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Aflatoxicol

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Gonzalo J. Diaz – 1st expert on this subject based on the ideXlab platform

  • Microsomal and cytosolic biotransformation of aflatoxin B1 in four poultry species.
    British Poultry Science, 2020
    Co-Authors: M.c. Lozano, Gonzalo J. Diaz

    Abstract:

    1. This research evaluated differences in hepatic in vitro metabolism of aflatoxin B1 (AFB1) on selected avian species. 2. Microsomal and cytosolic liver fractions were obtained from chickens, ducks, quails and turkeys; eight males and eight females of each. 3. All microsomes studied produced AFB1-8,9-exo-epoxide (AFBO), a metabolite regarded as the active product of AFB1. Turkey microsomes produced 1·8 and 3·5 times more AFBO than quails and chickens microsomes, respectively. 4. Males from evaluated birds produced more AFBO than females, but statistically-significant differences between genders were observed only in ducks and turkeys. 5. The cytosolic fraction from all four species produced Aflatoxicol (AFL). Turkey and duck hepatic cytosol produced more AFL than from quail and chickens. 6. It is known that turkeys are very sensitive to AFB1, quails are intermediate and chickens are particularly resistant; the differences in AFBO production shown in our study may help to explain the different in vivo res…

  • In vitro hepatic Aflatoxicol production is related to a higher resistance to aflatoxin B_1 in poultry
    Scientific Reports, 2020
    Co-Authors: Hansen W. Murcia, Gonzalo J. Diaz

    Abstract:

    A study was conducted to determine the cytosolic in vitro hepatic enzymatic kinetic parameters V_ m a x , K_ M , and intrinsic clearance (CL_ i n t ) for aflatoxin B_1 (AFB_1) reductase [Aflatoxicol (AFL) production] and AFL dehydrogenase (AFB_1 production) in four commercial poultry species (chicken, quail, turkey and duck). Large differences were found in AFB_1 reductase activity, being the chicken the most efficient producer of AFL (highest CL_ i n t value). Oxidation of AFL to AFB_1 showed only slight differences among the different poultry species. On average all species produced AFB_1 from AFL at a similar rate, except for the turkey which produced AFB_1 from AFL at a significantly lower rate than chickens and quail, but not ducks. Although the turkey and duck showed differences in AFL oxidation V_ m a x and K_ M parameters, their CL_ i n t values did not differ significantly. The ratio AFB_1 reductase/AFL dehydrogenase enzyme activity was inversely related to the known in vivo sensitivity to AFB_1 being highest for the chicken, lowest for the duck and intermediate for turkeys and quail. Since there is no evidence that AFL is a toxic metabolite of AFB_1, these results suggest that AFL production is a detoxication reaction in poultry. Conversion of AFB_1 to AFL prevents the formation of the AFB_1-8,9- exo -epoxide which, upon conversion to AFB_1-dihydrodiol, is considered to be the metabolite responsible for the acute toxic effects of AFB_1.

  • in vitro hepatic Aflatoxicol production is related to a higher resistance to aflatoxin b1 in poultry
    Scientific Reports, 2020
    Co-Authors: Hansen W. Murcia, Gonzalo J. Diaz

    Abstract:

    : A study was conducted to determine the cytosolic in vitro hepatic enzymatic kinetic parameters Vmax, KM, and intrinsic clearance (CLint) for aflatoxin B1 (AFB1) reductase [Aflatoxicol (AFL) production] and AFL dehydrogenase (AFB1 production) in four commercial poultry species (chicken, quail, turkey and duck). Large differences were found in AFB1 reductase activity, being the chicken the most efficient producer of AFL (highest CLint value). Oxidation of AFL to AFB1 showed only slight differences among the different poultry species. On average all species produced AFB1 from AFL at a similar rate, except for the turkey which produced AFB1 from AFL at a significantly lower rate than chickens and quail, but not ducks. Although the turkey and duck showed differences in AFL oxidation Vmax and KM parameters, their CLint values did not differ significantly. The ratio AFB1 reductase/AFL dehydrogenase enzyme activity was inversely related to the known in vivo sensitivity to AFB1 being highest for the chicken, lowest for the duck and intermediate for turkeys and quail. Since there is no evidence that AFL is a toxic metabolite of AFB1, these results suggest that AFL production is a detoxication reaction in poultry. Conversion of AFB1 to AFL prevents the formation of the AFB1-8,9-exo-epoxide which, upon conversion to AFB1-dihydrodiol, is considered to be the metabolite responsible for the acute toxic effects of AFB1.

Hansen W. Murcia – 2nd expert on this subject based on the ideXlab platform

  • In vitro hepatic Aflatoxicol production is related to a higher resistance to aflatoxin B_1 in poultry
    Scientific Reports, 2020
    Co-Authors: Hansen W. Murcia, Gonzalo J. Diaz

    Abstract:

    A study was conducted to determine the cytosolic in vitro hepatic enzymatic kinetic parameters V_ m a x , K_ M , and intrinsic clearance (CL_ i n t ) for aflatoxin B_1 (AFB_1) reductase [Aflatoxicol (AFL) production] and AFL dehydrogenase (AFB_1 production) in four commercial poultry species (chicken, quail, turkey and duck). Large differences were found in AFB_1 reductase activity, being the chicken the most efficient producer of AFL (highest CL_ i n t value). Oxidation of AFL to AFB_1 showed only slight differences among the different poultry species. On average all species produced AFB_1 from AFL at a similar rate, except for the turkey which produced AFB_1 from AFL at a significantly lower rate than chickens and quail, but not ducks. Although the turkey and duck showed differences in AFL oxidation V_ m a x and K_ M parameters, their CL_ i n t values did not differ significantly. The ratio AFB_1 reductase/AFL dehydrogenase enzyme activity was inversely related to the known in vivo sensitivity to AFB_1 being highest for the chicken, lowest for the duck and intermediate for turkeys and quail. Since there is no evidence that AFL is a toxic metabolite of AFB_1, these results suggest that AFL production is a detoxication reaction in poultry. Conversion of AFB_1 to AFL prevents the formation of the AFB_1-8,9- exo -epoxide which, upon conversion to AFB_1-dihydrodiol, is considered to be the metabolite responsible for the acute toxic effects of AFB_1.

  • in vitro hepatic Aflatoxicol production is related to a higher resistance to aflatoxin b1 in poultry
    Scientific Reports, 2020
    Co-Authors: Hansen W. Murcia, Gonzalo J. Diaz

    Abstract:

    : A study was conducted to determine the cytosolic in vitro hepatic enzymatic kinetic parameters Vmax, KM, and intrinsic clearance (CLint) for aflatoxin B1 (AFB1) reductase [Aflatoxicol (AFL) production] and AFL dehydrogenase (AFB1 production) in four commercial poultry species (chicken, quail, turkey and duck). Large differences were found in AFB1 reductase activity, being the chicken the most efficient producer of AFL (highest CLint value). Oxidation of AFL to AFB1 showed only slight differences among the different poultry species. On average all species produced AFB1 from AFL at a similar rate, except for the turkey which produced AFB1 from AFL at a significantly lower rate than chickens and quail, but not ducks. Although the turkey and duck showed differences in AFL oxidation Vmax and KM parameters, their CLint values did not differ significantly. The ratio AFB1 reductase/AFL dehydrogenase enzyme activity was inversely related to the known in vivo sensitivity to AFB1 being highest for the chicken, lowest for the duck and intermediate for turkeys and quail. Since there is no evidence that AFL is a toxic metabolite of AFB1, these results suggest that AFL production is a detoxication reaction in poultry. Conversion of AFB1 to AFL prevents the formation of the AFB1-8,9-exo-epoxide which, upon conversion to AFB1-dihydrodiol, is considered to be the metabolite responsible for the acute toxic effects of AFB1.

George S. Bailey – 3rd expert on this subject based on the ideXlab platform

  • Molecular dosimetry in fish: quantitative target organ DNA adduction and hepatocarcinogenicity for four aflatoxins by two exposure routes in rainbow trout
    Mutation Research, 1998
    Co-Authors: George S. Bailey, Roderick H. Dashwood, P.m. Loveland, Cliff Pereira, Jerry D. Hendricks

    Abstract:

    Abstract Rainbow trout, a species highly sensitive to aflatoxins, was used to investigate the relative carcinogenicities of four structurally related aflatoxins in terms of their target organ DNA binding characteristics. Tritiated syntheses were carried out, DNA binding dose–response curves were established, and liver DNA binding indices were calculated for the four aflatoxins following a 2-week dietary fry exposure protocol. The results indicated that adduct levels increased linearly with dietary dose concentration, with relative DNA binding indices of 20.7, 20.3, 2.35, and 2.22×103 (pmoles aflatoxin mg−1 DNA)/(pmoles aflatoxin g−1 diet) for aflatoxin B1 (AFB1), Aflatoxicol (AFL), aflatoxin M1 (AFM1), and Aflatoxicol M1 (AFLM1), respectively. A similar protocol used over 7200 trout fry averaging 1.2 g initial body weight to establish full carcinogen dose–response curves for each aflatoxin, along with a single-dose estimate of DNA binding index within the tumor study animals. Owing to trout sensitivity a total of 180 μg or less of each aflatoxin was required. Data analyzed on logit incidence vs. Ln dose coordinates generated four curves which were modeled as parallel in slope over most or all dose ranges studied. By this analysis, relative tumorigenic potencies were: AFB1 1.00; AFL 0.936; AFM1 0.086; and AFLM1 0.041. When data were plotted as logit incidence vs. Ln adducts (effective dose received), all aflatoxin adducts described the same dose–response curve; that is, they were equally tumorigenic, except those from AFLM1, which were 2–3 fold less potent. Therefore, by these molecular dose studies, differences in tumorigenicity among the four dietary aflatoxins are largely or entirely accounted for by differences in uptake and metabolism leading to DNA adduction, rather than any inherent differences in tumor initiating potency per DNA adduct.

  • CYP1A Induction by β-Naphthoflavone, Aroclor 1254, and 2,3,7,8-Tetrachlorodibenzo-p-dioxin and Its Influence on Aflatoxin B1Metabolism and DNA Adduction in Zebrafish (Danio rerio)
    Toxicology and Applied Pharmacology, 1997
    Co-Authors: Claudia M. Troxel, Donald R. Buhler, Jerry D. Hendricks, George S. Bailey

    Abstract:

    Abstract This study investigated the inductive response of cytochrome P4501A (CYP1A) in the zebrafish ( Danio rerio ) following exposure to Aroclor 1254, β-naphthoflavone (βNF), and 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) and then investigated TCDD modulation of aflatoxin B 1 (AFB 1 ) metabolism and hepatic AFB 1 –DNA adduction. Aroclor 1254 fed at 500 ppm for 1 to 9 days or intraperitoneal (ip) injection of 75–200 mg Aroclor 1254/kg body weight failed to induce CYP1A protein or associated 7-ethoxyresorufin- O -deethylase (EROD) activity. By contrast, dietary βNF at 500 ppm for 3 or 7 days induced CYP1A protein and EROD activity approximately threefold above controls. A single ip injection of 150 mg/kg βNF showed maximal induction of CYP1A protein and EROD activity near 24 hr, both of which decreased to control levels during the next 6 days. Single ip administration of 25, 50, 100, or 150 mg βNF/kg body weight provided dose-responsive increases in CYP1A and EROD activity. Dietary exposure to 0.75 ppm TCDD for 3 days also significantly induced CYP1A and EROD. The effect of TCDD on the metabolism of [ 3 H]AFB 1 in zebrafish was then investigated. The major [ 3 H]AFB 1 metabolites excreted in water over 24 hr in the control group were Aflatoxicol, Aflatoxicol-glucuronide, and parent AFB 1 . By contrast, the predominant metabolites in the TCDD-pretreated group were Aflatoxicol-M 1 -glucuronide, Aflatoxicol, aflatoxin M 1 plus Aflatoxicol-M 1 (unresolved), Aflatoxicol-glucuronide, and parent AFB 1 . Surprisingly, hepatic AFB 1 –DNA adduction was approximately fourfold higher in the TCDD treated group than in controls. This significant difference could not be explained by increased capacity for bioactivation of AFB 1 as measured by an in vitro AFB 1 – exo -8,9-epoxide trapping assay. However, it was demonstrated that both control and induced zebrafish have high capacity to bioactivate aflatoxin M 1 to a reactive intermediate, such that secondary bioactivation of this genotoxic intermediate may be responsible for the increased DNA binding.

  • In vivo aflatoxin B1 metabolism and hepatic DNA adduction in zebrafish (Danio rerio).
    Toxicology and Applied Pharmacology, 1997
    Co-Authors: Claudia M. Troxel, Jerry D. Hendricks, Ashok P. Reddy, Patricia E. O'neal, George S. Bailey

    Abstract:

    The zebrafish (Danio rerio) is assuming prominence in developmental genetics research. By comparison, little is known of tumorigenesis and nothing is known of carcinogen metabolism in this species. This study evaluated the ability of zebrafish to metabolize a well-characterized human carcinogen, aflatoxin B1(AFB1), to phase I and phase II metabolites and assessed hepatic AFB1–DNA adductionin vivo.Fish ip injected with 50–400 μg [3H]AFB1/kg body wt displayed a linear dose response for hepatic DNA binding at 24 hr. AFB1–DNA adduct levels among treatments showed no statistical difference over the period from 1 to 21 days after injection, suggesting poor adduct repair in this species. DNA binding in female fish was 1.7-fold higher than that in males (p< 0.01). Anin vitroAFB1metabolism assay verified that zebrafish liver extracts oxidize AFB1to the 8,9-epoxide proximate electrophile (Km= 79.0 ± 16.4 μm,Vmax= 11.7 ± 1.4 pmol/min/mg protein at 28°C). The excretion of AFB1and its metabolites was also examined by HPLC. As is typical of other fish studied, major metabolites excreted were Aflatoxicol (AFL) and Aflatoxicol–glucuronide (AFL-g), followed by unreacted AFB1. AFL appeared as early as 5 min after injection, whereas AFL-g was a significant metabolite after 18 hr. This study shows thatin vivoadministration of AFB1to zebrafish results in moderate adduction of the carcinogen to liver DNA and that zebrafish have the capacity for both phase I and phase II metabolism of AFB1. The approximate fourfold difference between rainbow trout and zebrafish AFB1–DNA covalent binding index appears insufficient to explain the relative resistance of zebrafish to dietary AFB1hepatocarcinogenicity.