Enhancement of carbon tetrachloride-induced liver injury by a single dose of ethanol: proton magnetic resonance imaging (MRI) studies in vivo.
Enhancement of carbon tetrachloride-induced liver injury by a single dose of ethanol: proton magnetic resonance imaging (MRI) studies in vivo.
复制标题
单剂量乙醇增强四氯化碳诱导的肝损伤：体内质子磁共振成像（MRI）研究。
DOI：
10.1016/0925-4439(91)90009-x
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Yamashiro,S
中科院分区：
文献类型：
--
作者：
Towner,RA;Reinke,LA;Janzen,EG;Yamashiro,S
磁共振成像（MRI）和局部磁共振波谱（MRS）被用来研究单剂量的乙醇，实验前18小时，四氯化碳诱导的急性肝毒性大鼠原位的影响。1H-MRI技术检测到暴露于乙醇和CCl 4后肝小叶中心区的局部水肿。水肿的特征在于体积选择性光谱（VOSY）方法，测量乙醇和四氯化碳处理的大鼠肝脏中的水浓度增加，与对照肝脏相比。乙醇/CCl 4处理的肝脏切片的高强度区域的电子显微镜（EM）显示了显著的亚细胞变化，如颗粒内质网（ER）的碎片化，细胞质基质中形成大空泡和脂滴，线粒体广泛肿胀以及嵴破坏。在暴露于卤化碳之前，用α-苯基叔丁基硝酮（PBN）（一种自由基自旋捕获剂）预处理，发现可以减少肝脏图像中CCl 4介导的高强度区域。PBN预处理的四氯化碳暴露大鼠肝切片的电子显微镜检查显示，与对照组相比，在亚细胞组织中只有微小的可观察到的差异，例如线粒体的一些肿胀。此外，这些数据表明，乙醇可能通过增加自由基中间体的形成来增强CCl 4的肝毒性。PBN抑制四氯化碳诱导的大鼠肝脏水肿反应表明，自由基中间体，产生的代谢的四氯化碳，可能是在启动水肿的因果关系。
Magnetic resonance imaging (MRI) and localized magnetic resonance spectroscopy (MRS) were used to study the effects of a single dose of ethanol, given 18 h prior to experiments, on CCl4-induced acute hepatotoxicity in rats in situ. Localized edema in the centrilobular region of the liver, following exposure to ethanol and CCl4, was detected by1H-MRI techniques. The edema was characterized by a volume selective spectroscopy (VOSY) method, which measured an increase in water concentration from ethanol and CCl4-treated rat livers, in comparison to control livers. Electron microscopy (EM) of the high intensity regions of the ethanol/CCl4treated liver sections revealed dramatic subcellular changes such as fragmentation of the granular endoplasmic reticulum (ER), formation of large vacuoles and lipid droplets in the cytoplasmic matrix and extensive swelling of the mitochondria as well as disruption of the cristae. Pretreatment with α-phenyltert-butyl nitrone (PBN), a free radical spin trap, prior to halocarbon exposure, was found to reduce the CCl4-mediated high intensity region in the liver images. Electron microscopy of the PBN pretreated CCl4exposed rat liver sections revealed only minor observable differences in subcellular organization, such as some swelling of the mitochondria, when compared to controls. In addition, these data suggest that ethanol may potentiate CCl4hepatotoxicity by increased formation of free radical intermediates. Inhibition of the CCl4-induced edematous response in rat liver by PBN demonstrates that free radical intermediates, arising from the metabolism of CCl4, are possibly the causal factor in the initiation of the edema.