫苗对肝细胞α 3A 4和相关核受体的影响。在施用小鼠适应性H1N1后24小时，小鼠中CYP 3A活性被抑制55%，而在用H1N1和H3 N2感染后，由于细胞翻译能力的全面抑制，HC-04细胞中仍保持< 10%的活性，这通过磷酸化真核翻译起始因子4 e（eIF 4 E）的减少（70%，H1N1，56%，H3 N2）来指示。感染后24小时，AdEBO抑制体内（44%）和体外（26%）CYP 3A活性。随着SARS-CoV-2和其他全球病原体疫苗临床评价的增加，有必要进行研究，以评估新疫苗和新出现的病原体对CYP 3A 4和其他代谢酶的影响，以避免在传染病紧急情况下可能进一步损害公共卫生的治疗失败。
Infectious disease emergencies like the 2013–2016 Ebola epidemic and the 2009 influenza and current SARS-CoV-2 pandemics illustrate that vaccines are now given to diverse populations with pre-existing pathologies requiring pharmacological management. Many natural biomolecules (steroid hormones, fatty acids, vitamins) and ~60% of prescribed medications are processed by hepatic cytochrome P450 (CYP) 3A4. The objective of this work was to determine the impact of infection and vaccines on drug metabolism. The impact of an adenovirus-based vaccine expressing Ebola glycoprotein (AdEBO) and H1N1 and H3N2 influenza viruses on hepatic CYP 3A4 and associated nuclear receptors was evaluated in human hepatocytes (HC-04 cells) and in mice. CYP3A activity was suppressed by 55% in mice 24h after administration of mouse adapted H1N1 while < 10% activity remained in HC-04 cells after infection with H1N1 and H3N2 due to global suppression of cellular translation capacity, indicated by reduction (70%, H1N1, 56%, H3N2) of phosphorylated eukaryotic translation initiation factor 4e (eIF4E). AdEBO suppressed CYP3A activity in vivo (44%) and in vitro (26%) 24 hours after infection. As clinical evaluation of vaccines for SARS-CoV-2 and other global pathogens rise, studies to evaluate the impact of new vaccines and emerging pathogens on CYP3A4 and other metabolic enzymes are warranted to avoid therapeutic failures that could further compromise public health during infectious disease emergencies.
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DOI：
10.1124/jpet.104.075374
发表时间：
2005-02-01
影响因子：
3.5
作者：
Callahan, SM;Ming, X;Croyle, MA
通讯作者：
Croyle, MA
影响因子：
5.4
作者：
Burgui, Idoia;Yangueez, Emilio;Nieto, Amelia
通讯作者：
Nieto, Amelia
影响因子：
4.9
作者：
Choi JH;Jonsson-Schmunk K;Qiu X;Shedlock DJ;Strong J;Xu JX;Michie KL;Audet J;Fernando L;Myers MJ;Weiner D;Bajrovic I;Tran LQ;Wong G;Bello A;Kobinger GP;Schafer SC;Croyle MA
通讯作者：
Croyle MA
影响因子：
4.8
作者：
Hodges, Erin N.;Connor, John H.
通讯作者：
Connor, John H.
影响因子：
5.4
作者：
DALY, K;NGUYEN, P;BLACKMAN, MA
通讯作者：
BLACKMAN, MA