| The total alkaloids of Macleaya tomentosa are a kind of alkaloids extracted from Macleaya tomentosa.The main components are sanguinarine,chelerythrine,proopioid and allopine,which have the effects of promoting growth,improving immunity,sterilization and anti-tumor.Clinically,it is mainly used as animal feeding additive,but the total alkaloid of Macleaya cordata has a certain toxic effect.In order to avoid the toxic effect in production and application,this experiment was carried out.This Graduate thesis mainly studies the toxicity of the total alkaloid of Macleaya cordata to pregnant and fetal mice and the reproductive toxicity of Bordeaux Powder,which is made from the total alkaloid of Macleaya cordata as raw material,to breeder eggs.According to the literature and previous studies,the following experiments were carried out in three groups of pregnant mice exposed to total alkaloids of Macleaya cordata at 10,20,40 mg/kg and three laying breeder hens exposed to Bopusan at 400,1200 and 2000 mg/kg respectively.1.Toxicity Test of Total Alkaloids of Macleaya cordata on Wistar Fetal mice 48 healthy Wistar pregnant rats were divided into 4 groups with 12 rats in each group:low,middle and high dose exposure groups and blank control group.On the 7-16 day of gestation,the pregnant rats in the treatment group were given different doses of cordata total alkaloid suspension(100g.mL-1d-1)according to their body weight,and the blank control group was given the corresponding dose of normal saline according to their body weight.After the end of pregnancy,the anaesthetized pregnant rats were given caesarean section to take out fetal rats and related organs of pregnant rats,weigh the uterine weight and fetal weight of pregnant rats,and count the total number of fetal rats,the number of live fetuses,the number of dead fetuses and the number of absorbed fetuses,and measure the body length and tail length of fetal rats.fetal rat appearance,fetal rat visceral bone deformity examination.The results showed that the uterine weight of pregnant rats in the high dose group was the lightest,and the live fetal survival rate was only 2.56%,which was significantly lower than that in the other groups(P<0.05).There was no significant difference in fetal survival rate among blank control group?low dose group and middle dose group(P>0.05).They were 98.15%,96.44%and 91.42%respectively;and there was no significant difference in fetal weight,fetal body length and tail length(P>0.05).Because there was no fetal mouse in the high dose group,there was significant difference(P<0.05),so only the middle dose group and low dose group were statistically compared.The visceral deformity rate of fetal rats in the middle dose group was 26.21%,which was significantly higher than 7.00%and 10.21%in the blank control group and low dose group,and there was significant difference between the middle dose group and the blank control group(P<0.05).There was no significant difference in the bone deformity rate among the three groups.The results showed that the low dose(10 mg/kg)of total alkaloids of Macleaya cordata had no embryotoxicity to fetal mice,while the middle dose(20 mg/kg)had certainly embryotoxicity,which mainly caused visceral malformation in fetal mice,while the high dose(40 mg/kg)had serious embryotoxicity,which mainly caused fetal development disturbance,resulting in stillbirth and abortion.Therefore,it can be concluded that the maximum non-toxic dose(NOEL)of Cornus officinalis total alkaloid suspension is 10 mg/kg body weight The lowest toxic dose((LOEL))was 20 mg/kg body weight2.Toxicity Test of Total Alkaloids of Macleaya cordata on Wistar pregnant mice 48 healthy Wistar pregnant rats were divided into 4 groups with 12 rats in each group low,middle and high dose of Macleaya cordata alkaloids exposure group and blank control group.The toxicity test of Macleaya cordata total alkaloids on Wistar pregnant rats was carried out in 48 healthy Wistar pregnant rats,and were divided into 4 groups with 12 rats in each group.On the 7-16 day of gestation,the pregnant rats in the treatment group were given different doses of cordata total alkaloid suspension(100g.mL-1d-1)according to their body weight,and the blank control group was given the corresponding dose of normal saline according to their body weight.The amount of food intake and water intake of pregnant rats were recorded every day during the whole pregnancy.After the end of pregnancy,the dead pregnant rats were anesthetized,and the blood was collected and related pathological examination was done.The results showed that there was no significant difference in feed intake,water intake and body weight among the four groups,and no histopathological toxicity changes were found in serum biochemical indexes and paraffin sections of liver and kidney tissues among the four groups.the results showed that the high,middle and low doses of total alkaloids of Cortex cordata had no hepatotoxicity and no significant effect on the growth of pregnant rats.However,through the observation of uterine and ovarian tissue sections of pregnant rats,it was found that the middle and high doses of total alkaloids had toxic effects on the uterus and ovaries of pregnant rats,which could make the myometrium of uterine wall thinner,endometrium damaged and follicular dysplasia.Granulosa cells in follicles decreased.The content of serum estrogen in the middle dose group and high dose group was significantly lower than that in the blank control group(P<0.05),but there was no significant change in follicle stimulating hormone and luteinizing hormone.The content of progesterone in the high dose group was the lowest,followed by the middle dose group.The blank control group was the highest,but there was no significant difference among the four groups(P>0.05).The results suggested that the toxicity test of the total alkaloids of Macleaya cordata on Wistar pregnant rats showed that the middle dose(20 mg/kg)and high dose(40 mg/kg)of the total alkaloids of Macleaya cordata had no obvious toxicity to the pregnant rats,and the maximum non-toxic dose(NOEL)could be determined as 40 mg/kg body weight.However,it can reduce the content of reproductive hormones,especially estradiol,in pregnant rats by inhibiting the development of ovaries,thus producing toxic effects on the development of fetal rats3.Reproductive toxicity of Bopusan to breeder eggs Reproductive toxicity of Bopusan to breeder hens 80 breeder hens at the late peak of egg production were randomly divided into 4 groups:blank control group,low dose group(400 mg/kg),middle dose group(1200 mg/kg)and high dose group(2000 mg/kg).Different doses of Bopusan(the content of total alkaloids in Macleaya cordata>1.5%)were mixed for 10 days,and the observation period was 16 days.The reproductive toxicity of Bopusan to breeder eggs was judged by observing the laying rate,egg quality,fertilization rate,hatching rate,health status and body weight of breeding hens at 0-1 d,9-10 d and 5-6 d after drug withdrawal.The results showed that the low,middle and high dose groups had no reproductive toxicity to breeder hens,and had no effect on the body weight,laying rate and egg quality of breeder chickens compared with the blank control group,but also increased the fertilization rate and hatching rate of breeder eggs to a certain extent,indicating that even high dose group(2000 mg/kg)Bopusan not only had no production toxicity to breeder chickens,but also could improve the fertilization rate and hatching rate of breeder eggs.It is helpful to the breeding of breeder chickens.The reproductive toxicity test of total alkaloids of Macleaya cordata showed that the lowest toxic dose(LOEL)was 20 mg/kg body weight,which mainly caused visceral developmental malformation in some fetal mice,while the 40 mg/kg body weight dose had serious embryonic toxicity,which mainly caused fetal development disturbance,resulting in stillbirth and abortion.The toxic mechanism may be related to the inhibition of ovarian development and the reduction of reproductive hormones,especially estradiol,in pregnant rats.The toxicity test of the total alkaloids of Macleaya cordata on Wistar pregnant rats showed that the maximum non-toxic dose of the total alkaloids of Macleaya cordata((NOEL))was 40 mg/kg body weight.The toxicity test of breeder eggs showed that Bopusan had high safety to breeder eggs,and the maximum non-toxic dose(NOEL)was 2000 mg/kg,.It could be safely used according to the recommended dose(400mg/kg)in clinic. |
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