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Studies On Pharmacodynamic Of Jinglingxiaoliu Capsule Long Term Toxicity Study Of Jinglingxiaoliu Capsule On Beagle Dogs

Posted on:2011-05-04Degree:MasterType:Thesis
Country:ChinaCandidate:Y LiuFull Text:PDF
GTID:2144360305467805Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Objective:To investigated the anti-tumor and Immunomodulatory activities of Jinglingxiaoliu Capsule in vitro and in vivo.Method:In vivo:After mice were randomized by body weight, administered intragastrically Jinglingxiaoliu Capsule in low, medium, high doses(100,200, and 300mg-kg-1), control,model,positive drug control groups were set up according to different experiment.Inhibitory action to H22, Lewis, S180 carcinoma experiments, cyclophosphamide synergistic effect experiment and H22 transplantational ascites carcinoma survival rate experiment by vaccinating fluid tumor at the axillary of mice were used to evaluate the effect of Jinglingxiaoliu Capsule on anti-tumor.Swimming load test and closed bottle test by recording swimming time and hypoxia tolerance time were investigated the effect of Jinglingxiaoliu Capsule on anti-defatigation and hypoxia tolerance abilities.Delayed-type hypersensitivity experiment, counting ear swelling degree was used to research the effect of Jinglingxiaoliu Capsule on immunoregulatory.Protective effect on leucopenia induced by cyclophosphamide experiment,the peripheral hemogram,thymus index and spleen index were detected.in vitro:MTT assay was performed to evaluate the effects of Jinglingxiaoliu Capsule on five human clone cancer cell lines.Results:In vivo, The result of inhibitory action to carcinoma experiment treatment with Jinglingxiaoliu Capsule at 300mg/kg group reduced H22 tumor growth by 40.23%(P<0.05 compared with control); Lewis tumor growth inhibition rates treated with Jinglingxiaoliu Capsule at 100mg-kg-1,200mg-kg-1, and300mg-kg-1 were 27.75,34.31,39.52%(P<0.01),respectively,as well as S180 tumor growth inhibition rates treated same dose were 29.36,32.42(P<0.05),49.35%(P<0.01),respectively. The result of cyclophosphamide synergistic effect experiment show Jinglingxiaoliu Capsule in conjunction with cyclophosphamide significantly inhibited the growth of H22, the inhibition rates were 33.76,41.51,50.28%(P<0.01), respectively. H22 transplantational ascites carcinoma survival rate experiment show 300mg/kg group extend mice life span to days 18.6±2.40 (P<0.01).The result of delayed-type hypersensitivity experiment showed 300 mg-kg-1 dose group of Jinglingxiaoliu Capsule significantly reinforce the swelling degree of mice ear to 24.1±9.61(P<0.05 compared with model).The result of anti-defatigation test showed the 300 mg-kg-1 dose group of Jinglingxiaoliu Capsule significantly reinforced the anti-defatigation ability of mice to minutes 30.9±10.75 (P<0.01); The result of hypoxia tolerance test suggested the 300 mg-kg-1 dose group significantly reinforced the hypoxia tolerance ability of mice to minutes 29.2±7.73 (P<0.05).The result of Protective effect on leucopenia induced by cyclophosphamide showed Jinglingxiaoliu Capsule was no significant difference with model group.in vitro:Through the MTT assay could inhibit the growth of cancer cells derived from different tissues, which included human colon cancer cells (HCT-8), human hepatocellular carcinoma cells (Bel-7402), human gastric cancer cells (BGC-823),human lung adenocarcinoma cells (A549), human ovarian cancer cells (A2780). MTT assay showed that the IC50 toward these tumor cells was 80.9-159.5μg/ml.Conclusion:in vivo Jinglingxiaoliu Capsule could inhibit H22,Lewis,S180 tumor growth and increased Immunomodulatory activities.in vitro Jinglingxiaoliu Capsule could inhibit a variety of tissue-derived tumor cells. Objective:To evaluate the long term toxicity of Jinglingxiaoliu Capsule on Beagle Dogs, and to provide safety evidences and dose range for clinical experiment.Method:A total of 18 beagle dogs were equally assigned to receive Jinglingxiaoliu Capsule at low, medium, high doses(0.25,0.60, and 1.50g-kg-1), and 6 (blank control group) to receive placebo, the sex ratio of male to female in each group was 1:1. The beagle dogs were administered intragastrically for 6 consecutive days per week and up to 180 days. All the laboratory indicators were monitored and the recovery of the beagle dogs were observed.RESULTS:During medication, the electrocardiogram(ECG) indicators,0.60g·kg-1 group decreased heart rate,0.60,1.50g-kg-1 groups decreased PR interval and 0.25g-kg-' group decreased QRS interval. The hematological indicators, WBC increased were noted in 1.50g-kg-1 group. The blood biochemical indicators,0.25,1.50g-kg-1 groups decreased TP, 0.60g-kg-1 groups increased BUN, and 0.25, 0.60g-kg-1 groups decreased TG compared with control group after the beagle dogs were administered 90 days.1.50g·kg-1 group decreased ALB after the beagle dogs were administered 180 days. During the recovery stage, all of these changes were reversible. The uric biochemical indicators, the dogs in every group was positive in uric biochemical test during the medication and recovery stages, but no evident difference was found compared with history data. No significant drug-associated toxic reactions were noted from beagle dogs'body weight, temperature, appetite, electrocardiogram(ECG), hematology test, blood biochemical analysis, ophthalmology test, routine urianlisis, histopathologic examination, etc.CONCLUSION:The non-toxic dose of Jinglingxiaoliu Capsule for beagle dogs was 0.60g·kg-1...
Keywords/Search Tags:Jinglingxiaoliu Capsule, Anti-tumor activity, Immunomodulatory activity, beagle dog, Long-term toxicity
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