Premium
Stronger Neo‐Minophagen C ™ , a glycyrrhizin‐containing preparation, protects liver against carbon tetrachloride‐induced oxidative stress in transgenic mice expressing the hepatitis C virus polyprotein
Author(s) -
Hidaka Isao,
Hino Keisuke,
Korenaga Masaaki,
Gondo Toshikazu,
Nishina Sohji,
Ando Miye,
Okuda Michiari,
Sakaida Isao
Publication year - 2007
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2007.01492.x
Subject(s) - oxidative stress , malondialdehyde , glycyrrhizin , glutathione , carbon tetrachloride , liver injury , pharmacology , genetically modified mouse , chemistry , medicine , transgene , biochemistry , enzyme , organic chemistry , gene
Background/Aim: Stronger Neo‐Minophagen C ™ (SNMC), a glycyrrhizin‐containing preparation, has been used as a treatment for chronic hepatitis for more than 30 years in Japan, and shown to be effective in preventing the development of hepatocellular carcinoma in chronic hepatitis C patients, but its underlying mechanisms remain elusive. The aim of this study was to investigate if SNMC had an anti‐oxidative effect, as oxidative stress has been proposed to be one of the mechanisms of liver injury in hepatitis C virus (HCV)‐associated chronic liver diseases. Methods: The protective effect of SNMC against carbon tetrachloride (CCl 4 )‐induced liver injury was examined using transgenic mice expressing the HCV polyprotein. Results: A small dose of CCl 4 (10 μl/kg of body weight) significantly increased the serum alanine aminotransferase (ALT) level and hepatic malondialdehyde content, decreased hepatic reduced glutathione (GSH) content and induced ultrastructural alterations of hepatic mitochondria in transgenic mice, but not in nontransgenic mice. A single SNMC treatment equivalent to a clinical dose significantly restored the serum ALT level and hepatic malondialdehyde and GSH contents, attenuated the ultrastructural alterations of hepatic mitochondria, and increased mRNA expression of γ‐glutamylcysteine synthetase (γ‐GCS). Conclusions: Transgenic mice expressing the HCV polyprotein are abnormally vulnerable to oxidative stress. SNMC protects hepatocytes against CCl 4 ‐induced oxidative stress and mitochondrial injury in the presence of HCV proteins by restoring depleted cellular GSH.