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Dioscorea Bulbifera L Sends The Liver Toxicity/To Blend The Angelica Sinensis To Reduce The Poisonous Subcellular Fraction Mechanism And The Toxic Ingredient In Vitro Metabolism Research

Posted on:2010-07-01Degree:DoctorType:Dissertation
Country:ChinaCandidate:J Z WangFull Text:PDF
GTID:1114360275487761Subject:Pharmacy
Abstract/Summary:PDF Full Text Request
objective:In recent years Dioscorea bulbifera L.has been widely used for thetreatment of goiter and various cancers,particularly for the treatment ofcancers.However,in clinical application it is discovered Dioscoreabulbifera L.has a certain toxic reaction,which can cause damage of liverand kidney.The extent of damage is relevant to the doses and time.Thedamage of liver can be demonstrated in a short period while the damage ofkidneys appears after a long time.In the literature it is reported there are 50cases of drug induced hepatitis(3 persons died) for the use of Dioscoreabulbifera L.But it shows that the combination of Dioscorea bulbifera L andangelica could reduce the damage to liver cells more significantly than bysimply using.Dioscorea bulbifera L.can also release the damage to thekidney.When Dioscorea bulbifera L and angelica are combined,the degreeof liver-cell damage will be significantly reduced and to some extentefficacy could be enhanced,which the mechanism is not clear.So the studyof the mechanism is even more critical,not only for reducing the degree ofdrug-induced liver-injury in long-term use and making the adverse reactionsmore clear,but also for security agents in clinical.method:Based on the foundation of Pharmacology experimental reach,thisgroup carries on the discussion on the mechanism,facing the liver toxicityof Dioscorea bulbifera L.and reducing the poisonous while blends theangelica,from the subcellular layer,(by using shines through the electronicmicroscope,the laser altogether to focus and scanning microscope) andstudy the influence to cytochrome P450 mixing function oxydases hypo type1A2,2El,the 3A after blending the angelica and Dioscorea bulbifera L.Themetabolism situation in the liver microsome of its toxic ingredient-Diosbulbin-B,obtained by separation-purification the element through theway of extraction-separation-drug-efficacy-tracing,conducts the research.results: 1.On the foundation of early period research and the further research ofthe blood-serum-zymology-mechanism of Dioscorea bulbifera L.to causethe liver toxic and the cytomorphology,it is certain that the poisonousmechanism is related to oxidized stress concerns.2.Taking withdraws,separation and drug-efficacy tracing as the guidingprinciple,the separation-preparation of the liver toxic ingredient ofDioscorea bulbifera L.is carried on.Unifying the modern spectrummethods like 1H,13C NMR,MS-ESI and so on to carry on the structureappraisal,it is determined that the obtained ingredient is two tie lactoneclass ingredient:Diosbulbin-B.3.The line plastochondria membrane potential and the Ca2+ density inthe cell:Observing the change of plastochondria membrane electricitydislocation and the content of the Ca2+ in the male SD rats liver-cell causedby Dioscorea bulbifera L.and after blends the angelica,the mechanism ofthe poison and the reducing poisonous after blended of Dioscorea bulbiferaL.could be explained from the subcellular stratification plane.4.The exsomatize liver fills:to observe the poisonous function ofDioscorea bulbifera L.and after blend the angelica to the exsomatize liver.Analysis the results both joining the medicine into the perfusate directly tocarry on the circulation and in the body experimental,the toxigenicityfunction of the toxic ingredient of Dioscorea bulbifera L.is caused mainlythrough the mixing function oxydases metabolism in the liver cell,but notthrough metabolism of colony bacteria and intestines cells.After blendingthe angelica the liver toxicity has certain improvement explains thatangelica also has function of the oxidation resistance and the liver damageprotection besides the P-glycoprotein mechanism5.Analyzes the influence of Dioscorea bulbifera L.and blends theangelica to CYP450 enzyme hypo type in the liver of the male clean SD rats,discussing the enzyme reaction to liver medicine ofDioscorea bulbifera L.and after blends. 6.Preparing liver microsome,carrying on the vitro metabolism researchof Diosbulbin-B,fosters 60 minutes,altogether four metabolism-ingredientare produced,respectively be peak 1,2,3,4,which can provide the theorybasis for medicine kinematics research in the body.Conclusion:1.Dioscorea bulbifera L-induced liver toxicity,mainly throughgeneration of oxygen free radicals damage the mitochondria,resulting incellular energy metabolism,mitochondria-dependent cytoplasmic activatedapoptosis pathway,causing cell apoptosis2.To clarify the in vitro metabolism in Dioscorea bulbifera B livermicrosomes in the metabolism for Dioscorea bulbifera B pharmacokineticsof the drug lay the foundation for research.
Keywords/Search Tags:hepatotoxicity, Dioscorea bulbifera L, compatibility, LSCM
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