Towner R A, Reinke L A, Janzen E G, Yamashiro S
Magnetic Resonance Imaging Facility, Ontario Veterinary College, University of Guelph, Canada.
Biochim Biophys Acta. 1991 Apr 15;1096(3):222-30. doi: 10.1016/0925-4439(91)90009-x.
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 CC14-induced acute hepatotoxicity in rats in situ. Localized edema in the centrilobular region of the liver, following exposure to ethanol and CCl4, was detected by 1H-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/CCl4 treated 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 alpha-phenyl tert-butyl nitrone (PBN), a free radical spin trap, prior to halocarbon exposure, was found to reduce the CC14-mediated high intensity region in the liver images. Electron microscopy of the PBN pretreated CCl4 exposed 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 CCl4 hepatotoxicity 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.
采用磁共振成像（MRI）和局部磁共振波谱（MRS）技术，研究在实验前18小时给予大鼠单剂量乙醇对四氯化碳（CC14）诱导的原位急性肝毒性的影响。通过1H-MRI技术检测乙醇和CCl4处理后肝脏小叶中央区域的局部水肿。采用体积选择性波谱法（VOSY）对水肿进行表征，该方法测量了乙醇和CCl4处理的大鼠肝脏与对照肝脏相比水浓度的增加。对乙醇/CCl4处理的肝脏切片高强度区域进行电子显微镜（EM）检查，发现明显的亚细胞变化，如颗粒内质网（ER）断裂、细胞质基质中形成大液泡和脂滴、线粒体广泛肿胀以及嵴破坏。发现在卤代烃暴露前用自由基自旋捕获剂α-苯基叔丁基硝酮（PBN）预处理可减少肝脏图像中CC14介导的高强度区域。与对照相比，PBN预处理的CCl4暴露大鼠肝脏切片的电子显微镜检查仅显示亚细胞组织中有一些微小的可观察到的差异，如线粒体有些肿胀。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CCl4的肝毒性。PBN对大鼠肝脏中CCl4诱导的水肿反应的抑制表明，CCl4代谢产生的自由基中间体可能是水肿发生的致病因素。
