Toxicoloizical Evaluation Of Two CFTR Inhibitors

This experiment with SPF rats and mice and salmonella typhimurium for testobjects, Toxicological assessment test of CFTR inhibitors toxicity test,mouse spermmutagenicity test, micronucleus test and Salmonella typhimurium mutagenicitytest.In these tests, there have five treatment groups: positive control group(cyclophosphamide40mg/kg), high dose group, the dosage group, low dosegroup.Remove the bone marrow and sperm, statistics through the microscope afterdyeing.the number of spontaneous reverse mutation of strains can judge drugtoxicology security. The results are as follows:(1) measure half lethal dose of Pyrimidine thione and Thiazolidone by the way of upand down result: Pyrimidine thione LD50﹥2000mg/kg Thiazolidone, LD50﹥2000mg/kg. the two drugs are non-toxic substance according to the acute toxicityclassification standard.(2) In micronucleus tests, there were no statistically significant among the eachgroup ratios of PCEs and red bloods cells. As for the ratio of the MPCEs in PCEs,there have statistically significance between positive control groups and samplegroups(SC), sample groups(CSO) both male and female, but there were nostatistically significance between the negative control groups (SC and CSO) andsample groups (SC and CSO). The results show that there is no cell toxicity insample groups, so the two drugs will not have inherent toxicity in mice.(3) In sperm malformation test, the incidence of sperm deformity in sample group isno significant difference (p﹥0.05) compared with that in negative control group.But there have significant difference (p <0.05)cyclophosphamide positive andnegative control groups. These results also show that the two drugs will not haveinherent toxicity in mice.(4) In Salmonella typhimurium mutation assay, the number of spontaneous reversemutation of all negative and positive strains are as expected, the number of positivecontrol strains are at least two times more than negative strains. There is no difference between the number of reverse mutation strains of two drugs being testedand that of the negative control. The ratio of the mean of strains of sample drugs andthat of negative control was between0.5and2.This result suggest the growth ofstrains is not been inhibited and the drugs have no induce to the tested strains.Therefore, the two testing drugs have no strainsmutagenic and action inductivity tothe tested strains.Conclusion: Thiazolidone and Pyrimidine thione in the experiment, won’t causeacute systemic toxicity reaction and without the mutagenic action and hereditarytoxicity, therefore, it has high biosafety. the development and application of Ionchannel blockers about prevention and control PED is in a initial stage, the similarsafety reports has not been seen, so this study of ion blockers provide a reliablesafety data for its development and application in the field of diarrhea.