A glycyrrhizin-containing preparation reduces hepatic steatosis induced by hepatitis C virus protein and iron in mice.

Abstract

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.

• Authors: Masaaki Korenaga, Isao Hidaka, Sohji Nishina, Aya Sakai, Akane Shinozaki, Toshikazu Gondo, Takakazu Furutani, Hiroo Kawano, Isao Sakaida, Keisuke Hino
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 31 Issue 4 Pg. 552-60 (Apr 2011) ISSN: 1478-3231 [Electronic] United States
• PMID: 21382166 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 John Wiley & Sons A/S.

Chemical References

• DNA Primers
• Drug Combinations
• Iron, Dietary
• Reactive Oxygen Species
• Sterol Regulatory Element Binding Protein 1
• Glycyrrhizic Acid
• stronger neominophagen C
• Iron
• Cysteine
• Glycyrrhetinic Acid
• Glycine

Topics

• Animals
• Cysteine (administration & dosage, chemistry, therapeutic use)
• DNA Primers (genetics)
• Dose-Response Relationship, Drug
• Drug Combinations
• Fatty Liver (drug therapy, etiology)
• Glycine (administration & dosage, chemistry, therapeutic use)
• Glycyrrhetinic Acid (administration & dosage, analogs & derivatives, chemistry, therapeutic use)
• Glycyrrhizic Acid (administration & dosage, chemistry, therapeutic use)
• Hepatitis C (complications)
• Immunoblotting
• Iron (metabolism)
• Iron, Dietary
• Liver (metabolism, ultrastructure)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Microscopy, Electron, Transmission
• Mitochondria (drug effects)
• Oxidative Stress (drug effects)
• Reactive Oxygen Species (metabolism)
• Statistics, Nonparametric
• Sterol Regulatory Element Binding Protein 1 (metabolism)