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

Toxicology. 2009 May 6; Yu HY, Wang BL, Zhao J, Yao XM, Gu Y, Li YPeroxisome 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, 300mg/kg) was given orally three times in two consecutive days. Tetracycline (200mg/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) complex I&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.