bicyclol and Fatty-Liver

Four hospitals in China.. To evaluate the clinical efficacy and safety of using bicyclol in conjunction with glucurolactone in preventing drug-induced liver injury (DILI) in tuberculosis (TB) patients suffering from underlying liver disease.. A total of 240 initially treated TB patients who were healthy hepatitis B carriers or had pure steatosis were randomised into two equal groups; both received an oral glucurolactone tablet 600 mg/day (200 mg three times daily) as basic liver protection. The test group also received 75 mg/day (25 mg three times daily) bicyclol tablets orally, while the control group received no other liver protection. The incidence of liver injury in the two groups, the adjustment or termination of anti-tuberculosis chemotherapy and any adverse reactions were assessed.. The incidence rate and level of severity of liver injury and the termination rate of anti-tuberculosis treatment in the test group were lower than that of the control group (P < 0.05). The overall time of occurrence of liver injury was significantly different between the two groups (P < 0.05).. Adding bicyclol to basic liver protectants may effectively and safely prevent the occurrence of anti-tuberculosis DILI in patients with underlying liver disease, and help simplify anti-tuberculosis treatment.

Topics: Adolescent; Adult; Aged; Antitubercular Agents; Biphenyl Compounds; Chemical and Drug Induced Liver Injury; China; Fatty Liver; Female; Hepatitis B; Humans; Liver; Male; Middle Aged; Risk Factors; Treatment Outcome; Tuberculosis; Young Adult

Topics: Adult; Biphenyl Compounds; Fatty Liver; Female; Humans; Hypolipidemic Agents; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Phosphatidylcholines; Young Adult

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.

Topics: Acyl-CoA Dehydrogenase, Long-Chain; Acyl-CoA Oxidase; Administration, Oral; Alanine Transaminase; Animals; Aspartate Aminotransferases; Biphenyl Compounds; Cytochrome P-450 CYP2E1; Cytochrome P-450 CYP4A; Disease Models, Animal; Electron Transport Complex I; Electron Transport Complex IV; Fatty Acids; Fatty Liver; Lipid Peroxidation; Liver; Male; Mice; Mice, Inbred ICR; Mitochondria, Liver; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Oxidative Stress; PPAR alpha; Protective Agents; Tetracycline; Time Factors

To study the effect of bicyclol on lipid disorder and liver damage induced by tetracycline in mice, mice were given (ig) bicyclol (75, 150, and 300 mg x kg(-1)) three times before or after administration of tetracycline (180 mg x kg(-1)). The contents of hepatic lipids, MDA and GSH, serum lipids and ALT/AST levels were measured 24 hours after the injection (ip) of tetracycline. The beta-oxidation rate of hepatic mitochondrial fatty acid and hepatic secretion of VLDL were also observed. Bicyclol (150 and 300 mg x kg(-1)) provided significant protection against fatty liver by inhibiting the elevation of hepatic TG and CHO, adjusting abnormal serum lipids, inhibiting the elevation of serum ALT, AST, and ameliorating the severity of pathological changes. Furthermore, bicyclol significantly accelerated the VLDL (TG) secretion and reversed the impairment of mitochondrial oxidation, resulting in the lipid homeostasis. The increase of MDA formation and depletion of GSH that reflect lipid peroxidation induced by tetracycline were also inhibited by bicyclol administration. The results indicated that the hepatoprotection of bicyclol was mostly due to the improvement on lipid oxidation and transportation as well as the inhibition of lipid peroxidation in tetracycline-intoxicated mice.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Biphenyl Compounds; Cholesterol; Cholesterol, VLDL; Fatty Acids; Fatty Liver; Glutathione; Lipid Peroxidation; Liver; Male; Malondialdehyde; Mice; Mice, Inbred ICR; Mitochondria, Liver; Protective Agents; Random Allocation; Tetracycline; Triglycerides