Anti-lipid peroxidation and protection of liver mitochondria against injuries by picroside II.
OBJECTIVE
To investigate the anti-lipid peroxidation and protection of liver mitochondria against injuries in mice with liver damage by picroside II.


METHODS
Three animal models of liver damage induced by carbon tetrachloride (CCl(4): 0.1 mL/10 g, ip), D-galactosamine (D-GalN: 500 mg/kg, ip) and acetaminophen (AP: 0.15 g/kg, ip) were respectively treated with various concentrations of picroside II (5, 10, 20 mg/kg, ig). Then we chose the continuously monitoring method (recommended by International Clinical Chemistry League) to analyze serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values, Marland method to detect the activity of manganese-superoxide dismutase (SOD) in liver mitochondria, TBA colorimetry to determine the content of malonicdialdehyde (MDA) in liver tissue, DTNB method to evaluate the activity of glutathioneperoxidase (GSH-Px) and Lowry method to detect protein level in liver tissue. Meanwhile, effects of picroside II on the activity of ATPase and swelling extent of mitochondria in hepatocytes damaged by AP were also evaluated.


RESULTS
Picroside II could significantly prevent liver toxicity in the three models of liver damage. It decreased the high levels of ALT and AST in serum induced by the administration of CCl(4), D-GalN and AP, reduced the cellular damage of liver markedly, and appeared to be even more potent than the positive control drug of biphenyl dimethyl dicarboxylate pilules (DDB). In groups treated with different doses of picroside II, compared to the model group, the content of MDA in serum decreased evidently, whereas the content of SOD and GSH-Px increased in a dose-dependent manner, and the difference was statistically significant. Further, in the study of AP model, picroside II inhibited AP-induced liver toxicity in mice, enhanced the activity of ATPase, improved the swelling extent of mitochondria and helped to maintain a normal balance of energy metabolism.


CONCLUSIONS
Picroside II can evidently relieve hepatocyte injuries induced by CCl(4), D-GalN and AP, help scavenge free radicals, protect normal constructions of mitochondria membrane and enhance the activity of ATPase in mitochondria, thereby modulating the balance of liver energy metabolism, which might be part of the mechanisms of hepatoprotective effects of picroside II.
Gao
Hua
H
Department of Chemistry, College of Chemistry and Molecular Engineering, Beijing University, Beijing 100871, China.
Zhou
Ya-Wei
YW
D000818:Animals; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism*; D002934:Cinnamates / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005960:Glucosides / Q000494:pharmacology*; D057888:Iridoid Glucosides; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects
D002934:Cinnamates; D005960:Glucosides; D057888:Iridoid Glucosides; C416837:picroside II; D002251:Carbon Tetrachloride