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: 3.71). 03/2007; 219(1):10-7. DOI: 10.1016/j.taap.2006.12.001
Source: PubMed


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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    • "Lycopene (LYC) is a ''nonprovitamin A carotenoid'' (Aydin and C ¸ elik 2012). The chemical structure of LYC (Fig. 1) has a 40-carbon acyclic carotenoid with 11 linearly arranged conjugated double bonds (Tang et al. 2007). LYC is one dietary carotenoid found in fruits such as papaya, fresh ripe tomato, guava, grapefruit and watermelon (Yaping et al. 2002). "
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    ABSTRACT: There is a very little information about the protective effect of lycopene (LYC) against hepatic ischemia-reperfusion injury. The present study was designed to examine the possible protective effect of the strong antioxidant and anti-inflammatory agent, LYC, on hepatic ischemia/reperfusion injury. For this purpose, rats were subjected to 45 min of hepatic ischemia followed by 60 min of reperfusion period. LYC at the doses of 2.5 and 5 mg/kg body weight (bw) were injected intraperitoneally, 60 min prior to ischemia. Upon sacrification, hepatic tissue samples were used for the measurement of catalase (CAT) activity and malondialdehyde (MDA) levels. Also, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were assayed in serum samples. As a result of the use of LYC at the doses of 2.5 and 5 mg/kg bw; while improvements of the ALT, AST, LDH and MDA values were partial and dose-dependent, the improvement of CAT activity was total and dose-independent (p < 0.05). Our findings suggest that LYC has a protective effect against ischemia/reperfusion injury on the liver.
    Cytotechnology 03/2014; 67(3). DOI:10.1007/s10616-014-9706-3 · 1.75 Impact Factor
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    • "Lycopene and silymarin as recently most popular antioxidant compounds were tested at 100 mg/kg whether they have any effect on hepatic functions and oxidative/ antioxidative status. Although the bioavailability of lycopene was very low (1–3% absorbed) in animals, it was found to be concentrated in various body tissues, such as the liver, adrenals, and adipose tissue [2]. Lycopene molecule has been shown [25] to be absorbed with having similar tissue distribution in rats and humans, therefore rats were chosen as an appropriate animal model for assessing the potential effects of lycopene in humans. "
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    ABSTRACT: Objective: To evaluate effects of lycopene and silymarin on antioxidant enzymes, lipid peroxidation and possible liver toxicity in rats. Methods: 15 female Wistar rats were divided into 3 groups: control group (Group I) received corn oil while Groups II and III were treated with 100 mg/kg oral dose of lycopene and silymarin for 7 days, respectively. The antioxidant enzyme activities of liver (superoxide dismutase and catalase) and malondialdehyde level were measured. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), cholesterol and urea levels were also analyzed. Besides, histopathological evaluations were performed in liver. Results: Silymarin treatment resulted in significant decreases in catalase and cholesterol and increase in superoxide dismutase activities compared to control, while lycopene caused significant decrease in urea levels. Both of the antioxidants caused an increase in liver function enzymes AST and ALT compared to the control group. In lycopene treated group, ALP levels were also increased in comparison with control. There were significant differences in cholesterol, AST and ALP levels between silymarin and lycopene treatment groups. In histopathological examinations minimal changes were observed in liver tissues. Conclusion: Lycopene and silymarin treatment may cause alterations in liver functions due to the dose and/or duration. Therefore, both of the lycopene and silymarin need to be investigated in detail for their possible beneficial and harmful effects.
    Turkish Journal of Biochemistry 01/2014; 39(3):344-350. DOI:10.5505/tjb.2014.17136
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    • "One mechanism is that lycopene may stabilize lipid membranes and protect LPO by free radical scavenging mechanism, thereby protecting tissues. Alternatively, lycopene may induce hepatocellular metabolic enzymes (Tang et al., 2007) for PCBs, consequently protecting tissues against PCBs-induced toxicity. "
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    ABSTRACT: Sertoli cell proliferation is attenuated before attaining puberty and the number is fixed in adult testes. Sertoli cells determine both testis size and daily sperm production by providing physical and metabolic support to spermatogenic cells. Polychlorinated biphenyls (PCBs) exposure disrupts functions of Sertoli cells causing infertility with decreased sperm count. On the other hand, lycopene is improving sperm count and motility by reducing oxidative stress in humans and animals. Hence we hypothesized that PCBs-induced infertility might be due to Sertoli cell apoptosis mediated by oxidative stress and lycopene might prevent PCBs-induced apoptosis by acting against oxidative stress. To test this hypothesis, animals were treated with vehicle control, lycopene, PCBs and PCBs + lycopene for 30 days. After the experimental period, the testes and cauda epididymidis were removed for isolation of Sertoli cells and sperm, respectively. We observed increased levels of oxidative stress markers (H2O2 and LPO) levels, increased expression of apoptotic molecules (caspase-8, Bad, Bid, Bax, cytochrome C and caspase-3), decreased anti-apoptotic (Bcl2) molecule and elevated apoptotic marker activity (caspase-3) in Sertoli cells of PCBs-exposed animals. These results were associated with decreased sperm count and motility in PCBs exposed animals. On the other hand, lycopene prevented the elevation of Sertoli cellular apoptotic parameters and prevented the reduction of sperm parameters (count and motility). The data confirmed that lycopene as an antioxidant scavenged reactive oxygen substances, prevented apoptosis, maintained normal function in Sertoli cells and helped to provide physical and metabolic support for sperm production, thereby treating infertility in men.
    Interdisciplinary toxicology 06/2013; 6(2):83-92. DOI:10.2478/intox-2013-0015
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