The Preliminary Study Of Effects And Mechanism Of Thiamethoxam On Lipid Metabolism In Mice Liver

Neonicotinoid pesticides have replaced carbamate and organophosphate pesticides and become the most widely used pesticide category in the world.Thiamethoxam(TMX)is one of the representative agents of neonicotinoid pesticides.In previous studies,TMX was considered to be a neonicotinoid insecticide that is non-toxic to mammals.However,recent domestic and foreign literature has reported the genotoxicity,cytotoxicity and liver toxicity of TMX in mammals.But,the toxicological effect of TMX on mouse liver and its detailed mechanism have not been studied.Therefore,this project takes TMX as research object,and administers different concentrations of TMX to explore effect of TMX on the structure and function of liver tissue,analyze the lipotoxicity of TMX on mouse liver,and reveal the effect of TMX on mice.Hepatotoxicity and its molecular mechanism.In this study,adult male ICR mice were used as experimental objects,and TMX was used as experimental material.ICR mice were administered with 4 and 20 mg/kg body weight of TMX for 12 weeks.Experimental results show that exposure to TMX can cause dyslipidemia and nonalcoholic fatty 1iver disease(NAFLD).In addition,TMX treatment lead to increased liver oxidative stress and liver tissue structure and dysfunction.m RNA and protein levels showed that peroxisome proliferation-activated receptorγ(PPARγ),fatty acid synthase(FASN)and nicotinamide N-methyltransferase(NNMT)expression increase,peroxisome proliferation-activated receptorα(PPARα)and glycine-N-methyl Recombinant glycine-N-methyltransferase(GNMT)expression reduce,accompanied by a lack of S-adenosyl methionine(SAM).The results revealed that chronic TMX exposure induced abnormal lipid metabolism and NAFLD may be through NNMT-mediated methionine metabolism.To further verify this hypothesis,human liver cell line L-02 was treated b TMX and NNMT inhibitors.The results show that inhibiting NNMT can alleviate the massive accumulation of lipids in hepatocytes induced by TMX.The results indicate that TMX induces abnormal lipid metabolism and NAFLD by regulating NNMTmediated methionine metabolism,inhibiting the NNMT expression or methionine supplementation can prevent TMX-induced abnormal lipid metabolism and NAFLD occur.The results hopefully reveal potential health risks of TMX exposure and provide data support for TMX security evaluation.In addition,exploring the effects of TMX on mouse liver toxicity and its molecular mechanism has far-reaching significance for assessment of residual health risks of TMX.