Natarajan Sathish Kumar, Thomas Simmy, Ramamoorthy Prabhu, Basivireddy Jayasree, Pulimood Anna B, Ramachandran Anup, Balasubramanian Kunissery A
Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India.
J Gastroenterol Hepatol. 2006 Jun;21(6):947-57. doi: 10.1111/j.1440-1746.2006.04231.x.
BACKGROUND/AIMS: Oxidative stress has been implicated in liver cirrhosis. Carbon tetrachloride and thioacetamide are the most widely used models to develop cirrhosis in rats and the present study compares oxidative stress in the liver induced by these compounds at different stages of cirrhosis development.
Twice-weekly intragastric or intraperitoneal administration of carbon tetrachloride or thioacetamide, respectively, produced liver cirrhosis after 3 months. Histology, serum markers and hepatic hydroxy proline content confirmed the cirrhosis.
An increase in oxidative stress parameters was seen in mitochondria, peroxisomes and microsomes from the liver after carbon tetrachloride or thioacetamide treatment. Oxidative stress was more severe in carbon tetrachloride treated animals than thioacetamide. Mild oxidative stress was evident at 1 and 2 months of treatment and a significant increase was seen by 3 months of treatment with either compound. By this time, frank liver cirrhosis was also observed.
These results suggest that evidence of oxygen free radicals is also found early in the development of fibrosis and cirrhosis in both models.
背景/目的：氧化应激与肝硬化有关。四氯化碳和硫代乙酰胺是在大鼠中诱导肝硬化最常用的模型，本研究比较了这些化合物在肝硬化发展不同阶段诱导的肝脏氧化应激。
分别每周两次通过胃内或腹腔内给予四氯化碳或硫代乙酰胺，3个月后产生肝硬化。组织学、血清标志物和肝脏羟脯氨酸含量证实了肝硬化。
四氯化碳或硫代乙酰胺处理后，肝脏线粒体、过氧化物酶体和微粒体中的氧化应激参数增加。四氯化碳处理的动物氧化应激比硫代乙酰胺更严重。在处理1个月和2个月时轻度氧化应激明显，用任何一种化合物处理3个月时氧化应激显著增加。此时，也观察到明显的肝硬化。
这些结果表明，在两种模型中，纤维化和肝硬化发展的早期也发现了氧自由基的证据。
