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Aim of study:Evodiaefructus (EF) has been used in China for thousands of years as an analgesic,antiemetic,anti-inflammatory and antidiarrheal drug.Although recent chronic toxicity studies performed on aqueous extract of EF has revealed that it can produce obvious cumulative hepatotoxicity,but the toxic mechanisms is still uncertain.In the present study,we investigated the influence of EF on oxidative stress,mitochondrial permeability transition,adenosine triphosphate (ATP),and cytochrome C (CytC) releasing of hepatic mitochondrial.Material and methods:Rats were divided int0 4 groups and fed distilled water,6,12,24 g/kg of aqueous extract of EF daily for 15 days.Evodiamine,rutaecarpine and evodine were quantified in aqueous extract by high performance liquid chromatography with ultraviolet detector (HPLC/UV).manganese superoxide dismutase (MnSOD) activity,glutathione (GSH),malondialdehyde (MDA) and ATP contents were determined with commercial Kits.Mitochondria morphology was observed by transmission electron microscopy.The electrical transmembrane potential of mitochondria and concentration of CytC in the endochylema was determined with a commercial ELISA kit.Results:The results showed that aqueous extract of EF could decrease the activities of MnSOD and GSH,increase the content of MDA,induce mitochondria swelling,vacuolation,mitochondrial permeability transition (MPT) pore opening and mitochondrial potential decreasing,resulting in ATP depletion and CytC releasing.Conclusions:In summary,our data suggest that aqueous extract of EF can induce oxidative damage and MPT in rat mitochondria,result in ATP depletion and CytC releasing,triggering cell death signaling pathways,which are partial hepatotoxicity mechanisms of EF.