Studies On Toxicity And Antitumor Activity Of Buthus Martensii Karsch Powder

Objective: To investigate the toxicity dosage,toxicity,possible toxicity target organs,and explore the preliminary research on antitumor activity in vitro and in vivo of Buthus martensii Karsch powder.Methods:?1?Acute toxicity test: Preparing 6 concentration of Buthus martensii Karch powder?700 times,625 times,559 times,500 times,447.5 times,400 times equivalent the clinical dose?mixed suspension,six groups of Kunming mice were given drug by intragastric administration once,to observe 14d's acute toxicity and death situatiation,and calculate the half lethal dose(LD₅₀).?2?Long-term toxicity test: Buthus martensii Karch powder of different doses?40 times,20 times,10 times as clinical commonly used dose?and normal saline used to four groups of SD rats for 10 weeks and recovered for 4 weeks,to observe rats' general behavior,the changes of the physiological indexes,determination of blood index,blood biochemistry,organ weight and organ coefficient.To investigate the possible toxic target organs,and to exam the pathological organs and tissues.?3?Antitumor activity in vivo and in vitro: The effect of Buthus martensii Karch powder on the proliferation of tumor cells,such as human erytholeukemia cell line K562,human lung carcinoma cell line A549,human hepatocellular carcinoma cell line SMMC-7721,human colon carcinoma cell line HCT116 and human gastric cancer cell line BGC-823,was detected by CCK-8 assay.The inhibition of Buthus martensii Karch powder on tumor growth in mice was observed by the sarcoma S180 and liver cancer H22 transplanted tumor model.Results:?1?Acute toxicity test: After the intragastric administration of six concentration of Buthus martensii Karch powder,most of the mice showed behaviour change,short excited,difficulty in breathing,death?no sex difference?,also appeared tonic spasm,convulsions vulsions,incontinence of urine.The 100% lethal dose rate is equal to 14 g / kg and 0% death rate of dose is equal to 8g/kg;the value of LD₅₀ is 10.1999 g/kg,95% confidenceinterval is between 9.8243 g / kg and 10.5898 g / kg.?2?The long-term toxicity test: Buthus martensii Karch powder has little effect on the body weight growth of rats,and that effects female rats more significantly than male rats.In medium and high dose groups,male visible animals loose stools and administration in the 7th week starting,in high dose group,some male rats spirited slightly sluggish,with relatively darker hair color,but they recovered growly in convalescence.Medicine for 4 weeks,in the high dose group,the value of AST was higher than the negative control group;in the middle dose group,the value of TG and Na was lower than the negative control group;in the low dose group,there was 1 case of mild inflammation of the lungs.Medicine for 10 weeks,in medium and low dose,the value of TP group is higher than that of the negative control group;in high dose group,the value of AST is higher than the negative control group;in the high,middle and low dose groups,the value of CK is lower than that in negative control group;in low dose group,the value of BUN is higher than that of the negative control group;in low dose group,the value of of Glu is lower than that of negative control group;in low dose group,the value of Na is higher than that of negative control group.Pathological examination results are as follows:?Lung pathological changes: 2 cases of mild inflammation in low dose group,1 case of mild inflammation in middle dose group,1 case with mild fibrosis,2 cases with high dose of mild inflammation.?Liver lesions: 2 cases of mild edema in high,medium and low dose group.?Renal pathological changes: 1 case of mild fibrosis in high dose group.?Testicular lesions: 1 case of testicular necrosis in high dose group.In withdrawal period,in high dose group,the levels of ALT and AST are higher than that of the negative control group,in low dose group,the level CK is lower than that of negative control group,TG is higher than that of the negative control group,kidney coefficient is lower than that in the negative control group,in low dose group of,brain wet weight is higher than the negative control group.Pathological examination results are as follows: ?Lung pathological changes: 1 case of mild inflammation and 1 case of mild fibrosis in middle dose group,1 case of mild inflammation and 1 case of severe fibrosis in high dose group.? The renal lesions: 1 case of mild fibrosis.?3?Antitumor activity in vivo and in vitro: Buthus martensii Karch powder inhibited many tumor cell proliferation,and exhibited stronger antitumor activity on K562 cell lines.Buthus martensii Karch powder showed strong inhibition on the growth of sarcoma S180 and liver cancer H22 in mice,at dosage of 1.28 g/kg,inhibitory rate was 45.81 and 53.04% respectively.Conclusion:?1?The acute toxicity reaction of Buthus martensii Karch powder major injured nervous system and respiratory system.LD₅₀ value was 10.1999 g /Kg,Buthus martensii Karch powder belonged to slightly toxic drug.?2?The longterm toxicity of Buthus martensii Karch powder mainly mainly has damage to the liver,lung,kidney,may also have slight damage to testis.?3?Buthus martensii Karch powder exhibited certain antitumor activity in vivo and in vitro,but it needs to be waited for follow-up researchers such as separation,extraction,purification to further study.