Prevention of Aflatoxin B1 Hepatoxicity by Dietary Selenium Is Associated with Inhibition of Cytochrome P450 Isozymes and Up-Regulation of 6 Selenoprotein Genes in Chick Liver.

BACKGROUND

The involvement of cytochrome P450 (CYP450) isozymes and the selenogenome in selenium-mediated protection against aflatoxin B1 (AFB1)-induced adverse effects in broilers remains unclear.

OBJECTIVE

This study was designed first to determine whether selenium could reduce AFB1-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 AFB1 (<5 compared with 100 μg/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. AFB1 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, the mRNA 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 AFB1 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 AFB1-treated groups at week 2.

CONCLUSIONS

Dietary selenium protected chicks from AFB1-induced liver injury, potentially through the synergistic actions of inhibition of the pivotal CYP450 isozyme-mediated activation of AFB1 to toxic AFBO, and increased antioxidant capacities by upregulation of selenoprotein genes coding for antioxidant proteins.