Pharmacodynamic Study Of Suramin Sodium On Liver Fibrosis And Liver Cancer

Suramin is a kind of naphthoquinone sulfonic acid salts, synthetic anionic compounds,used in the treatment of African trypanosomiasis and dish silk worm disease.Then, it is ever tried to the treat HIV/AIDS and malignant tumor.The studies have shown that sodium suramin may have curative effect to liver fibrosis and liver cancer, my company has approved the project of injectable suramin sodium,which is a new drug entity for the treatment of liver cancer and liver fibrosis.In order to to test and verify the efficacy on liver fibrosis and liver cancer, we designed this preliminary pharmaceutical research.This article has successfully established liver fibrosis animal model by injecting CCl4 subcutaneously, respectively giving the active drug Marlowe and different doses of suramin sodium for injection, sacrificing the animals after 24 hours, then separating blood serum,testing ALT, AST, TBIL, HA and PIIINP levels and calculating A/G. Reserving each animal liver tissue to determine liver hydroxyproline, the same parts of the large lobeof the liver tissue is used to pathological examination. Statistically processed by variance analysis and Student-Newmann-Keuls test after fasening method. Giving CCl4 to rats, the liver hydroxyproline and serum ALT, AST, TBIL, HA and liver Hyp content were significantly increased, and A/G decreased dramatically, compared with normal group, it has significant differences,but serum PIIINP levels has no obvious change. The building of the animal model is proved a success. Serum ALT, AST, TBIL, HA and liver Hyp of active control group Marlowe ester are obviously improved, and the reduction in the A/G also has obvious protective effect. The Suramin sodium groups have obviously improved of the liver Hyp caused by increased CCl4. In addition, the medium and high dose groups compared with the model group have a significant reduction in serum ALT, the small andhigh dose groups are significantly lower for the rise of the HA. The animals are died in different degrees during test in each Suramin sodium dose group. Histopathological test results have shown that,compared with normal group, the degeneration and necrosis, the infiltration of inflammatory cells, the hyperplasia in small bile ducts and fibrous connective tissue, andthe formation of pseudolobule is extensively seen in liver cells of model group, indicating the rat liver fibrosis induced by CCl4 subcutaneously a success. Active medicine Marlowe ester of CCl4 induced liver injury and liver fibrosis in rats has obvious protective effect,while suramin is muchweaker than Marlowe ester.This article selected the anthropogenic(7402) liver cancer tumor strains of liver cancer animal models, developed by intraperitoneal injection of suramin and respectively compared with positive drug taxol, observed tumor inhibition rate(%)after injectionand the relative tumor proliferation rate of T/C(%). According to the analysis of experimental data to paclitaxel 5 mg/Kg group of anthropogenic(7402) nude mouse model of liver cancer, it has obvious inhibition, tumor inhibition rate was 72.7%(P < 0.001), the relative tumor increment rate is 45.4%. In low, medium and high dose group of intraperitoneal injection of sodium suramin, the tumor inhibition rate was 3.2%, 5.1%, 5.1%, compared with normal saline group, there is no significant difference. Compared with the simple paclitaxel group, the tumor inhibition rate of suramin sodium combined taxol group was72.1% and did not show obvious tumor suppression effect and synergistic effect of chemotherapy.This study established the liver fibrosis and liver cancer animal model, by choosing active medicine to compare with sodium suramin, and compared the efficacy of different doses of sodium suramin, the results have shown that sodium suramin in the treatment of liver fibrosis has certain protective effect but significantly weaker than Marlowe ester and appears a number of death, which indicates high toxicity. Sodium suramin for liver tumor inhibition rate is low and shows no significant suppression effect and synergistic effect of chemotherapy on anthropogenic(7402) nude mouse model of liver cancer compared with paclitaxel.