Developmental Toxicology Of LW1705 On Young Rats Of Different Ages

Objective:In recent years,the pediatric application of traditional Chinese medicine has become a hot topic for researchers.Many kinds of traditional Chinese medicine have been proved by modern tests to have toxicological effects on children.The special characteristics of children determines that special attention should be paid to their safety research.LW1705 is a traditional Chinese medicine syrup.The main ingredient is biliary extract.It has the functions of clearing away heat and detoxifying,reducing swelling and relieving pain,and is used for acute tonsillitis,acute pharyngitis,acute conjunctivitis and upper respiratory tract infection.In this paper,young rats were used as research objects to study the developmental toxicological effects of LW1705 on young rats of different ages.The safety of LW1705 in pediatric drugs was evaluated,and the basic reference data for clinical use of pediatrics was provided.Methods:In this study,young SD rats were selected as experimental objects.According to the comparison of the systematic development process of human and rat organs,three stages were designed according to age groups,i.e.young SD rats with PND4,PND15 and PND40 were gavaged with paediatric drug LW1705 for 18 days,31 days and 66 days respectively.The clinical observation,body weight and food intake,physiological development,nerve reflex,spontaneous behavior,clinical examination and pathological examination were carried out.Toxic reaction results were obtained through data statistics.Results:The results of physical signs observation showd that the young rats in LW1705 high-dose group in the first and second stages had gastrointestinal reactions such as loose stools during the administration period,and no abnormality was found in the recovery period.No abnormality was found in the third stage of clinical observation.The results of various developmental indexes show that the weight,food intake,physiological development index,nerve reflex function index,spontaneous behavior examination index and physical development index of young rats in the first,second and third stages have no effect related to LW1705.The results of physical signs test showed that ALT,AST,TG and LDH levels in LW1705 medium and high dose groups decreased in each stage of administration and recovery.GLU level significantly increased,with a certain dose relationship.In the second and third stages of administration,the pH value of urine increased at each dose and recovered after drug withdrawal.Hematology,immunoglobulin,sex hormone,growth hormone,hepatic microsomal enzyme and bone mineral density have no effect related to LW1705.Signs and pathological examination indexes showd that the weight and coefficient of spleen increased at medium and high doses in the first stage and recovered at recovery stage.There was no drug-related effect on organ weight and coefficient in other stages.In the first stage,each administration group can see that the area and quantity of splenic nodules in spleen are increased to different degrees,with a certain dose correlation,and they completely recovered 15 days after drug withdrawal recovery.No changes related to LW1705 were found in the second and third stages of organ examination.Conclusions:LW1705 is administered when the digestive system of young rats in the first and second stages is not fully developed,and young rats are prone to gastrointestinal reactions.In the third stage,the digestive system of rats has developed and matured,and no such gastrointestinal reactions have occurred.In the first stage,LW1705 can increase the area and quantity of splenic nodules in young rats’ spleens to different degrees,suggesting that administration of LW1705 at the pre-development stage of immune system may cause compensatory changes in immune organs,which can be recovered after drug withdrawal.The second and third stages LW1705 had no effect on the development of organ system.According to the results of the three stages,LW1705 can cause the levels of ALT,AST,TG and LDH to decrease and GLU to increase in each stage.In the third stage,the pH value of urine increases,which can increase the attention to the above change indexes during clinical administration,and detect the blood sugar of children to avoid the occurrence of hyperglycemia in children.LW1705 has no influence on other physiological development indexes,nerve reflex function indexes,spontaneous behavior indexes,physical sign examination and pathological examination indexes.