[Effect of bicyclol on acetaminophen-induced hepatotoxicity: energetic metabolism and mitochondrial injury in acetaminophen-intoxicated mice].
OBJECTIVE
To investigate the mechanism of the protective effect of bicyclol on acetaminophen-induced hepatotoxicity in mice.


METHODS
31P-MRS spectra in vivo were determined by using surface coil technique. The membrane fluidity of mitochondria and the activity of mitochondrial ATPase were also determined by spectrofluorophogometry and spectrophotometry methods.


RESULTS
The hepatotoxicity of acetaminophen is related to the lipid peroxidation and covalent binding to macromolecules, which leads to damage of mitochondrial function. Our results showed that the decrease of ATP/Pi and the elevation of PME/ATP in acetaminophen-intoxicated mice were significantly inhibited by two doses of bicyclol (100, 200 mg.kg-1) pretreatment, which indicate that bicyclol has significant protective effect on the decrease of liver ATP content induced by acetaminophen. Acetaminophen significantly inhibited the activity of mitochondrial ATPase by its cytotoxic metabolite NAPQI [N-acetyl-p-benzoquinone], which has the potential to react with sulfhydryl groups or through sulfhydryl group oxidation. Our results showed that the reduction of mitochondrial fluidity as well as the inhibitory effect of mitochondrial ATPase induced by acetaminophen were also reduced by bicyclol.


CONCLUSIONS
The effect of bicyclol on acetaminophen-induced liver injury maybe partly due to its protective effects on hepatic energy metabolism and mitochondria function.
Li
Y
Y
Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China. liyan@imm.ac.cn
Dai
G W
GW
Li
Y
Y
Liu
G T
GT
D000082:Acetaminophen / Q000633:toxicity*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000209:etiology*; D004734:Energy Metabolism / Q000187:drug effects*; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects*; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation
D001713:Biphenyl Compounds; D000082:Acetaminophen; C477843:bicyclol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000251:Adenosine Triphosphatases