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1.
Toxins (Basel) ; 7(11): 4706-29, 2015 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-26569307

RESUMO

Recently, deoxynivalenol-3-sulfate (DON-3-sulfate) was proposed as a major DON metabolite in poultry. In the present work, the first LC-MS/MS based method for determination of DON-3-sulfate, deepoxy-DON-3-sulfate (DOM-3-sulfate), DON, DOM, DON sulfonates 1, 2, 3, and DOM sulfonate 2 in excreta samples of chickens and turkeys was developed and validated. To this end, DOM-3-sulfate was chemically synthesized and characterized by NMR and LC-HR-MS/MS measurements. Application of the method to excreta and chyme samples of four feeding trials with turkeys, chickens, pullets, and roosters confirmed DON-3-sulfate as the major DON metabolite in all poultry species studied. Analogously to DON-3-sulfate, DOM-3-sulfate was formed after oral administration of DOM both in turkeys and in chickens. In addition, pullets and roosters metabolized DON into DOM-3-sulfate. In vitro transcription/translation assays revealed DOM-3-sulfate to be 2000 times less toxic on the ribosome than DON. Biological recoveries of DON and DOM orally administered to broiler chickens, turkeys, and pullets were 74%-106% (chickens), 51%-72% (roosters), and 131%-151% (pullets). In pullets, DON-3-sulfate concentrations increased from jejunum chyme samples to excreta samples by a factor of 60. This result, put into context with earlier studies, indicates fast and efficient absorption of DON between crop and jejunum, conversion to DON-3-sulfate in intestinal mucosa, liver, and possibly kidney, and rapid elimination into excreta via bile and urine.


Assuntos
Galinhas/metabolismo , Micotoxinas/farmacocinética , Tricotecenos/farmacocinética , Perus/metabolismo , Animais , Biotransformação , Fezes/química , Feminino , Jejuno/química , Jejuno/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Micotoxinas/síntese química , Micotoxinas/toxicidade , Reprodutibilidade dos Testes , Sulfatos/metabolismo , Distribuição Tecidual , Tricotecenos/síntese química , Tricotecenos/toxicidade
2.
Toxins (Basel) ; 7(4): 1253-72, 2015 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-25871822

RESUMO

In chickens, the effect of mycotoxins, especially fumonisins (FB), in the gastrointestinal tract (GIT) is not well documented. Thus, this study in broiler chicks determined the effects of consuming diets prepared with Fusarium verticillioides culture material containing FB on intestinal gene expression and on the sphinganine (Sa)/sphingosine (So) ratio (Sa/So; a biomarker of FB effect due to disruption of sphingolipid metabolism). Male broilers were assigned to 6 diets (6 cages/diet; 6 birds/cage) from hatch to 20 days containing 0.4, 5.6, 11.3, 17.5, 47.8, or 104.8 mg FB/kg diet. Exposure to FB altered the Sa/So ratio in all tissues analyzed, albeit to varying extents. Linear dose-responses were observed in the kidney, jejunum and cecum. The liver and the ileum were very sensitive and data fit a cubic and quadratic polynomial model, respectively. Gene expression in the small intestine revealed low but significant upregulations of cytokines involved in the pro-inflammatory, Th1/Th17 and Treg responses, especially at 10 days of age. Interestingly, the cecal tonsils exhibited a biphasic response. Unlike the sphingolipid analysis, the effects seen on gene expression were not dose dependent, even showing more effects when birds were exposed to 11.3 mg FB/kg. In conclusion, this is the first report on the disruption of the sphingolipid metabolism by FB in the GIT of poultry. Further studies are needed to reach conclusions on the biological meaning of the immunomodulation observed in the GIT, but the susceptibility of chickens to intestinal pathogens when exposed to FB, at doses lower than those that would cause overt clinical symptoms, should be addressed.


Assuntos
Fumonisinas/farmacologia , Fusarium , Íleo/efeitos dos fármacos , Jejuno/efeitos dos fármacos , Esfingolipídeos/metabolismo , Esfingosina/análogos & derivados , Ração Animal , Animais , Galinhas , Citocinas/genética , Citocinas/metabolismo , Contaminação de Alimentos , Expressão Gênica/efeitos dos fármacos , Íleo/metabolismo , Jejuno/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Tecido Linfoide/efeitos dos fármacos , Tecido Linfoide/metabolismo , Masculino , Esfingosina/metabolismo , Proteínas Supressoras da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/metabolismo
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