Pharmacokinetics And Pharmacodynamic Of Realgar Bioleaching Solution

RBS has been showed a obvious anti cancer activity in hepatocellular both in vivo and vitro.In order to further test the anti cancer activity of RBS,this study is focus on pharmacokinetics and pharmacodynamic of RBS.The concentration of RBS in mice blood and tissues have been tested by hydride generation-atomic fluorescence spectrometry(HG-AFS).Valid cells for the further study was screened by MTT examination.Cell cycles and apoptotic cells have been tested by FCM..Moreover,the mRNA level of cyclinA2,survivin,bcl-2 and bax have been determined by realtime PCR.In vivo experiment,oral administration was using to contrast the metabolic parameters in RBS and ATO in Kunming mice.,The Cmax in RBS is 6.5ng/ml and 1.2ng/ml in ATO alternatively.The result shows that RBS has a higher bioavailability than ATO,and have a long-lasting pharmavodynamics in RBS treatment..However,the arsenic amount of RBS treated in tissues are higher than ATO group.It probably means that RBS may has an equal effect to ATO ata lower dosage,In MTTexperiment,,we found that RBS was more sensitive on leukemia cell lines than normal cell lines including Hacat and HSEC.The inhibition ratios of RBS treated Raji,K562,K562/ADM and HL-60 are 81.60%?59.09%?26.92%and35.04%respectively in 48h.,but the inhibition ratios of RBS treated Hecat and HSEC are 3.99%and 1.43%.Then,we chose HL-60 cells to do the further research.By MTT assay showed that IC50 of HL-60 cells in RBS treatment were 3.12?g/ml,1.27?g/ml and 0.13?g/ml after 24h,48h and 72h..Cell cycles were significantly inhibited by RBS in G2/M by FCM analysis,and by a dose-dependent manner.Realtime PCR.revealed the mRNA level of cyclinA2,survivin and bcl-2 were decreased and bax was increased in RBS treatment.In conclusion,our results suggest that RBS has a longer half life in tissues,and the bioavailability of RBS is significantly higher than ATO in the same dosage in leukemia cell lines.Moreover,RBS can strongly inducing cell cycle arrest and cell apoptosis in HL-60 cell line in vitro.