Document Detail


Protective effect of bicyclol on tetracycline-induced fatty liver in mice.
MedLine Citation:
PMID:  19427351     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Hong-Yan Yu; Bao-Lian Wang; Jing Zhao; Xiao-Min Yao; Yu Gu; Yan Li
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-07
Journal Detail:
Title:  Toxicology     Volume:  261     ISSN:  1879-3185     ISO Abbreviation:  Toxicology     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-22     Completed Date:  2009-07-09     Revised Date:  2010-06-04    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  112-8     Citation Subset:  IM    
Affiliation:
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.
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MeSH Terms
Descriptor/Qualifier:
Acyl-CoA Dehydrogenase, Long-Chain / metabolism
Acyl-CoA Oxidase / metabolism
Administration, Oral
Alanine Transaminase / blood
Alkane 1-Monooxygenase / metabolism
Animals
Aspartate Aminotransferases / blood
Biphenyl Compounds / administration & dosage,  pharmacology*
Cytochrome P-450 CYP2E1 / metabolism
Disease Models, Animal
Electron Transport Complex I / metabolism
Electron Transport Complex IV / metabolism
Fatty Acids / metabolism
Fatty Liver / chemically induced,  metabolism,  prevention & control*
Lipid Peroxidation / drug effects
Liver / drug effects*,  metabolism
Male
Mice
Mice, Inbred ICR
Mitochondria, Liver / drug effects*,  enzymology,  metabolism
Mitochondrial Membrane Transport Proteins / drug effects,  metabolism
Oxidative Stress / drug effects
PPAR alpha / antagonists & inhibitors,  metabolism
Protective Agents / administration & dosage,  pharmacology*
Tetracycline
Time Factors
Chemical
Reg. No./Substance:
0/Biphenyl Compounds; 0/Fatty Acids; 0/Mitochondrial Membrane Transport Proteins; 0/PPAR alpha; 0/Protective Agents; 0/bicyclol; 0/mitochondrial permeability transition pore; 60-54-8/Tetracycline; EC 1.14.14.1/Cytochrome P-450 CYP2E1; EC 1.14.15.3/Alkane 1-Monooxygenase; EC 1.3.3.6/Acyl-CoA Oxidase; EC 1.3.99.13/Acyl-CoA Dehydrogenase, Long-Chain; EC 1.6.5.3/Electron Transport Complex I; EC 1.9.3.1/Electron Transport Complex IV; EC 2.6.1.1/Aspartate Aminotransferases; EC 2.6.1.2/Alanine Transaminase
Comments/Corrections
Erratum In:
Toxicology. 2010 Jun 29;273(1-3):60

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