Deoxynivalenol(DON)is an inevitable contaminant in animal feed and can lead to liver damage,then decreasing appetite and causing growth retardation in piglets.Although many molecular mechanisms are related to hepatoxicity caused by DON,few studies have been done on cytochrome P450(CYP450)enzymes and DNA methylation.To explore the role of CYP450 enzymes and DNA methylation in DON-induced liver injury,male piglets were fed a control diet,or diet containing 1.0 or 3.0 mg/kg DON for 4 weeks.DON significantly raised the activity of aspartate aminotransferase(AST),alanine amino-transferase(ALT),and glutamyl transpeptidase(GGT)(P＜0.01),leading to liver injury.In vivo study found that DON exposure increased the expression of CYP450 enzymes(such as CYP1A1,CYP2E1,CYP3A29)(P＜0.05),and disturbed the expression of nicotinamide N-methyltransferase(NNMT),galanin-like peptide(GALP)and insulin-like growth factor 1(IGF-1)(P＜0.05),in which DNA methylation affected the expression of these genes.In vitro study(human normal hepatocytes L02)further proved that DON elevated the expression of CYP1A1,CYP2E1 and CYP3A4(P＜0.05),and inhibited cell growth in a dose-dependent manner,resulting in cell necrosis.More importantly,knockdown of CYP1 A1 or CYP2E1 could alleviate DON-induced growth inhibition by promoting IGF-1 expression.Taken together,increased CYP450 enzymes expression was one of the mechanisms of hepatoxicity and growth inhibition induced by DON,suggesting that the decrease of CYP450 enzymes can antagonize the hepatoxicity in animals,which provides some value for animal feed safety.

Aimei Liu;Yaqin Yang;Jingchao Guo;Yan Gao;Qinghua Wu;Ling Zhao;Lv-hui Sun;Xu Wang

National Reference Laboratory of Veterinary Drug Residues and Key Laboratory for Detection of Veterinary Drug Residues,Huazhong Agricultural University,Ministry of Agriculture(MOA),Wuhan,430070,China;MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products,Wuhan,430070,China;College of Life Science,Yangtze University,Jingzhou,434025,China;Hubei Hongshan Laboratory,College of Animal Science and Technology,Huazhong Agricultural University,Wuhan,430070,China

动物营养（英文）

[1]Aimei Liu;Yaqin Yang;Jingchao Guo;Yan Gao;Qinghua Wu;Ling Zhao;Lv-hui Sun;Xu Wang-.Cytochrome P450 enzymes mediated by DNA methylation is involved in deoxynivalenol-induced hepatoxicity in piglets)[J].动物营养（英文）,2022(02):269-279

hepatoxicity,CYP3A29,NNMT,GALP

Cytochrome,enzymes,mediated,by,methylation,involved,deoxynivalenol,induced,piglets,Deoxynivalenol,DON,inevitable,contaminant,feed,liver,damage,then,decreasing,appetite,causing,growth,retardation,Although,many,molecular,mechanisms,are,related,caused,few,studies,have,been,done,cytochrome,CYP450,To,explore,role,injury,male,were,fed,control,diet,containing,weeks,significantly,raised,activity,aspartate,aminotransferase,AST,alanine,ALT,glutamyl,transpeptidase,GGT,leading,In,vivo,study,found,that,exposure,increased,expression,such,CYP1A1,CYP2E1,disturbed,nicotinamide,methyltransferase,galanin,like,peptide,insulin,IGF,which,affected,these,genes,vitro,human,normal,hepatocytes,L02,further,proved,elevated,CYP3A4,inhibited,cell,dose,dependent,manner,resulting,necrosis,More,importantly,knockdown,could,alleviate,inhibition,promoting,Taken,together,was,suggesting,decrease,antagonize,animals,provides,some,value,safety

0.518648