Protective effect of bicyclol on acute hepatic failure induced by lipopolysaccharide and D-galactosamine in mice.
Bicyclol, a new anti-hepatitis drug, has been found to protect against liver injury induced by certain hepatotoxins. The present study was to investigate the effect of bicyclol on acute hepatic failure caused by an intraperitoneal injection of lipopolysaccharide (LPS, 15 microg/kg) and D-galactosamine (800 mg/kg) in mice. Bicyclol (150, 300 mg/kg) was given to mice orally once or three doses before the injection of LPS/D-galactosamine. The liver injury was assessed biochemically and histologically. The mortality in mice was monitored for 48 h after LPS/D-galactosamine poisoning. The expressions of cytokines, adhesion molecules and LPS receptors were determined. As a result, bicyclol showed significant protection as evidenced by the decrease of elevated aminotransferases and total bilirubin, reversion of prolonged prothrombin time and improvement of liver pathological injury in a dose-dependent manner. Pretreatment with bicyclol (300 mg/kg) also lowered the mortality after LPS/GalN intoxication. Furthermore, bicyclol inhibited the elevation of serum tumor necrosis factor-alpha, interferon-gamma and markedly enhanced interleukin-10. The expressions of intercellular adhesion molecule-1, lymphocyte function-associated antigen 1 and the transcription of CD14 and toll-like receptor 4 were also suppressed by bicyclol. These results suggest that bicyclol has remarkable hepatoprotective effects on LPS/D-galactosamine-induced liver injury and the possible mechanism is related to its anti-inflammatory action.
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1, Xian Nong Tan Street, Beiging, 100050 PR China. whp2003@imm.ac.cn
Huiping
H
Wang
Yan
Y
Li
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005688:Galactosamine / Q000633:toxicity; D005786:Gene Expression Regulation; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017114:Liver Failure, Acute / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016169:Lymphocyte Function-Associated Antigen-1; D012333:RNA, Messenger; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D005688:Galactosamine; D007371:Interferon-gamma; C477843:bicyclol