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Toxicology. 2009 Jul 10;261(3):112-8. doi: 10.1016/j.tox.2009.04.058. Epub 2009 May 7.

Protective effect of bicyclol on tetracycline-induced fatty liver in mice.

Author information

1
Department of New Drug Development, Institute of Materia Medica, Peking Union Medical College, [corrected] Chinese Academy of Medical Sciences, No. 1, Xian Nong Tan Street, Beijing 100050, PR China.

Erratum in

  • Toxicology. 2010 Jun 29;273(1-3):60.

Abstract

Peroxisome proliferators-activated receptor alpha (PPARalpha) and oxidative stress are two important pathological factors in non-alcoholic fatty liver disease (NAFLD). Tetracycline-induced fatty liver was partly due to the disturbance of mitochondrial fatty acids beta-oxidation regulated by PPARalpha. Bicyclol was found to protect against high fat diet-induced fatty liver through modulating PPARalpha and clearing reactive oxygen species (ROS). The present study was performed to further investigate the effect of bicyclol on tetracycline-induced fatty liver and related mechanism in mice. Bicyclol (75, 150, 300 mg/kg) was given orally three times in two consecutive days. Tetracycline (200 mg/kg) was injected intraperitoneally 1h after the last administration of bicyclol. Oxidative stress, mitochondrial function, PPARalpha and its target genes were evaluated by biochemical and RT-PCR analysis. The activity of CYP4A was assessed by liquid chromatography/mass spectrometry (LC/MS) method. Bicyclol significantly protected against tetracycline-induced fatty liver by reducing the accumulation of hepatic lipids and elevation of serum aminotransferase. In addition, bicyclol remarkably alleviated the over-production of thiobarbituric acid-reactive substance. The reduced activity of mitochondrial respiratory chain (MRC) complexes I and IV and mitochondrial permeability transition (MPT) were also improved by bicyclol. Furthermore, bicyclol inhibited the decrease of PPARalpha expression and its target genes, including long-chain acyl CoA dehydrogenase (LCAD), acetyl CoA oxidase (AOX) and CYP4A at mRNA and enzyme activity level. Bicyclol protected against tetracycline-induced fatty liver mainly through modulating the disturbance of PPARalpha pathway and ameliorating mitochondrial function.

PMID:
19427351
DOI:
10.1016/j.tox.2009.04.058
[Indexed for MEDLINE]

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