Modulation of aflatoxin toxicity and biomarkers by lycopene in F344 rats

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Modulation by lycopene of aflatoxin B1 (AFB1)-induced toxic effects, metabolism, and metabolic activations was studied in young F344 rats. Animals were pretreated orally with either corn oil (control group) or lycopene [100 mg/kg body weight (b.w.), intervention group] 5 days/week for 2 weeks. Control animals were then treated daily with AFB1 (250 μg/kg b.w) alone. Intervention animals were administered lycopene (100 mg/kg b.w.) at 1 h following a daily treatment with AFB1 (250 μg/kg b.w.). Pretreatment and intervention with lycopene significantly reduced the toxic effect caused by AFB1 and greatly modulated AFB1 metabolism and metabolic activation. Urinary excretion of AFB1 phase 1 metabolites, AFM1, AFQ1, and AFP1, was significantly decreased in lycopene-treated animals. Formation of serum AFB1–albumin adducts was also significantly reduced. The rate of reduction was from approximately 30% on day 1 (p < 0.05) to 67.7% on day 15 (p < 0.001). Lycopene intervention also significantly reduced formation of AFB1–DNA adducts in liver compared to control animals, with the highest reduction (52.7%) occurring on day 3 (p < 0.05). Levels of AFB1–N7-guanine excreted in urine were also significantly decreased. Urinary excretion of the phase 2 detoxification metabolite, AFB1–mecapturic acid, was significantly increased in lycopene-intervened animals. AFB1-induced urinary excretion of 8-hydroxydeoxyguanosine was also reduced to 50% on day 7 after lycopene intervention. Collectively, these results suggest that inhibition of phase 1 metabolism and metabolic activation, as well as induction of phase 2 detoxification enzyme activity are the potential mechanisms for the chemopreventive effects of lycopene.

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