Pharmacodynamics Study On The Anti - Tumor And Analgesic Effect Of Toad Venom Lipid Microspheres Injection

Chan’su.a traditional Chinese medicine,was prepared from the toad venom of Bufo bufo gargarizens cantor B.melanostictus Schneider or B.raddei strauch.It has been reported that Chan’su has many pharmacological actions,such as anti-tumor,stimulate myocardial contraction and pain relief,et al.The principal biologically activity components of Chan’su are bufadienolides.Bufadienolides lipid microsphere（BU-LM）is a new strategy for drug delivery system of bufadienolides,which contain bufalin,cinobufagin and resibufogenin,mainly.The present study was aimed to investigate the anti-tumor and analgesia effects of BU-LM.Firstly,the acute toxicity,of BU-LM was investigated.The LD₅₀of intravenous injection BU-LM in mice is 13.37 mg/kg and the LD₅₀of intraperitoneal injection is 82.01 mg/kg.We found the principal toxicity of BU-LM was cardiac toxicity.Further more,three kinds of murine tumor models,sarcoma 180（S180）,hepatoma 22（H22）and Lewis lung were employed to observe the anti-tumor effects of BU-LM in vivo.The results showed that BU-LM（0.20,0.40 and 0.80 mg/kg,i.p.）significantly inhibited the growth of the three kinds of tumors,and had no influence on spleens and thymus of mice.To investigate the potential effects of BU-LM combined with CTX in efficacy enhancing and toxicity reducing on sarcoma S180 and H22 hepatic carcinoma in mice.The results showed that the tumor inhibitory rates of the combination group were higher than single treatment group.In addition,the effect of BU-LM on DNA damage induced by CTX in mice peripheral blood cells was observed through the single cell gel electrophoresis.The results show that BU-LM at the dose of 0.40 mg/kg could markly reduce the DNA damage induced by CTX.All the results suggested that combined administration of BU-LM with CTX could display the effects of efficacy enhancing and toxicity reducing.The model of acetic acid-induced writhing,hot-plat test and the chronic constriction injury of the sciatic nerve（CCI）in mice were used to investigate the analgesia effects of BU-LM.The writhing test results showed that BU-LM（0.20 mg/kg -3.20 mg/kg,i.p.）could dose-dependently inhibit the writhing counts induced by acetic acid and the ED₅₀of BU-LM was 0.50 mg/kg. Additionally,the hot-plat test results showed that BU-LM（0.20,0.40,0.80 mg/kg,i.p.）could significantly increase the pain threshold in mice.In present study,a murine model of neuropathic pain,the chronic constriction injury of the sciatic nerve mouse model（CCI）,was estabilished successfully.The CCI mice showed spontaneous pain and inducitivity pain,and the results showed the good consistency.It suggested that the CCI model was builded successfully. BU-LM（0.20,0.40 and 0.80 mg/kg,i.p.,for 7d）displayed significantly analgesic effect on spontaneous pain and inducitivity pain in CCI mice.In summary,all the results in the present study suggested that BU-LM could be used as a potential new drug for anti-tumor and inhibiting cancer pain.