Modulation of aflatoxin toxicity and biomarkers by lycopene in F344 rats.

Department of Environmental Toxicology and The Institute of Environmental and Human Health, Box 41163, Texas Tech University, Lubbock, TX 79409-1163, USA
Toxicology and Applied Pharmacology (Impact Factor: 3.63). 03/2007; 219(1):10-7. DOI: 10.1016/j.taap.2006.12.001
Source: PubMed

ABSTRACT Modulation by lycopene of aflatoxin B(1) (AFB(1))-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 AFB(1) (250 microg/kg b.w) alone. Intervention animals were administered lycopene (100 mg/kg b.w.) at 1 h following a daily treatment with AFB(1) (250 mug/kg b.w.). Pretreatment and intervention with lycopene significantly reduced the toxic effect caused by AFB(1) and greatly modulated AFB(1) metabolism and metabolic activation. Urinary excretion of AFB(1) phase 1 metabolites, AFM(1), AFQ(1), and AFP(1), was significantly decreased in lycopene-treated animals. Formation of serum AFB(1)-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 AFB(1)-DNA adducts in liver compared to control animals, with the highest reduction (52.7%) occurring on day 3 (p<0.05). Levels of AFB(1)-N(7)-guanine excreted in urine were also significantly decreased. Urinary excretion of the phase 2 detoxification metabolite, AFB(1)-mecapturic acid, was significantly increased in lycopene-intervened animals. AFB(1)-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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