In utero exposure of female CD-1 mice to AZT and/or 3TC: II. Persistence of functional alterations in cardiac tissue.
In utero exposure of female CD-1 mice to AZT and/or 3TC: II. Persistence of functional alterations in cardiac tissue.
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DOI：
10.1007/s12012-010-9065-z
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发表时间：
2010-06
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.;Divi, Rao L.;Walker, Dale M.;McCash, Consuelo L.;Carter, Meghan M.;Campen, Matthew J.;Einem, Tracey L.;Chu, Yvonne;Seilkop, Steven K.;Kang, Huining;Poirier, Miriam C.;Walker, Vernon E.
关键词：
为了描述在子宫内暴露于常用核苷类似物（nrti）的小鼠心脏中线粒体/心肌细胞完整性和功能的时间变化，CD-1小鼠在妊娠12-18天内暴露于80 mg AZT/kg、40 mg 3TC/kg、80 mg AZT/kg加40 mg 3TC/kg或单独的载体，并在产后13周和26周检查雌性小鼠后代的心脏。评估nrti暴露小鼠心脏线粒体DNA （mtDNA）含量、氧化磷酸化（OXPHOS）酶活性、mtDNA突变和超声心动图的变化，并将其与暴露于车辆的对照小鼠的结果进行比较。一项杂交捕获-化学发光试验显示，产后13周和26周，暴露于AZT和AZT/ 3tc的小鼠心脏mtDNA水平显著增加了两倍，与暴露于车辆的小鼠相比，线粒体数量随着时间的推移几乎增加了一倍。产后13周和26周的超声心动图测量显示，与对照组相比，暴露于nrti的小鼠左心室后壁逐渐变薄，到26周时差异具有统计学意义。总的来说，在子宫内NRTI暴露几个月后，小鼠线粒体和心脏组织发生进行性功能变化；与单独使用任何一种药物相比，AZT和3TC协同作用可引起AZT/3TC的累加性心脏毒性作用。
To delineate temporal changes in the integrity and function of mitochondria/cardiomyocytes in hearts from mice exposed in utero to commonly used nucleoside analogs (NRTIs), CD-1 mice were exposed in utero to 80 mg AZT/kg, 40 mg 3TC/kg, 80 mg AZT/kg plus 40 mg 3TC/kg, or vehicle alone during days 12–18 of gestation and hearts from female mouse offspring were examined at 13 and 26 weeks postpartum. Alterations in cardiac mitochondrial DNA (mtDNA) content, oxidative phosphorylation (OXPHOS) enzyme activities, mtDNA mutations, and echocardiography of NRTI-exposed mice were assessed and compared with findings in vehicle-exposed control mice. A hybrid capture-chemiluminescence assay showed significant twofold increases in mtDNA levels in hearts from AZT- and AZT/3TC-exposed mice at 13 and 26 weeks postpartum, consistent with near doubling in mitochondrial numbers over time compared with vehicle-exposed mice. Echocardiographic measurements at 13 and 26 weeks postpartum indicated progressive thinning of the left ventricular posterior wall in NRTI-exposed mice, relative to controls, with differences becoming statistically significant by 26 weeks. Overall, progressive functional changes occurred in mouse mitochondria and cardiac tissue several months after in utero NRTI exposures; AZT and 3TC acted in concert to cause additive cardiotoxic effects of AZT/3TC compared with either drug alone.
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影响因子：
158.5
作者：
Lipshultz, SE;Easley, KA;Colan, SD
通讯作者：
Colan, SD
影响因子：
11.8
作者：
Giaquinto, C;Ruga, E;Horban, A
通讯作者：
Horban, A
影响因子：
3.8
作者：
McComsey, G;Tan, DJ;Wong, LJ
通讯作者：
Wong, LJ
DOI：
10.1097/00126334-200204150-00009
发表时间：
2002-04-15
期刊：
JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
影响因子：
--
作者：
Cooper, ER;Charurat, M;Blattner, W
通讯作者：
Blattner, W
影响因子：
3.8
作者：
Olivero, OA;Shearer, GM;Poirier, MC
通讯作者：
Poirier, MC