Mechanism of protective action of bicyclol against CCl₄‐induced liver injury in mice

Abstract

Bicyclol is a novel synthetic drug for the treatment of chronic viral hepatitis in China. This paper reports the protective action of bicyclol against experimental liver injury in mice and its mechanism of action. Oral administration of bicyclol markedly reduced the elevated serum transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) and the hepatic morphologic changes induced by CCl(4) in mice. Mechanistic studies demonstrated that bicyclol significantly inhibited CCl(4)-induced lipid peroxidation of liver microsomes and (14)CCl(4) covalent binding to microsomal lipids and proteins in vitro, and decreased the level of the trichloromethyl free radical (*CCl(3)) generated from CCl(4) metabolism by NADPH-reduced liver microsomes. On the other hand, bicyclol neither directly inhibited the activity of ALT or AST in vitro nor affected hepatic ALT protein content in mice. These results suggest that bicyclol has remarkable hepatoprotective effects and its mechanism of action may be related to a decrease in free radical-induced damage to hepatocytes.

Chemosensitizing multiple drug resistance of human carcinoma by bicyclol involves attenuated P-glycoprotein, GST-P and Bcl-2

“…Bicyclol demonstrates effects on anti-liver injuries, anti-hepatitis B virus and anti-liver fibrosis in animal models with its clinical efficiency in treatment of chronic viral hepatitis, a tolerant and safety in long-term oral administration by preclinical toxicity studies. [3][4][5][6][7][8][9] Recently, the chemoprevention of Bicyclol against the preneoplastic lesions in rat liver induced by diethylnitrosamie (DEN) 10 is revealed (in the process of publication), consistent with the similar study of DDB for in vitro model. 11 Interestingly, as an intrinsic multiple drug resistant (MDR) model, 12 the DEN induced the expression of p-glycoprotein, the Mdr-1 gene product, in the rat hepatic preneoplastic lesions.…”

“…1A), developed from Chinese herb Fructus Schizandrae. [1][2][3] Bicyclol indicates the improvement of pharmacological efficiency and applies for the novel clinical actions with the structure reformed. Bicyclol demonstrates effects on anti-liver injuries, anti-hepatitis B virus and anti-liver fibrosis in animal models with its clinical efficiency in treatment of chronic viral hepatitis, a tolerant and safety in long-term oral administration by preclinical toxicity studies.…”

Hepatitis B patients exhibiting mild alanine aminotransferase elevation: A comparative analysis of treatment with and without Bicyclol tablets

“…Bicyclol is a liver-protective substance administered to patients with various types of liver disease. Its mechanism of action may be closely associated with free radical-scavenging properties, protection against lipid peroxidation, protection of hepatic cell membranes and mitochondrial function (12), and inhibition of inflammatory cytokines (13). It was demonstrated in experimental and clinical studies that Bicyclol decreased serum transaminase levels and resulted in improvements as observed by pathology (14)(15)(16).…”

A Sexual Dimorphism Influences Bicyclol-Induced Hepatic Heat Shock Factor 1 Activation and Hepatoprotection

“…For example, acute liver damage induced by carbon tetrachloride (Liu et al, 2005), acetaminophen (Hou et al, 2008), concanavalin A (Bao and Liu, 2009), and D-galactosamine (GalN)/lipopolysaccharide (LPS) can be ameliorated by bicyclol administration. Further studies demonstrated that bicyclol treatment resulted in hepatic activation of heat shock transcription factor 1 (HSF1), which stimulated heat shock protein (HSP) 27 and HSP70 expression Liu, 2008, 2009).…”