Butylated Hydroxytoluene Chemoprevention of Aflatoxicosis - Effects on Aflatoxin B1 Bioavailability, Hepatic DNA Adduct Formation, and Biliary Excretion
Food and Chemical Toxicology
The extreme sensitivity of turkeys to aflatoxin B1 (AFB1) is associated with efficient hepatic cytochrome P-450 (P450)-mediated bioactivation, and deficient glutathione S-transferase (GST) mediated detoxification. Butylated hydroxytoluene (BHT) protects against AFB1 toxicity in turkeys through mechanisms that include competitive inhibition of P450-mediated AFB1 bioactivation. To test whether dietary BHT alters hepatic AFB1–DNA adduct formation, excretion, and bioavailability of AFB1 in vivo, turkeys were given diets with BHT (4000 ppm) for 10 days, given a single oral dose of [3H]-AFB1 (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 AFB1–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 M1 (AFM1) excreted in the bile was lower than in control, but BHT had no effect on the biliary excretion of AFB1, aflatoxin Q1 or glucuronide and sulfate conjugates. Thus, the chemopreventive properties of BHT may also occur through a reduction in AFB1 bioavailability in addition to inhibition of bioactivation.
Guarisco, J.A., Hall, J.O., and R.A. Coulombe, Jr. (2008) Butylated hydroxytoluene chemoprevention of aflatoxicosis - effects on aflatoxin B1 bioavailability, hepatic DNA adduct formation, and biliary excretion. Food and Chemical Toxicology 46: 3727-3731. (DOI: 10.1016/j.fct.2008.09.050)