Butylated hydroxytoluene chemoprevention of aflatoxicosis – Effects on aflatoxin B 1 bioavailability, hepatic DNA adduct formation, and biliary excretion

Abstract

The extreme sensitivity of turkeys to aflatoxin B 1 (AFB 1) is associated with efficient hepatic cytochrome P-450 (P450)-mediated bioactivation, and deficient glutathione S-transferase (GST) mediated detoxification. Butylated hydroxytoluene (BHT) protects against AFB 1 toxicity in turkeys through mechanisms that include competitive inhibition of P450-mediated AFB 1 bioactivation. To test whether dietary BHT alters hepatic AFB 1–DNA adduct formation, excretion, and bioavailability of AFB 1 in vivo, turkeys were given diets with BHT (4000 ppm) for 10 days, given a single oral dose of [ 3H]-AFB 1 (0.05 μg/g; 0.02 μCi/g), then sampled at intervals up to 24 h. Radiolabel in serum, red blood cells, liver, and breast meat was frequently lower in BHT-treated compared to control. Hepatic AFB 1–DNA adducts in BHT-treated turkeys were significantly lower at 12 and 24 h. BHT-fed birds had significant higher bile efflux, though biliary radiolabel excretion was not different from control. The amount of aflatoxin M 1 (AFM 1) excreted in the bile was lower than in control, but BHT had no effect on the biliary excretion of AFB 1, aflatoxin Q 1 or glucuronide and sulfate conjugates. Thus, the chemopreventive properties of BHT may also occur through a reduction in AFB 1 bioavailability in addition to inhibition of bioactivation.