Study On The Mancozeb Toxic Damage And The Alleviating Effect Of Chinese Herbal Medicine Polysaccharides In Mice

Mancozeb(mancozeb,MCZ)is an ethylene didithiocarbamate fungicide,which is widely used in agriculture and industry.The wide application of MCZ brings risks to non-target organisms through a series of natural processes to pollute the environment.Exposure to MCZ can induce oxidative damage and inflammation.Anti-inflammatory and antioxidant activities are the biological activities of most traditional Chinese herbal medicine polysaccharides.In this study,through the establishment of MCZ damage model,to explore the mitigation effect and mechanism of traditional Chinese medicine polysaccharides on MCZ-induced toxicity,and to seek traditional Chinese medicine with better effect to alleviate the toxicity of MCZ.MCZ damage model test was divided into 7 groups,each group randomly assigned 106-week-old SPF Kunming mice.The blank control group was fed with 0.2mL deionized water every day,and the other 6 groups were fed with different doses of MCZ(50,100,150,200,250,300 mg/kg).After 30 days of treatment,the serum was separated,the liver and ovary were collected.The results showed that the toxicity of MCZ was dose-dependent.When the exposure dose of MCZ was 100 mg/kg,compared with the blank group,there were significant differences in body weight,ovarian index,ROS,DNMT1,DNMT3B content,DNA methylation status,ERα,ERβ level,NQO1,GcLc,HO-1 mRNA expression level(p<0.05).Uterine index,E2,FSH,LH,DNMT3A content,CAT and SOD activity were significantly different(p<0.01).These results suggest that MCZ can induce oxidative stress-induced hepatotoxicity and ovarian dysfunction,and activate Keap1-Nrf2 signal pathway.To sum up,100 mg/kg MCZ showed obvious toxic effect,so 100 mg/kg MCZ was chosen as the modeling dose.In the traditional Chinese herbal medicine polysaccharide screening test,70 mice were randomly divided into 7 groups with 10 mice in each group.The blank group was infused with 0.2mL deionized water twice a day,the MCZ model group was infused with 100mg/kg MCZ and 0.2mL deionized water every day,and the traditional Chinese medicine polysaccharide treatment group was infused with 100mg/kg MCZ and 200mg/kg Lycium barbarum polysaccharides(LBP),Astragalus polysaccharide(APS),Glycyrrhiza polysaccharide(GP),Cuscuta chinedsis polysaccharides(CCP)and Chinese Yam Polysaccharide(CYPS),respectively.The rats were killed after 30 days of treatment,and the blood,uterus and ovaries were collected.The results showed that all the above five polysaccharides could alleviate the damage of MCZ,among which GP had the best effect.Compared with model group(MCZ),there were significant differences in body weight,CAT activity,contents of LH,ERβ,ERα and mRNA expressions of HO-1,GCLC,NQO1 and GPX2 in GP group(p<0.05).There were significant differences in ovarian index,uterine index,SOD activity,MDA content and GSTT2 mRNA expression(p<0.01).To sum up,GP has the best effect on the remission of ovarian toxicity induced by MCZ.According to traditional Chinese medicine,there is an indirect or direct relationship between liver and ovarian function.Therefore,in this study,GP was selected to explore the mechanism of relieving hepatotoxicity induced by MCZ.In GP treatment test,70 mice were randomly divided into 7 groups(A,B,C,D,E,F,G),A were given 0.2 mL deionized water twice a day,group B was given 100 mg/kg MCZ and 0.2 mL deionized water twice a day,group C,D,E and F were fed with 100 mg/kg MCZ and 200 mg/kg,150 mg/kg,100 mg/kg GP and 100 mg/kg Vc,respectively.After 30 days of treatment,the mouse were killed and the blood and liver were collected.The results showed that compared with group B(MCZ model group),mice in groups C,D,E,and F had a significant increase(p<0.01)in their final body weight and GSH-PX activity,SOD activity in group C,and MDA content in group F;the liver index and MDA content of mice in groups D and E,the activity of CAT and the content of MDA in group C;the expressions of Keap1,Nrf2 and NF-κB in the liver of mice in groups C,D,E,and F were extremely significantly reduced(p<0.01).After applying GP,The mRNA expression of Keap1-Nrf2/NF-κB pathway related genes was also different from that in group B.The results showed that GP could activate Keap1-Nrf2/NF-κB pathway to alleviate oxidative stress and inflammation induced by MCZ.