- 作者：Elena Zamara ; Sara Galastri ; Sara Aleffi ; Ilaria Petrai ; Manuela Aragno ; Raffaella Mastrocola ; Erica Novo ; Cristiana Bertolani ; Stefano Milani ; Francesco Vizzutti ; et al.
- 刊名：Journal of Hepatology
- 出版年：2007
- 期刊代码：162_01688278
- 类别：med
- 出版时间：February 2007
- 卷：46
- 期：2
- 页码：230-238
- 文件大小：850 K
Background/Aims
Administration of carbon tetrachloride determines liver injury, inflammation and oxidative stress, but the molecular mechanisms of damage are only partially understood. In this study, we investigated the development of acute toxic damage in mice lacking monocyte chemoattractant protein-1 (MCP-1), a chemokine which recruits monocytes and activated lymphocytes.Methods
Mice with targeted deletion of the MCP-1 gene and wild type controls were administered a single intragastric dose of carbon tetrachloride. Serum liver enzymes, histology, expression of different chemokines and cytokines, and intrahepatic levels of oxidative stress-related products were evaluated.
Results
Compared to wild type mice, peak aminotransferase levels were significantly lower in MCP-1-deficient animals. This was paralleled by a delayed appearance of necrosis at histology. In addition, MCP-1-deficient mice showed a shift in the pattern of infiltrating inflammatory cells, with a predominance of polymorphonuclear leukocytes. Lack of MCP-1 was also accompanied by reduced intrahepatic expression of cytokines regulating inflammation and tissue repair. The increase in tissue levels of reactive oxygen species and 4-hydroxy-nonenal following administration of the hepatotoxin was also significantly lower in animals lacking MCP-1.
Conclusions
Lack of MCP-1 affords protection from damage and development of oxidative stress in a toxic model of severe acute liver injury.