Bicyclol, a synthetic dibenzocyclooctadiene derivative, decreases hepatic lipids but increases serum triglyceride level in normal and hypercholesterolaemic mice

Bicyclol is used for the treatment of chronic hepatitis B in China. In this study, the effects of bicyclol (100 or 300 mg kg−1, p.o.) on serum and liver lipid contents were investigated in both normal and experimentally induced hypercholesterolaemic mice. Hypercholesterolaemia was induced by either oral administration of cholesterol/bile salt or feeding a diet containing lard/cholesterol. Daily administration of bicyclol for 7 days dose‐dependently increased the serum triglyceride level (29–80%) but slightly decreased the hepatic total cholesterol level (12–17%) in normal mice. Co‐administration of bicyclol with cholesterol/bile salt decreased the hepatic triglyceride and total cholesterol levels (7–15% and 25–31%, respectively), when compared with the drug‐untreated and cholesterol/bile salt‐treated group. Bicyclol treatment for 7 days decreased hepatic triglyceride (5–76%) and total cholesterol (5–48%) levels in mice fed with high‐fat/cholesterol diet. In contrast, bicyclol treatment increased the serum triglyceride level (18–77%) in mice treated with cholesterol/bile salt or fed with high‐fat/cholesterol diet. Bicyclol treatment also caused an increase in hepatic index of normal and hypercholesterolaemic mice (3–32%). The results indicate that bicyclol treatment can invariably decrease hepatic lipid levels and increase serum triglyceride levels in normal and hypercholesterolaemic mice.

[1]  S. Pan,et al.  Bifendate treatment attenuates hepatic steatosis in cholesterol/bile salt- and high-fat diet-induced hypercholesterolemia in mice. , 2006, European journal of pharmacology.

[2]  Yi-fan Han,et al.  High doses of bifendate elevate serum and hepatic triglyceride levels in rabbits and mice: animal models of acute hypertriglyceridemia , 2006, Acta Pharmacologica Sinica.

[3]  S. Pan,et al.  A novel experimental model of acute hypertriglyceridemia induced by schisandrin B. , 2006, European journal of pharmacology.

[4]  J. Mckenney,et al.  Safety and efficacy of long-term co-administration of fenofibrate and ezetimibe in patients with mixed hyperlipidemia. , 2006, Journal of the American College of Cardiology.

[5]  Huiping Wang,et al.  Protective effect of bicyclol on acute hepatic failure induced by lipopolysaccharide and D-galactosamine in mice. , 2006, European journal of pharmacology.

[6]  Yuhao Li,et al.  Salacia oblonga root improves postprandial hyperlipidemia and hepatic steatosis in Zucker diabetic fatty rats: activation of PPAR-alpha. , 2006, Toxicology and applied pharmacology.

[7]  G. Farrell,et al.  Nonalcoholic fatty liver disease: From steatosis to cirrhosis , 2006, Hepatology.

[8]  Ye Li,et al.  [Protective effects of bicyclol on alcohol-induced liver damage in mice]. , 2005, Zhonghua yi xue za zhi.

[9]  Shi-yao Chen,et al.  Fatty liver and the metabolic syndrome among Shanghai adults , 2005, Journal of gastroenterology and hepatology.

[10]  A. Benedetti Attraction and growing interest for the fatty liver by the scientific associations. , 2005, European review for medical and pharmacological sciences.

[11]  H. Lo,et al.  Sonographic fatty liver, overweight and ischemic heart disease. , 2005, World journal of gastroenterology.

[12]  Yan Li,et al.  Mechanism of protective action of bicyclol against CCl4‐induced liver injury in mice , 2005, Liver international : official journal of the International Association for the Study of the Liver.

[13]  K. Kondo,et al.  Dietary isohumulones, the bitter components of beer, raise plasma HDL-cholesterol levels and reduce liver cholesterol and triacylglycerol contents similar to PPARalpha activations in C57BL/6 mice. , 2005, The British journal of nutrition.

[14]  H. Tilg,et al.  Treatment strategies in nonalcoholic fatty liver disease , 2005, Nature Clinical Practice Gastroenterology &Hepatology.

[15]  Yan Li,et al.  Toxicity of novel anti-hepatitis drug bicyclol: a preclinical study. , 2005, World journal of gastroenterology.

[16]  Yan Li,et al.  [Protective effects of bicyclol on liver fibrosis induced by carbon tetrachloride]. , 2004, Zhonghua yi xue za zhi.

[17]  Robert K. M. Ko,et al.  Schisandrin B and Other Dibenzocyclooctadiene Lignans , 2004 .

[18]  Geng-tao Liu,et al.  Inhibition of Fas/FasL mRNA expression and TNF-alpha release in concanavalin A-induced liver injury in mice by bicyclol. , 2004, World journal of gastroenterology.

[19]  Shankuan Zhu,et al.  The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988-1994. , 2003, Archives of internal medicine.

[20]  Hong Lu,et al.  Effects of bicyclol on aflatoxin B1 metabolism and hepatotoxicity in rats. , 2002, Acta pharmacologica Sinica.

[21]  Ming-ming Wang,et al.  [Anti-HBV efficacy of bifendate in treatment of chronic hepatitis B, a primary study]. , 2002, Zhonghua yi xue za zhi.

[22]  G. T. Liu,et al.  [Effect of bicyclol on acetaminophen-induced hepatotoxicity: energetic metabolism and mitochondrial injury in acetaminophen-intoxicated mice]. , 2001, Yao xue xue bao = Acta pharmaceutica Sinica.

[23]  G. Liu,et al.  [Protective effect of bicyclol on concanavalin A-induced liver nuclear DNA injury in mice]. , 2001, Zhonghua yi xue za zhi.

[24]  S. Takase,et al.  Effect of fenofibrate on fatty liver in rats treated with alcohol. , 2001, Alcoholism, clinical and experimental research.

[25]  C. Packard Overview of fenofibrate. , 1998, European heart journal.

[26]  S. Eaton,et al.  Multiple biochemical effects in the pathogenesis of alcoholic fatty liver , 1997, European journal of clinical investigation.

[27]  G. T. Liu,et al.  [Effects of 16 drugs on immunological liver injury induced by BCG + lipopolysaccharides in mice]. , 1997, Zhongguo yao li xue bao = Acta pharmacologica Sinica.

[28]  J. Hokanson,et al.  Plasma Triglyceride Level is a Risk Factor for Cardiovascular Disease Independent of High-Density Lipoprotein Cholesterol Level: A Metaanalysis of Population-Based Prospective Studies , 1996, Journal of cardiovascular risk.

[29]  Liu Gt Pharmacological actions and clinical use of fructus schizandrae. , 1989 .

[30]  C. Wu,et al.  RETROCAVAL URETER: REPORT OF A CASE. , 1963, Chinese medical journal.

[31]  Yuhao Li,et al.  Salacia oblonga root improves cardiac lipid metabolism in Zucker diabetic fatty rats: modulation of cardiac PPAR-alpha-mediated transcription of fatty acid metabolic genes. , 2006, Toxicology and applied pharmacology.

[32]  J. Nan,et al.  Protective effects of chalcone derivatives for acute liver injury in mice , 2005, Archives of pharmacal research.

[33]  A. Sanyal Mechanisms of Disease: pathogenesis of nonalcoholic fatty liver disease , 2005, Nature Clinical Practice Gastroenterology &Hepatology.

[34]  Min-li,et al.  Inhibition of Fas/FasL mRNA expression and TNF-a release in concanavalin A-induced liver injury in mice by bicyclol , 2004 .

[35]  Yao Guang A randomized double-blind controlled trial of bicyclol in treatment of chronic hepatitis B , 2002 .

[36]  L. Geng The anti-virus and hepatoprotective effect of bicyclol and its mechanism of action , 2001 .

[37]  A. V. Sechkin,et al.  Developmental and pharmacological regulation of apolipoprotein C-II gene expression. Comparison with apo C-I and apo C-III gene regulation. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[38]  G. T. Liu Pharmacological actions and clinical use of fructus schizandrae. , 1989, Chinese medical journal.