Ferulic Acid Alleviates the Hepatotoxicity of Aflatoxin B1 on Broilers by Conjugating and Down-Regulating Chicken CYP1A5 and CYP2W1

Aflatoxin B1 (AFB1) induces hepatocellular damage through its metabolite aflatoxin B1-8,9-epoxide (AFBO), which is produced in endoplasmic reticulum (ER) via cytochrome P450 (CYP450) enzymes. To investigate the effect of ferulic acid (FA) on AFB1-induced broiler liver damage, one-day-old Arbor Acres broilers were exposed to AFB1 (4 mg/kg) and treated with different doses of FA (60 mg/kg, 120 mg/kg, and 240 mg/kg) continuously for 28 days. The production performance, biochemical indicators, morphological changes, CYP450 enzymes' expression in ER, interactions between small molecules and CYP450 enzymes, and CYP450 enzymes' protein secondary structure were investigated. The results showed the following: (I) FA promoted broiler growth and reduced AFBO production. (II) AFB1-induced changes in serological indicators (AST, ALT, ALP, γ-GT, TBA, TG) and biochemical parameters (GST, SOD, MDA, ROS), which were reversed by FA. (III) AFB1-induced liver morphological changes and apoptosis were obviously alleviated by FA. (IV) AFB1-induced up-regulation of CYP1A5, CYP2A6, CYP2W1, and CYP3A4 in ER were reduced by FA. (V) The binding affinity of FA to CYP1A5 is lower than that of AFB1 to CYP1A5, and the binding affinity of FA to CYP2W1 is similar to that of AFB1 to CYP2W1. (VI) The contents of α helix, β sheet, β turn, and random coil in chicken CYP1A5 were 59.6%, 7.8%, 13.6%, and 19.0% respectively, and those in chicken CYP2W1 were 32.2%, 17.1%, 16.8%, and 33.9% respectively. In conclusion, FA can promote broiler growth and alleviate AFB1-induced hepatotoxicity via inhibiting and conjugating CYP450 enzymes, thus reducing AFBO formation and oxidative damage.