Abstract
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.
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Abbreviations
- HSPs:
-
heat shock proteins
- ALT:
-
alanine aminotransferase
- AST:
-
aspartate aminotransferase
- AP:
-
acetaminophen
- PEG-400:
-
polyethylene glycol 400
- RT-PCR:
-
reverse transcription-polymerase chain reaction
- dNTP:
-
deoxy-ribonucleoside triphosphate
- TBE:
-
Tris-borate buffer
- SDS-PAGE:
-
sodium dodecyl sulfate polyacrylamide gel electropheresis
- PVDF:
-
polyvinylidene difluoride
- HSF1:
-
heat shock factor-1
- AIF:
-
apoptosis-inducing factor
- EMSA:
-
electrophoretic mobility shift assay
- HSE:
-
heat shock element
- mRNA:
-
messenger ribonucleic acid
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Acknowledgements
This work was supported by grants from the Chinese Ministry of Science and Technology (96-901-01-45) and from the Chinese Medical Board in New York (93-582).
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Bao, X.Q., Liu, G.T. Bicyclol: a novel antihepatitis drug with hepatic heat shock protein 27/70-inducing activity and cytoprotective effects in mice. Cell Stress and Chaperones 13, 347–355 (2008). https://doi.org/10.1007/s12192-008-0034-4
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DOI: https://doi.org/10.1007/s12192-008-0034-4