In utero exposure of female CD-1 Mice to AZT and/or 3TC: I. Persistence of microscopic lesions in cardiac tissue.
In utero exposure of female CD-1 Mice to AZT and/or 3TC: I. Persistence of microscopic lesions in cardiac tissue.
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DOI：
10.1007/s12012-010-9061-3
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发表时间：
2010-03
影响因子：
3.2
通讯作者：
Walker, Vernon E.
中科院分区：
文献类型：
--
作者：
Torres, Salina M.;March, Thomas H.;Carter, Meghan M.;McCash, Consuelo L.;Seilkop, Steven K.;Poirier, Miriam C.;Walker, Dale M.;Walker, Vernon E.
关键词：
本研究旨在从光镜和电子显微镜水平描绘经胎盘暴露于常用核苷类似物(NRTI)的小鼠心脏中心肌细胞和线粒体的时间变化。CD-1孕鼠在妊娠最后7天分别给予80 mg AZT/kg、40 mg 3TC/kg、80 mg AZT/kg+40 mg 3TC/kg或单纯赋形剂，于产后13周和26周取雌性幼鼠心脏进行组织病理学和超微结构观察。利用光学显微镜和特殊染色技术，经胎盘暴露于AZT、3TC或AZT/3TC可引起显著的肌原纤维组织病理学变化；这些变化在产后13周比产后26周更为普遍。虽然大多数光镜下的病变都消失了，但有些在产后13至26周变得更加严重。经胎盘NRTI暴露还导致药物特异性的进行性改变心肌线粒体的数量和超微结构的完整性。这些光镜和电子显微镜的发现表明，在动物模型经胎盘暴露于NRTI几个月后，心肌线粒体和肌原纤维的一部分变化持续并进展，与单独使用任何一种药物相比，AZT/3TC联合暴露产生了相加的效应。
The current study was designed to delineate temporal changes in cardiomyocytes and mitochondria at the light and electron microscopic levels in hearts of mice exposed transplacentally to commonly used nucleoside analogs (NRTIs). Pregnant CD-1 mice were given 80 mg AZT/kg, 40 mg 3TC/kg, 80 mg AZT/kg plus 40 mg 3TC/kg, or vehicle alone during the last 7 days of gestation, and hearts from female mouse pups were examined at 13 and 26 weeks postpartum for histopathological or ultrastructural changes in cross-sections of both the ventricles and the interventricular septum. Using light microscopy and special staining techniques, transplacental exposure to AZT, 3TC, or AZT/3TC was shown to induce significant histopathological changes in myofibrils; these changes were more widespread at 13 weeks than at 26 weeks postpartum. While most light microscopic lesions resolved, some became more severe between 13 and 26 weeks postpartum. Transplacental NRTI exposure also resulted in progressive drug-specific changes in the number and ultrastructural integrity of cardiac mitochondria. These light and electron microscopic findings show that a subset of changes in cardiac mitochondria and myofibrils persisted and progressed months after transplacental exposure of an animal model to NRTIs, with combined AZT/3TC exposure yielding additive effects compared with either drug alone.
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影响因子：
11.8
作者：
Giaquinto, C;Ruga, E;Horban, A
通讯作者：
Horban, A
DOI：
10.1073/pnas.83.21.8333
发表时间：
1986-11-01
影响因子：
11.1
作者：
FURMAN, PA;FYFE, JA;BARRY, DW
通讯作者：
BARRY, DW
影响因子：
1.5
作者：
Gerschenson, M;Nguyen, V;Poirier, MC
通讯作者：
Poirier, MC
影响因子：
5
作者：
Lewis, W;Haase, CP;Palmieri, F
通讯作者：
Palmieri, F
影响因子：
5
作者：
Lewis, W;Haase, CP;Samarel, AM
通讯作者：
Samarel, AM