Study on the long-term toxicity of Taizi Shenyue Capsule in rats after 180 days of administration
Objective To investigate the reactions and properties of long-term toxicity of Taizi Shenyue Capsule on rats after 180 days of intragastric administration.Methods A total of 88 Wistar rats(half male and half female),were randomly divided into four experimental groups,including negative(solvent)contrl group and low,medium and high dose of Taizi Shenyue Capsule,with 22 rats in every group(half male and half female),and were administered 0.400g/kg,0.828g/kg and 1.714g/kg of Taizi Shenyue Capsule by oral gavage(equivalent to 23,48 and 100 times of clinical dose,respectively)for a total of 180 days(26 weeks,6 months).After discontinuation,it was reversibly observed for 14 days(2 weeks).On the 180th day,the abdominal aorta blood of rats in the each experimental group was collected to measure blood routine,blood coagulation time and biochemical indexes,and 12 rats were sacrificed in each group after the administration to accept,autopsy and histological examination,and the other 10 rats were observed for reversibility.Heart,liver,spleen,lungs,kidneys,thymus,prostate,testes,epididymis,ovaries,uterus,brain were weighed and organ coefficients were calculated.Histological examination of heart,liver,spleen,lungs,kidneys,brain,adrenal glands,thyroid,thymus,prostate,testes,epididymis,ovaries,uterus,stomach,duodenum,pancreas,aorta and soon were done.After the recovery period(day 196),the corresponding treatment and testing were carried out.Results At the second week of admistration,compared with the control group,the weight growth of male rats in the highdose group decreased significantly(P<0.05),and continued until the end of administration,and the food intake also decreased significantly(P<0.05).The results of blood biochemistry showed that 180 days after administration,the urea(UREA)and creatinine(CRE)levels in the high and medium dose group were lower than those in the control group(P<0.05),but they were within the normal range and had no pathological significance.The alanine aminotransferase(ALT)levels in the convalescent high and mediumdose group were lower than those in the control group(P<0.05),but they were all within the normal range and had no pathological significance.There were no significant changes in other blood routine indexes,blood biochemistry and organ coefficients.There were no pathological morphological changes caused by drug poisoning in each dose group.No delayed toxicity reactions caused by drug were observed two weeks after drug discontinuance.Conclusion The results of this long-term toxicity test show that the drug of 1.714g/kg(equivalent to 100 times of clinical dose)has certain non-specific toxicity reactions,which is a relatively safe dose range,0.400g/kg(equivalent to 23 times of clinical dose)is the absolute safe dose range.
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