Bicyclol: a novel antihepatitis drug with hepatic heat shock protein 27/70-inducing activity and cytoprotective effects in mice.
Heat shock proteins (HSPs) are the best-known endogenous factors that protect against cell injury under various pathological conditions and that can be induced by various physical, chemical, and biological stressors. New research seeks to discover a compound that is clinically safe and can induce the accumulation of HSPs in patients. This paper reports that the oral administration of three doses of bicyclol, a novel antihepatitis drug, induced hepatic HSP27 and HSP70 expression in a time- and dose-dependent manner, and that bicyclol treatment stimulated heat shock factor 1 (HSF1) activation in mice. The inducing effects of bicyclol on HSP27, HSP70 and HSF1 were all blocked by quercetin, an inhibitor of HSP biosynthesis. The cytoprotective effect of HSP27/70 induced by bicyclol against hepatotoxicity of acetaminophen (AP) was assessed in mice. The prior administration of bicyclol markedly suppressed AP-induced liver injury as indicated by the reduction in the elevation of serum alanine aminotransferase and aspartate aminotransferase, in liver necrosis, in the release of cytochrome c and apoptosis-inducing factor from mitochondria, as well as in hepatic deoxyribonucleic acid fragmentation in mice. However, all the above actions of bicyclol against AP-induced mouse liver injuries were significantly attenuated by quercetin. This is the first report to show that bicyclol induces hepatic HSP27/70 expression via activation of HSF1 and that the cytoprotective action of bicyclol against liver injury is mediated by its induction of HSP27/70. These results provide new evidence for elucidating the mechanism of the hepatoprotective action of bicyclol in animals and patients.
Bao
Xiu Qi
XQ
Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences, 1 Xian Nong Tan Street, Beijing, China.
Liu
Geng Tao
GT
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001713:Biphenyl Compounds / Q000378:metabolism* / Q000627:therapeutic use; D019610:Cytoprotection; D004268:DNA-Binding Proteins / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006505:Hepatitis / Q000188:drug therapy*; D008099:Liver / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D011794:Quercetin / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D000975:Antioxidants; D001713:Biphenyl Compounds; D004268:DNA-Binding Proteins; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C490017:Hsf1 protein, mouse; C486699:Hspb2 protein, mouse; D014157:Transcription Factors; C477843:bicyclol; D011794:Quercetin