| The mycotoxin Aflatoxin B1 (AFB1) has been shown to result in potent hepatotoxic and carcinogenic effects in many animal species. AFB1 undergoes metabolic conversion by cytochrome P450 (CYP) to a highly reactive AFB1-8,9-epoxide (AFBO). Turkeys are extremely sensitive to AFB1, due to a combination of efficient hepatic CYP mediated activation, and deficient glutathione S-transferase (GST) mediated detoxification of AFB1.; Butylated hydroxytoluene (BHT), a food additive, has chemoprotectant activity against many of the toxic effects of AFB1 in turkeys. This research showed that BHT acts as a competitive inhibitor of AFB 1 metabolism (Ki = 0.81 muM) in vitro, leading to significant reductions in AFBO formation in animals fed BHT as part of the diet. In vivo studies revealed that dietary addition of BHT causes reductions of AFB1 in serum, AFB1 content in selected tissues, and AFB1-DNA adduct formation. Addition of BHT to the diet also caused a significant increase in bile efflux and a nonsignificant increase in the amount of AFB1 in the bile.; Further in vivo studies found that dietary addition of BHT in conjunction with AFB1 caused some endpoints of aflatoxicosis to return to control values. At BHT concentrations as low as 100 ppm, AFB 1-induced body weight reductions were alleviated. However, serum enzyme levels and histological examination results indicate that BHT concentrations of 1000 ppm were required to return AFB1-induced toxic endpoints to control values.; The reduction in AFB1-induced toxicity is due to the ability of BHT to inhibit hepatic AFB1 activation to reactive toxic intermediate (s), and cause excretion of AFB1 at a greater rate. The observed reduction of AFB1 in serum, body tissues, and AFB1-DNA adducts indicates that activation was being inhibited in vivo. Additionally, toxic endpoints such as body weight reduction, elevated serum enzymes, and liver damage were all lessened or eliminated by dietary BHT. This research lends credence to the potential use of BHT as a supplement in animal feeds to prevent aflatoxicosis. |
