Long-term Toxicity Studies Of Su Funing Lotion Bladder Perfusion In Wistar Rats

Objective:This study utilized the Wistar rats as model in vivo,to observe the toxic effect of Su Funing lotion(lyophilization)bladder perfusion on Wistar rats for 4 weeks in continuously and repeatedly.The first-occurring symptoms and their severity,toxic effects on the organs and concomitant situation of the toxic of development,and the possible reversible recovery after 2 weeks,were observed to further discover the reversibility degree of early toxic effects and the possible toxic influences.This study aims to provide first-line drug toxicology research information for the clinic.Methods:Healthy Wistar rats were choosed and then divided into 4 groups,Su Funing lotion(lyophilization)21 mg/kg,10.5 mg/kg,5.25 mg/kg,and 0.9% sodium chloride(the control group)were respectively perfused into bladder for 4 weeks.Two-thirds of the animals from each group were sacrificed 24 h after perfusion and related indicators were tested,with the remaining animals being tested and observed another 2 weeks later.The observed indicators among each groups include: general behavior,food intake,body weight,hematology,serum biochemical,viscera weight and coefficient,and indexes of histopathology.Results:1.Two rats in 5.25 mg/kg group,1 rat in 21 mg/kg group and 1 rat in control group died during 4 weeks of treatment,while animals in the 10.5 mg/kg group all survive.Nosignificant influence was observed on the general behavior,food intake and activities of any animals in this study.As no significant correlation was observed between animal death and dose amount and time,the occasional animal death can not be deduced to Su Funing lotion.2.Body weight of all animals from every group gained with time,among which,animals weight gaining of 21 mg/kg group can only be observed in the 3rd and 10 th day,statistically more slowly when compared to the control group.Statistically more slowly weight gaining was also observed in animals from 5.25 mg/kg group for 10 days,26 days,when compared to the control group.In recovery stage,only animals from 5.25 mg/kg body group gained weight more slowly than the control group,although with statistical difference but no correlation between them.3.The hematology indexes showed that 4 weeks post treatment,PLAT of 21 mg/kg,10.5 mg/kg group was higher than the control group.In the reference range.Hb,MCV,MCH of every treated group was higher than the control group.RBC of animals from 21mg/kg,5.25 mg/kg group was higher than the control group.What mentioned above suggest Su Funing lotion(lyophilization)may increase regeneration of RBC.No statistical difference was observed for the entire index above between the control and test groups.4.Detection of serum biochemistry,at the end of 4 weeks after treatment,AST,TG,TBIL of 21 mg/kg group was lower than the control group;Cl of 10.5 mg/kg group was higher than the control group,whose TC was lower than the control group,although with statistical difference,but no correlation between them.For the recovery stage,AST of 21mg/kg,10.5 mg/kg group was lower than the control group;TP of 21 mg/kg group was significant higher than the control group.Glu,Crea of 10.5 mg/kg,were both higher than the control group,although with statistical difference,but no correlation between them.5.Bone marrow test after 4 weeks of administration showed that neutral myelocyte,neutral red,rod-shaped granulocyte ratio of 21 mg/kg group was lower than the control group,neutral metamyelocyte,neutrophilic granulocyte is lower than the control group;neutral rod granulocyte,ratio of erythrocyte and myelocyte of 10.5 mg/kg group wasstatistically difference,lower than the control group,suggesting Su Funing lotion(lyophilization)may increase regeneration of RBC.No statistical difference was observed for the entire index above between the control and test groups.6.Viscera weight and Viscera coefficient index show that 4 weeks after treatment,liver weight of 21 mg/kg group was lower than the control group,brain coefficient of 21mg/kg group was higher than the control group;heart,lung,brain coefficient of 10.5mg/kg group of was higher than the control group,the kidney weight and the coefficient was higher than the control group;Thymus weight and coefficient of 5.25 mg/kg group was higher than the control group,although with statistical difference,no correlation between them.At the end of the term,no significant difference was observed in each dose group,and no statistically difference between the dose and the control group.7.Histopathological examination results show that the red marrow hyperplasia of 21mg/kg group were more active than the control group after 4 weeks with drug perfusion,which hint Su Funing lotion(lyophilization)may increase regeneration of RBC,although further test of Fisher Test suggesting no statistical difference(P ? 0.05).All of the other organ changes show no statistically difference for Fisher test(P=1).At the end of recovery stage,higher dose group showed no related histopathological changes to the test group.Conclusion:1.The dose of 21 mg/kg of Su Funing lotion(lyophilization)via continuous bladder perfusion for 4 weeks was safety for female Wister rats.2.Su Funing lotion(lyophilization)had certain effect on erythropoiesis in female Wister rats.3.Su Funing lotion(lyophilization)had certain effect on elevating blood platelet in female Wister rats.4.Su Funing lotion(lyophilization)had certain effect on reducing TG,AST,and TBIL level in female Wister rats.