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 aminotransferase (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 CYP1A1 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.

脱氧雪腐镰刀菌烯醇 (DON) 是动物饲料中不可避免的污染物，可导致肝损伤，进而导致仔猪食欲下降和生长迟缓。尽管许多分子机制与 DON 引起的肝毒性有关，但很少有关于细胞色素 P450 (CYP450) 酶和 DNA 甲基化的研究。为了探索 CYP450 酶和 DNA 甲基化在 DON 诱导的肝损伤中的作用，给雄性仔猪饲喂对照饮食或含有 1.0 或 3.0 mg/kg DON 的饮食 4 周。DON显着提高天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）和谷氨酰转肽酶（GGT）的活性（P  < 0.01），导致肝损伤。体内研究发现，DON 暴露增加了 CYP450 酶（如 CYP1A1、CYP2E1、CYP3A29）的表达（P < 0.05)，并扰乱了烟酰胺 N-甲基转移酶 (NNMT)、甘丙肽样肽 (GALP) 和胰岛素样生长因子 1 (IGF-1) 的表达 ( P  < 0.05)，其中 DNA 甲基化影响了这些基因。体外研究（人正常肝细胞 L02）进一步证明 DON 提高了 CYP1A1、CYP2E1 和 CYP3A4 的表达（P < 0.05)，并以剂量​​依赖性方式抑制细胞生长，导致细胞坏死。更重要的是，CYP1A1 或 CYP2E1 的敲低可以通过促进 IGF-1 表达来减轻 DON 诱导的生长抑制。综上所述，CYP450酶表达增加是DON诱导的肝毒性和生长抑制机制之一，表明CYP450酶的降低可以拮抗动物的肝毒性，这为动物饲料安全提供了一定的价值。