Balance between oxidative damage and proliferative potential in an experimental rat model of CCl4–induced cirrhosis: Protective role of adenosine administration
Balance between oxidative damage and proliferative potential in an experimental rat model of CCl4–induced cirrhosis: Protective role of adenosine administration
复制标题
DOI：
10.1002/hep.510260503
复制
发表时间：
1997-11
期刊：
影响因子：
13.5
通讯作者：
Rolando Hernández;Muñoz;M. Díaz;Verónica López;F. López;Barrera;L. Yáñez;S. Vidrio;Alberto Aranda;Fraustro;V. C. Sánchez
中科院分区：
文献类型：
--
作者：
Rolando Hernández;Muñoz;M. Díaz;Verónica López;F. López;Barrera;L. Yáñez;S. Vidrio;Alberto Aranda;Fraustro;V. C. Sánchez
氧化应激及其随后的脂质过氧化（LP）产生有害影响，目前已参与四氯化碳诱导的肝硬化的产生。然而，最近的报告表明，“生理性”LP可能与肝再生（LR）有关，因此有必要区分氧化应激诱导的LP和LR相关的LP。在连续给予CCl4 4 4周的大鼠中，发现中度细胞坏死和细脂肪浸润。组织学异常伴随着LP增加，主要由微粒体和胞质组分和氧化应激的证据（肝脏谷胱甘肽含量降低以及黄嘌呤氧化酶和戊糖磷酸途径活性的变化）。8周后，出现小结节性肝硬化，但氧化应激大大减弱，仅持续存在于微粒体中的增强型LP。同时给予腺苷（一种可靠的保肝药，可轻松预防肝纤维化的发生）能够阻断长期CCl4治疗诱导的氧化应激，但引起LP增加的选择性亚细胞分布，与LR期间发现的相似。腺苷诱导的肝脏LP变化（主要在核部分）与胸苷激酶活性增加相关。因此，数据表明，腺苷介导的能量可用性和线粒体功能的保护可能参与预防糖尿病大鼠氧化应激的发生。后者可以诱导成功的肝脏恢复，减少导致纤维化的事件序列。
Oxidative stress and its consequent lipid peroxidation (LP) exert harmful effects, which have been currently involved in the generation of carbon tetrachloride‐induced cirrhosis. However, the recent report that “physiological” LP can be associated with liver regeneration (LR) makes it necessary to discriminate between oxidative stress‐induced and LR‐associated LP. In rats rendered cirrhotic by continuous CCl4 administration for 4 weeks, moderate cell necrosis and fine fatty infiltration were found. The histological abnormalities were accompanied by increased LP, mainly accounted for by the microsomal and cytosolic fractions and evidence of oxidative stress (decreased hepatic glutathione content and changes in xanthine oxidase and pentose phosphate pathway activities). After 8 weeks, a micronodular cirrhosis developed, but oxidative stress was greatly attenuated, only persisting in the enhanced LP confined to microsomes. Simultaneous administration of adenosine, a reliable hepatoprotector that readily prevents the onset of liver fibrosis, was able to block the oxidative stress induced by the long‐term CCl4 treatment but elicited a selective subcellular distribution of increased LP, similar to that found during LR. The adenosine‐induced changes in liver LP (mainly in the nuclear fraction) correlated with an increased activity of thymidine kinase. Therefore, data suggest that adenosine‐mediated preservation of energy availability and mitochondrial function could participate in preventing the onset of oxidative stress in cirrhotic rats. The latter could induce a successful liver recovery, curtailing the sequence of events leading to fibrogenesis.