Modulation of aflatoxin toxicity and biomarkers by lycopene in F344 rats.
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.
Tang
Lili
L
Department of Environmental Toxicology and The Institute of Environmental and Human Health, Box 41163, Texas Tech University, Lubbock, TX 79409-1163, USA; Southern Yangtze University, Wuxi, China.
Guan
Hongxia
H
Ding
Xiaolin
X
Wang
Jia-Sheng
JS
D000080242:8-Hydroxy-2'-Deoxyguanosine; D016604:Aflatoxin B1 / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity*; D000418:Albumins / Q000737:chemistry; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D015415:Biomarkers; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity*; D002338:Carotenoids / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D006868:Hydrolysis; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D000077276:Lycopene; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D000418:Albumins; D016588:Anticarcinogenic Agents; D015415:Biomarkers; D002273:Carcinogens; D002338:Carotenoids; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D016604:Aflatoxin B1; D003849:Deoxyguanosine; D000077276:Lycopene