Prevention of Aflatoxin B-1 Hepatoxicity by Dietary Selenium Is Associated with Inhibition of Cytochrome P450 Isozymes and Up-Regulation of 6 Selenoprotein Genes in Chick Liver

卷:146

Sun, Lv-Hui ; Zhang, Ni-Ya ; Zhu, Ming-Kun ; Zhao, Ling ; Zhou, Ji-Chang ; Qi, De-Sheng

Huazhong Agr Univ

关键词: selenium;    selenoproteins;    aflatoxin B-1;    CYP450;    chicks;   

DOI  :  10.3945/jn.115.224626

学科分类：食品科学和技术

【 摘 要 】

Background: The involvement of cytochrome P450 (CYP450) isozymes and the selenogenome in selenium-mediated protection against aflatoxin B-1 (AFB(1))-induced adverse effects in broilers remains unclear. Objective: This study was designed first to determine whether selenium could reduce AFB(1)-induced hepatotoxic effects and then to determine whether these effects were due to changes in the CYP450 isozymes and selenogenome expression in the liver of chicks. Methods: Male avian broilers (aged 120 d) were allocated to 4 groups with 5 replicates of 6 birds to be included in a 2-by-2 factorial trial in which the main factors included supplementation of AFB(1) (< 5 compared with 100 mu g/kg) and selenium (0.2 compared with 0.5 mg/kg) in a corn/soybean-based diet for 4 wk. Serum biochemistry, hepatic histology, and mRNA and/or activities of hepatic antioxidant enzymes, CYP450 isozymes, and 26 selenoproteins were analyzed at week 2 and/or 4. Results: Administration of AFB1 induced liver injury, decreasing (P < 0.05) total protein and albumin concentrations by 33.3-43.8% and increasing (P < 0.05) alanine aminotransferase and aspartate aminotransferase activities by 26.0-33.8% in serum, and induced hepatic necrosis and bile duct hyperplasia at week 2. AFB(1) also decreased (P < 0.05) hepatic activities of glutathione peroxidase (GPX), thioredoxin reductase (TXNRD), and catalase, and the glutathione concentration by 13.1-59.9% and increased (P < 0.05) malondialdehyde, 8-hydroxydeoxyguanosine and exo-AFB1-8,9-epoxide (AFBO) DNA concentrations by 17.9-1200%. In addition, themRNA and activity of enzymes responsible for the bioactivation of AFB1 into AFBO, which included CYP450 A1, 1A2, 2A6, and 3A4, were significantly induced (P < 0.05) by 29.2-271% in liver microsomes after 2-wk exposure to AFB1. These alterations induced by AFB(1) were prevented by selenium supplementation. Dietary selenium supplementation increased (P < 0.05) mRNA and/or activities of 6 selenoprotein genes (Gpx3, Txnrd1, Txnrd2, Txnrd3, iodothyronine deiodinase 2, and selenoprotein N) in the liver of AFB(1)-treated groups at week 2. Conclusions: Dietary selenium protected chicks from AFB(1)-induced liver injury, potentially through the synergistic actions of inhibition of the pivotal CYP450 isozyme-mediated activation of AFB(1) to toxic AFBO, and increased antioxidant capacities by upregulation of selenoprotein genes coding for antioxidant proteins.