A glycyrrhizin-containing preparation reduces hepatic steatosis induced by hepatitis C virus protein and iron in mice
Article first published online: 15 FEB 2011
© 2011 John Wiley & Sons A/S
Volume 31, Issue 4, pages 552–560, April 2011
How to Cite
Korenaga, M., Hidaka, I., Nishina, S., Sakai, A., Shinozaki, A., Gondo, T., Furutani, T., Kawano, H., Sakaida, I. and Hino, K. (2011), A glycyrrhizin-containing preparation reduces hepatic steatosis induced by hepatitis C virus protein and iron in mice. Liver International, 31: 552–560. doi: 10.1111/j.1478-3231.2011.02469.x
- Issue published online: 8 MAR 2011
- Article first published online: 15 FEB 2011
- Received 1 July 2010, Accepted 7 January 2011
- carnitine palmitoyl transferase;
- oxidative stress;
- reactive oxygen species;
- transgenic mice
Background/Aim: A European randomized trial showed biochemical effects of 6-month treatment with Stronger Neo-Minophagen C™ (SNMC), a glycyrrhizin-containing preparation, in patients with chronic hepatitis C, but its underlying mechanisms remain elusive. We reported previously that SNMC exhibits an anti-oxidative effect in hepatitis C virus (HCV) transgenic mice that develop marked hepatic steatosis with mitochondrial injury under iron overloading. Hepatic steatosis and iron overload are oxidative stress-associated pathophysiological features in chronic hepatitis C. The aim of this study was to investigate whether long-term treatment with SNMC could prevent the development of hepatic steatosis in iron-overloaded HCV transgenic mice.
Methods: C57BL/6 transgenic mice expressing the HCV polyprotein were fed an excess iron diet concomitantly with intraperitoneal injection of saline, SNMC, or seven-fold-concentrated SNMC thrice weekly for 6 months.
Results: Stronger Neo-Minophagen C™ inhibited the development of hepatic steatosis in a dose-dependent manner without affecting hepatic iron content, attenuated ultrastructural alterations of mitochondria of the liver, activated mitochondrial β-oxidation with increased expression of carnitine palmitoyl transferase I and decreased the production of reactive oxygen species in the liver in iron-overloaded transgenic mice. However, SNMC hardly affected the unfolded protein response, which post-transcriptionally activates sterol regulatory element-binding protein 1, a transcription factor involved in lipid synthesis, even though we reported previously the activation of the unfolded protein response in the same iron-overloaded transgenic mice.
Conclusions: These results suggest that SNMC prevents hepatic steatosis possibly by protecting mitochondria against oxidative stress induced by HCV proteins and iron overload.