Coffee and hepatocellular carcinoma: Cause or confounding?

✍ Scribed by Prachi S. Patil; Mohandas K. Mallath

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 54 KB
• Volume: 46
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.22004

✦ Synopsis

0.12 Ϯ 0.004 pg/g protein). Hence, in our animal model of NASH, RGZ treatment also seems to have some anti-inflammatory effects. Nevertheless, serum aminotransferase levels increased during treatment, and electron microscopy demonstrated unviable degenerated hepatocytes. Thus, these apparent hepatotoxic effects of RGZ on ob/ob mice might be attributed to its worsening effect on the oxidative phosphorylation, in particular, to its inhibitory effect on the complex I of the MRC. This effect has also been described by others [5][6][7] in cell cultures and liver homogenates. Furthermore, using proteomic technology, including in-gel activity assay, we confirmed that RGZ treatment markedly decreases the activity of complex I in normal mice and that the 2-dimensional SDS-PAGE system demonstrated that this complex was incompletely assembled (unpublished observations). Failure of this complex to transport electrons through the MRC results not only in a decreased oxidative phosphorylation, but also in the generation of excessive amount of superoxide anion, and consequently in oxidative stress. 8 In both rat and mouse models, there is evidence showing that RGZ increases oxidative stress (increased lipid peroxidation, tyrosine nitrated proteins, decreased mitochondrial glutathione concentrations). Therefore, this stress might contribute to hepatocyte degeneration and apoptotic cell death. The apoptotic effect of glitazones has been demonstrated by others in a variety of cells, and it seems to be mediated by the generation of reactive oxygen species. 9-11 Obviously, these cytotoxic effects do not depend on the inflammatory activity of the liver lesion.