Compare The Different Effects Of Cantharidin And Norcantharidin On Target Organs

ObjectiveTo compare the toxicity of cantharidin with that of norcantharidin in mice,the effect of the two drugs on the blood biochemical index of Balb/c mice was compared with that of the two drugs.To analyze the difference of target organs and the degree of injury in different tissues and organs.MethodsExperiment 1:Compare cantharidin and norcantharidin LDsosThe minimum total lethal dose and the maximum tolerated dose of the two drugs were obtained by pre experiment.According to the results of the pre experiment,the different doses of the two drugs were administered to each of the five groups.Balb/c mice were treated with cantharidin or norcantharidin at different levels for two weeks to determine their LD₅₀s by the profit analysis method.Experiment 2:Compare the toxicity of cantharidin 1/2 LD₅₀ and norcantharidin 1/2 LD₅₀ in miceThe control group,cantharidin 1/2 LD₅₀ dose group and norcantharidin 1/2 LD₅₀ dose group were established,respectively.New cohorts of mice were then treated with 1/2 LD₅₀ of the respective drugs or the vehicle for 2 weeks.During the treatment,the body weight behavior of the mice were monitored.Experiment 3:Compare the serum biochemical indexes in mice treated with cantharidin 1/2 LD₅₀ and norcantharidin 1/2 LD₅₀3 groups of mice,including the normal group,were treated for the end of the 2 week.The serum levels of ALT,AST and BUN were detected by blood sampling in mice,and there were significant differences between the three blood biochemical indexes.Experiment 4:Compare the tissue injury degree of cantharidin 1/2 LD₅₀ and norcantharidin 1/2 LD₅₀ administration groupAt the end of the treatment,tissue samples from the livers,intestines,kidneys and bladders were harvested for histo-pathological analyses.The kidneys were stained with PAS,and the liver was stained with Masson staining.ResultsExperimental results 1:According to the results of pre experiment,the minimum lethal dose of cantharidin was 3.0 mg · kg-1,and the minimum lethal dose of norcantharidin was 30 mg · kg-1.The LD₅₀ of cantharidin was 2.045 mg · kg-1,95%confidence interval（1.8261,2.2639）.The LD₅₀ of norcanditharidin was 20.966 mg · kg-1,95%confidence interval（18.608,24.158）.Experimental results 2:The food intake and body weight of mice were no different from those of the normal group,and the toxic manifestation in the two groups were different.Compared with the normal control group,there was no significant difference in the results of ALT.Experimental results 3:AST and BUN detection in cantharidin group.Norcantharidin,but not cantharidin caused significant elevations of ALT and BUN（P<0.05）.Experimental results 4:Norcantharidin caused inflammatory cell infiltration and vacuolar change in liver,and injuries in the glomeruli and renal tubules.The cantharidin led to the enlargements of intestinal lymph nodes the lobulation in the intestine,the vascular,bladder,and mucosa inflammation in the bladder.ConclusionThe median lethal dose of cantharidin was about 10 times that of norcantharidin.Cantharidin 1/2 LD₅₀ dose group in the blood biochemical index,and in a variety of pathological staining method,showed no damage on liver and kidney,but in pathological experiments of intestinal and bladder showed inflammatory reaction.Norcantharidin on blood biochemical indexes in the dose of 1/2 LD₅₀ showed liver and kidney damage in a variety of pathological staining test in inflammatory reaction and renal tissue of the same clear visible diffuse liver injury of renal tubular and glomerular crescents appear,but no inflammatory stimulus response in the small intestine and bladder pathology.Treatments with equitoxic doses of norcantharidin and cantharidin led to distinct organ/tissue-specific damages in mice.Norcantharidin,but not cartharidin,caused severe damages in the liver and kidney,while cantharidin led to more severe injuries in the intestinal and bladder compared to those inflicted by norcantharidin.