RESUMO
The pathophysiology of type 2 diabetes mellitus (T2D) is characterized by reduced or absent insulin receptor (INSR) responsiveness to its ligand, elevated hepatic glucose output and impaired glucose uptake in peripheral tissues, particularly skeletal muscle. Treatments to reduce hyperglycemia and reestablish normal insulin signaling are much sought after. Any agent which could be orally administered to restore INSR function, in an insulin-independent manner, would have major implications for the management of this global disease. We have discovered a non-peptidyl small molecule, adenosine, 5'-Se-methyl-5'-seleno-, 2',3'-diacetate [referred to as non-peptidyl compound #43 (NPC43)], which restores INSR signaling in the complete absence of insulin. Initial screening of numerous compounds in human HepG2 liver cells revealed that NPC43 significantly inhibited glucose production. The compound was potently anti-hyperglycemic and anti-hyperinsulinemic in vivo, in insulin-resistant T2D Leprdb/db mice, following either acute or chronic treatment by oral gavage and intraperitoneal injection, respectively. The compound acted at the level of INSR and activated it in both liver and skeletal muscle of Leprdb/db mice. In cell culture, the compound activated INSR in both liver and skeletal muscle cells; furthermore, it cooperated with insulin to depress glucose-6-phosphatase catalytic subunit (G6pc) expression and stimulate glucose uptake, respectively. Our results indicated that the compound directly interacted with INSRα, triggering appropriate phosphorylation and activation of the receptor and its downstream targets. Unlike insulin, NPC43 did not activate insulin-like growth factor 1 receptor in either liver or skeletal muscle. We believe this compound represents a potential oral and/or injectable insulin replacement therapy for diabetes and diseases associated with insulin resistance.
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Adenosina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Receptor de Insulina/metabolismo , Adenosina/análogos & derivados , Animais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Células Hep G2 , Humanos , Hiperglicemia/complicações , Hiperglicemia/metabolismo , Hipoglicemiantes/química , Insulina/metabolismo , Resistência à Insulina , Masculino , Metilação , Camundongos , Camundongos Endogâmicos C57BL , Compostos Organosselênicos/química , Compostos Organosselênicos/uso terapêuticoRESUMO
Deoxynivalenol (DON) is one of the most common mycotoxins in animal feed worldwide and causes significant threats to the animal health. Increased use of plant ingredients in aquaculture feeds increased the risk of mycotoxin contamination. To evaluate the effects of dietary deoxynivalenol (DON) on growth performance, immune response and intestinal health of turbot and the mitigation efficacy of yeast cell wall extract (YCWE) toward DON, nine isonitrogenous and isolipidic diets were formulated: Diet 1 (control): No DON added; Diets 2-5 or Diets 6-9: 0.5 or 3.0 mg added DON/kg diet + 0%, 0.1%, 0.2%, or 0.4% YCWE, respectively. Results showed that Diet 6 (3 mg/kg DON, 0% YCWE) significantly decreased weight gain, specific growth rate and feed efficiency ratio of fish and reduced immunoglobulin M and complement 4 concentrations in serum. Fish fed Diet 6 presented morphological alterations, lower activity of superoxide dismutase, catalase and total antioxidant capacity but higher malondialdehyde content, lower claudin-4 and occludin expression but higher interleukin-1ß expression in intestine. Besides, Diet 6 decreased the abundance of potential helpful bacteria but increased the abundance of potential pathogens in intestine. While, dietary YCWE, especially Diet 8 (3 mg/kg DON, 0.2% YCWE) and 9 (3 mg/kg DON, 0.4% YCWE), markedly improved growth performance and immune response and enhanced the intestinal health of turbot. In conclusion, dietary YCWE could mitigate the toxic effects induced by DON in turbot, and could be used as an effective strategy to control DON contamination in fish feed.
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The global popularity of chicken in human diets make it an obvious choice for enrichment with DHA and LC-PUFA. There is presently a need for a robust method for the analysis of chicken tissues and where the fitness for purpose of the method has been demonstrated. The purpose of this paper is to present the validation of the AOAC method 996.06 on five different chicken tissues; breast, thigh, skin, kidney and liver. The parameters investigated as part of the validation study included; linearity and range, the limit of detection and limit of quantification, accuracy, repeatability, inter-analyst reproducibility, and specificity. The method was further applied to assess the stability of DHA and other specific LC-PUFA in chicken tissues over short and long timepoints. The disclosure of this information is relevant for researchers concerned with the analysis of LC-PUFA in regulatory and efficacy studies.
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Galinhas/metabolismo , Ácidos Graxos Insaturados/farmacocinética , Animais , Ácidos Graxos Insaturados/análise , Distribuição TecidualRESUMO
Docosahexaenoic acid (DHA), is an omega 3 fatty acid (n-3 FA) that has been shown to play a role in canine growth and physiological integrity and improvements in skin and coat condition. However, potential adverse effects of n-3 FA specifically, impaired cellular immunity has been observed in dogs fed diets with elevated levels of n-3 FA. As such, a safe upper limit (SUL) for total n-3 FAs (DHA and EPA) in dogs has been established. Considering this SUL, sensitive methods detecting DHA in blood serum as a biomarker when conducting n-3 FA supplementation trials involving dogs are required. In this study, an LC-ESI-MS/MS method of DHA detection in dog serum was validated and verified. Recovery of DHA was optimized and parallelism tests were conducted with spiked samples demonstrating that the serum matrix did not interfere with quantitation. The stability of DHA in serum was also investigated, with -80⯰C considered suitable when storing samples for up to six months. The method was linear over a calibration range of 1-500⯵g/mL and precision and accuracy were found to meet the requirements for validation. This method was verified in an alternative laboratory using a different analytical system and operator, with the results meeting the criteria for verification.
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Ácidos Docosa-Hexaenoicos/sangue , Animais , Cromatografia Líquida , Cães , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em TandemRESUMO
Penicillium mycotoxins (PMs) are toxic contaminants commonly found as mixtures in animal feed. Therefore, it is important to investigate potential joint toxicity of PM mixtures. In the present study, we assessed the joint effect of binary combinations of the following PMs: citrinin (CIT), ochratoxin A (OTA), patulin (PAT), mycophenolic acid (MPA) and penicillic acid (PA) using independent action (IA) and concentration addition (CA) concepts. Previously published toxicity data (i.e. IC25; PM concentration that inhibited bovine macrophage (BoMacs) proliferation by 25%) were initially analyzed, and both concepts agreed that OTA+PA demonstrated synergism (p<0.05), while PAT+PA showed antagonism (p<0.05). When a follow-up dilution study was carried out using binary combinations of PMs at three different dilution levels (i.e. IC25, 0.5∗IC25, 0.25∗IC25), only the mixture of CIT+OTA at 0.5∗IC25 was determined to have synergism by both IA and CA concepts with Model Deviation Ratios (MDRs; the ratio of predicted versus observed effect concentrations) of 1.4 and 1.7, respectively. The joint effect of OTA+MPA, OTA+PA and CIT+PAT complied with the IA concept, while CIT+PA, PAT+MPA and PAT+PA were better predicted with the CA over the IA concept. The present study suggests to test both IA and CA concepts using multiple doses when assessing risk of mycotoxin mixtures if the mode of action is unknown. In addition, the study showed that the tested PMs could be predicted by IA or CA within an approximate two-fold certainty, raising the possibility for a joint risk assessment of mycotoxins in food and feed.
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Antibacterianos/metabolismo , Citrinina/metabolismo , Macrófagos/metabolismo , Micotoxinas/metabolismo , Ocratoxinas/metabolismo , Penicillium/metabolismo , Animais , Antibacterianos/química , Antibacterianos/toxicidade , Bovinos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Citrinina/química , Citrinina/toxicidade , Relação Dose-Resposta a Droga , Interações Medicamentosas/fisiologia , Macrófagos/efeitos dos fármacos , Micotoxinas/química , Micotoxinas/toxicidade , Ocratoxinas/química , Ocratoxinas/toxicidade , Penicillium/químicaRESUMO
A random-effects meta-analysis was conducted to investigate the effect of mycotoxins (MT) without or with the inclusion of yeast cell wall extract (YCWE, Mycosorb®, Alltech, Inc., Nicholasville, KY, USA) on laying hen performance. A total of 25 trials were collected from a literature search, and data were extracted from 8 of these that met inclusion criteria, for a total of 12 treatments and 1774 birds. Laying hens fed MT had lower (p < 0.05) body weight (BW) by -50 g, egg production by -6.3 percentage points, and egg weight by -1.95 g than control fed hens (CTRL). Inclusion of YCWE during the mycotoxin challenges (YCWE + MT) resulted in numerically greater (p = 0.441) BW by 12.5 g, while egg production and egg weight were significantly (p < 0.0001) higher by 4.2 percentage points and 1.37 g, respectively. Furthermore, economic assessment calculations indicated that YCWE may not only support hen performance but also resulted in a positive return on investment. In conclusion, mycotoxins can play a role in negatively impacting laying hen performance and profitability. Inclusion of YCWE in feed with mycotoxin challenges provided benefits to egg production and egg weight and may support profitability. As such, the inclusion of YCWE could play an important role in minimizing mycotoxin effects and in turn aid farm efficiency and profitability.
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Ração Animal , Parede Celular , Galinhas , Micotoxinas , Animais , Micotoxinas/toxicidade , Parede Celular/efeitos dos fármacos , Feminino , Leveduras , Reprodução/efeitos dos fármacos , Suplementos NutricionaisRESUMO
Frequently reported occurrences of deoxynivalenol (DON), beauvericin (BEA), and, to a lesser extent, ochratoxin A (OTA) and citrinin (CIT) in ruminant feed or feedstuff could represent a significant concern regarding feed safety, animal health, and productivity. Inclusion of yeast cell wall-based mycotoxin adsorbents in animal feeds has been a common strategy to mitigate adverse effects of mycotoxins. In the present study, an in vitro approach combining adsorption isotherm models and bioassays was designed to assess the efficacy of yeast cell wall (YCW), yeast cell wall extract (YCWE), and a postbiotic yeast cell wall-based blend (PYCW) products at the inclusion rate of 0.5% (w/v) (ratio of adsorbent mass to buffer solution volume). The Hill's adsorption isotherm model was found to best describe the adsorption processes of DON, BEA, and CIT. Calculated binding potential for YCW and YCWE using the Hill's model exhibited the same ranking for mycotoxin adsorption, indicating that BEA had the highest adsorption rate, followed by DON and CIT, which was the least adsorbed. PYCW had the highest binding potential for BEA compared with YCW and YCWE. In contrast, the Freundlich isotherm model presented a good fit for OTA adsorption by all adsorbents and CIT adsorption by PYCW. Results indicated that YCW was the most efficacious for sequestering OTA, whereas YCWE was the least efficacious. PYCW showed greater efficacy at adsorbing OTA than CIT. All adsorbents exhibited high adsorption efficacy for BEA, with an overall percentage average of bound mycotoxin exceeding 60%, whereas moderate efficacies for the other mycotoxins were observed (up to 37%). Differences in adsorbent efficacy of each adsorbent significantly varied according to experimental concentrations tested for each given mycotoxin (p < 0.05). The cell viability results from the bioassay using a bovine mammary epithelial cell line (MAC-T) indicated that all tested adsorbents could potentially mitigate mycotoxin-related damage to bovine mammary epithelium. Results from our studies suggested that all tested adsorbents had the capacity to adsorb selected mycotoxins in vitro, which could support their use to mitigate their effects in vivo.
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Micotoxinas , Fermento Seco , Animais , Bovinos , Micotoxinas/toxicidade , Saccharomyces cerevisiae , Ração Animal/análise , Parede Celular , AdsorçãoRESUMO
High incidence of traditional and emerging Fusarium mycotoxins in cereal grains and silages can be a potential threat to feed safety and ruminants. Inadequate biodegradation of Fusarium mycotoxins by rumen microflora following ingestion of mycotoxin-contaminated feeds can lead to their circulatory transport to target tissues such as mammary gland. The bovine udder plays a pivotal role in maintaining milk yield and composition, thus, human health. However, toxic effects of Fusarium mycotoxins on bovine mammary gland are rarely studied. In this study, the bovine mammary epithelial cell line was used as an in-vitro model of bovine mammary epithelium to investigate effects of deoxynivalenol (DON), enniatin B (ENB) and beauvericin (BEA) on bovine mammary gland homeostasis. Results indicated that exposure to DON, ENB and BEA for 48 h significantly decreased cell viability in a concentration-dependent manner (P < 0.001). Exposure to DON at 0.39 µmol/L and BEA at 2.5 µmol/L for 48 h also decreased paracellular flux of FITC-40 kDa dextran (P < 0.05), whereas none of the mycotoxins affected transepithelial electrical resistance after 48 h exposure. The qPCR was performed for assessment of expression of gene coding tight junction (TJ) proteins, toll-like receptor 4 (TLR4) and cytokines after 4, 24 and 48 h of exposure. DON, ENB and BEA significantly upregulated the TJ protein zonula occludens-1, whereas markedly downregulated claudin 3 (P < 0.05). Exposure to DON at 1.35 µmol/L for 4 h significantly increased expression of occludin (P < 0.01). DON, ENB and BEA significant downregulated TLR4 (P < 0.05). In contrast, ENB markedly increased expression of cytokines interleukin-6 (IL-6) (P < 0.001), tumor necrosis factor α (TNF-a) (P < 0.05) and transforming growth factor-ß (TGF-ß) (P < 0.01). BEA significantly upregulated IL- 6 (P < 0.001) and TGF-ß (P = 0.01), but downregulated TNF-α (P < 0.001). These results suggest that DON, ENB and BEA can disrupt mammary gland homeostasis by inducing cell death as well as altering its paracellular permeability and expression of genes involved in innate immune function.
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Using a random-effects meta-analysis, the performance of growing pigs under a mycotoxin challenge (MT) with or without supplementation of yeast cell wall extract (YCWE, Mycosorb®, Alltech Inc.) was evaluated. Both MT and YCWE were also compared to animal controls not receiving mycotoxins (CTRL). Meta-regression was used to further explore the impacts of MT at/below (category 1) or above (category 2) global regulatory guidelines. Following the screening, 23 suitable references (30 mycotoxin treatments) were used. Overall, MT lowered average daily gain (ADG, p < 0.001) and average daily feed intake (ADFI, p < 0.0001) from CTRL by -84 and -165 g, respectively. Inclusion of YCWE during mycotoxin challenges (YCWE+MT, average 2.1 kg/ton) tended to result in greater ADG (+17 g, p = 0.068) compared to MT treatments. The gain-to-feed ratio (G:F) was not impacted by MT or YCWE+MT. Further investigation by meta-regression revealed that pigs fed MT in category 1 had lower ADG (-78.5 g, p < 0.001) versus CTRL, while YCWE+MT had higher ADG (+48 g, p < 0.001) over MT and was similar to CTRL. The ADFI was not impacted, although YCWE+MT had ADFI values similar to the CTRL. In category 2, ADG and ADFI of pigs fed MT were lower than CTRL (-85.1 and -166 g, respectively, p < 0.0001), with a tendency for YCWE+MT to result in higher ADFI (+25.3 g, p = 0.062). In summary, the inclusion of YCWE provided benefits to performance during common mycotoxin challenge levels (at or below regulatory guidelines).
Assuntos
Micotoxinas , Animais , Suínos , Micotoxinas/toxicidade , Micotoxinas/análise , Saccharomyces cerevisiae , Ingestão de Alimentos , Ração Animal/análise , Parede Celular/química , Extratos Vegetais , DietaRESUMO
RATIONALE: Mycotoxins are typically present in grain and are also concentrated in distillers dried grains with solubles (DDGS), common feed ingredients for food animals. The diversity of mycotoxins and feed matrices has made the routine detection and quantification of mycotoxins in feed both complex and prohibitively expensive. METHODS: Ultra-performance liquid chromatography/electrospray ionization triple quadrupole detection (UPLC/ESI-TQD) (tandem mass spectrometry, MS/MS) with (13) C-labeled isotopic dilution was used to analyze internal standard isotopologues of three mycotoxin molecules, as well as 29 other structurally differing mycotoxin molecules from four common feed matrices: corn, wheat, barley, or DDGS. Mycotoxins were extracted via a single-step procedure using a mixture of acetonitrile/water/formic acid. Labeled isotopologues were used as a surrogate to account for extraction quality and as internal standards for the evaluation of the feed matrix signal suppression/enhancement (SSE) contributed by each mycotoxin and by each matrix. The SSE was corrected by matrix-matched calibration with blank certified reference feed material. RESULTS: The limits of detection for individual mycotoxins in buffer ranged from 0.01 to 206.7 µg/mL but could increase by up to four times depending on the matrix effect. The accuracy and precision were enhanced by the use of isotopically labeled standards. The recoveries were somewhat negatively affected by the SSE contributed by each matrix. Each mycotoxin was successfully detected and assigned to one of four SSE categories: high (-66%), intermediate (-48%), low (-19%) signal suppression and signal enhancement (> +300%). CONCLUSIONS: An improved LC/MS method was validated, which offers a practical and economical means for large-scale detection and quantification of multiple mycotoxins in common animal-feed matrices, including DDGS.
Assuntos
Ração Animal/análise , Ração Animal/microbiologia , Micotoxinas/análise , Espectrometria de Massas por Ionização por Electrospray/métodos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Grão Comestível/química , Grão Comestível/microbiologia , Limite de Detecção , Espectrometria de Massas em Tandem/métodosRESUMO
Yeast cell wall-based preparations have shown efficacy against Aspergillus-based toxins but have lower impact against type-B trichothecenes. Presently, we investigated a combination of deoxynivalenol (DON), T-2 toxin (T2) and zearalenone (ZEA), and the effect of a yeast cell wall extract (YCWE) and a post-biotic yeast cell wall-based blend (PYCW) with the objectives of preventing mycotoxins' negative effects in commercial broilers. A total of 720 one-day-old male Cobb broilers were randomly allocated to: (1) control diet, (aflatoxins 6 µg/kg; cyclopiazonic acid 15 µg/kg; fusaric acid 25 µg/kg; fumonisin B1 310 µg/kg); (2) Diet1 + 0.2% YCWE; (3) Diet1 + 0.2% PYCW; (4) Contaminated diet (3.0 mg/kg DON; 2.17 mg/kg 3-acetyldeoxynivalenol; 104 g/kg T2; 79 g/kg ZEA); (5) Diet4 + 0.2% YCWE; and (6) Diet4 + 0.2% PYCW. Naturally contaminated diets adversely affected performance, serum biochemistry, liver function, immune response, altered cecal SCFA goblet cell count and architecture of intestinal villi. These adverse effects were reduced in birds fed PYCW and to a lesser extent YCWE, indicating protection against toxic assault. PYCW yielded better production performance and stimulated liver function, with higher response to NDV and IBV vaccination. Furthermore, mycotoxins were found to affect production outputs when evaluated with the European poultry production efficiency factor compared to control or YCWE and PYCW supplemented treatments. Taken together, YCWE, when complemented with nutritional add-ons (PYCW), could potentiate the remediation of the negative effects from a multi mycotoxins dietary challenge in broiler birds.
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Micotoxinas , Zearalenona , Animais , Parede Celular , Galinhas , Masculino , Micotoxinas/toxicidade , Extratos Vegetais , Saccharomyces cerevisiaeRESUMO
[This corrects the article DOI: 10.1021/acsomega.1c02158.].
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Frequent detection of mycotoxins ochratoxin A (OTA) and citrinin (CIT) in ruminant feed and feedstuff can be a potential threat to feed safety, animal performance and health. Ineffective biodegradation of these mycotoxins by rumen microflora following ingestion of contaminated feeds can lead to their circulatory transport to tissues such as mammary gland as the result of their biodistribution throughout the body. The bovine mammary epithelium plays a pivotal role in maintaining milk yield and composition and contributes to innate immune defense of the udder. The present study is the first to investigate individual effects of OTA and CIT on barrier and innate immune functions of the bovine mammary epithelium using a bovine mammary epithelial cell line (MAC-T). Results indicated that OTA and CIT exposure for 48 h significantly decreased cell viability in a concentration-dependent manner (p < 0.05). A decrease in transepithelial electrical resistance and increase in paracellular flux of FITC-40 kDa dextran was significantly induced by OTA treatment (p < 0.05), but not by CIT after 48 h exposure. qPCR was performed for assessment of expression of tight-junction proteins, Toll-like receptor 4 (TLR4) and cytokines after 4, 24 and 48 h of exposure. Both OTA and CIT markedly downregulated expression of claudin 3 and occludin (p < 0.05), whereas CIT did not affect zonula occludens-1 expression. Expression of TLR4 was significantly upregulated by OTA (p < 0.001) but downregulated by CIT (p < 0.05) at 48 h. Expression of IL-6, TNF-a and TGF-ß was significantly upregulated by OTA (p < 0.05), whereas IL-6 and TGF-ß expression was downregulated by CIT (p < 0.01). These results suggest that OTA and CIT could potentially differentially modulate barrier and innate immune functions of mammary epithelium. The present study not only throws light on the individual toxicity of each mycotoxin on bovine mammary epithelium but also lays the foundation for future studies on the combined effects of the two mycotoxins.
Assuntos
Citrinina , Ocratoxinas , Animais , Bovinos , Citrinina/toxicidade , Claudina-3 , Dextranos , Células Epiteliais , Fluoresceína-5-Isotiocianato/análogos & derivados , Imunidade , Interleucina-6 , Ocludina , Ocratoxinas/toxicidade , Permeabilidade , Distribuição Tecidual , Receptor 4 Toll-Like , Fator de Crescimento Transformador betaRESUMO
The effect of mycotoxins (MT) on broiler performance without or with the inclusion of yeast cell wall extract (YCWE, Mycosorb, Alltech, Inc., KY) was evaluated in a random-effects meta-analysis. Data was extracted from 25 research experiments with a total of 10,307 broilers. Broilers fed MT had lower (P < 0.001) body weight gain (BWG, -217 g), reduced feed intake (FI, -264 g), increased feed conversion ratio (FCR, 0.12), and greater mortality by 2.01%. Inclusion of YCWE improved (P < 0.001) BWG (59 g) and FI (65 g), lowered FCR (-0.05), and reduced mortality by 1.74%. Additionally, change in European Production Efficiency Factor (EPEF) was assessed. Feeding MT lowered (P < 0.001) EPEF while YCWE increased (P < 0.001) EPEF. Finally, the carbon footprint of production was evaluated. Control fed birds produced an estimated 1.93 kg CO2-equivalent/kg liveweight (LW), while MT fed broilers produced 2.13 kg CO2-equivalent/kg LW and YCWE inclusion lowered this to 2.03 kg CO2-equivalent/kg LW which resulted in -25 tonnes less CO2-equivalent output per 100,000 birds with YCWE. In conclusion, mycotoxins can play a role in reducing broiler performance and farm production output, as well as increase the carbon footprint. Inclusion of YCWE in feed under a mycotoxin challenge can improve broiler performance and output, as well as lower carbon footprint, which could play a role in farm efficiency, profitability, and environmental sustainability.
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Micotoxinas , Ração Animal/análise , Animais , Dióxido de Carbono/análise , Parede Celular/química , Galinhas , Dieta/veterinária , Suplementos Nutricionais/análise , Extratos Vegetais , Saccharomyces cerevisiaeRESUMO
Mycotoxins are toxic secondary metabolites produced by filamentous fungi that are commonly detected as natural contaminants in agricultural commodities worldwide. Mycotoxin exposure can lead to mycotoxicosis in both animals and humans when found in animal feeds and food products, and at lower concentrations can affect animal performance by disrupting nutrient digestion, absorption, metabolism, and animal physiology. Thus, mycotoxin contamination of animal feeds represents a significant issue to the livestock industry and is a health threat to food animals. Since prevention of mycotoxin formation is difficult to undertake to avoid contamination, mitigation strategies are needed. This review explores how the mycotoxins aflatoxins, deoxynivalenol, zearalenone, fumonisins and ochratoxin A impose nutritional and metabolic effects on food animals and summarizes mitigation strategies to reduce the risk of mycotoxicity.
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The detrimental footprint of mycotoxins in agriculture and on animal production has been widely recognized, especially in swine. Despite an increased number of research evaluating the toxicokinetics of mycotoxins in animal organisms, the absorption, distribution, metabolization, and excretion (ADME) patterns of zearalenone (ZEN) need further understanding. Furthermore, in vivo bioindicator for ZEN exposure in individual pigs has yet to be characterized. This study explored the ADME of ZEN in Bama Aroma pigs, a Chinese miniature pig breed, that has been used herein as a swine model. The findings revealed that ZEN was mainly metabolized into α-zearalenol (α-ZOL), and both ZEN and α-ZOL were mostly found in conjugated forms in the plasma, urine, and bile. The concentration and composition patterns of ZEN and its metabolites were tissue-specific, implying that the small intestine, liver, kidney, and lung play different roles in ZEN metabolism. The plasma concentrations of ZEN + α-ZOL highly correlated (R2 = 0.993) with the ZEN dietary exposure and may be utilized as a bioindicator to investigate animal exposure and mitigation efficacy of mycotoxin detoxifiers. This research would provide both fundamental information and a useful animal model for ZEN toxicity and detoxification studies.
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Micotoxinas , Zearalenona , Animais , Suínos , Zearalenona/metabolismo , Porco Miniatura/metabolismo , Biomarcadores Ambientais , Micotoxinas/metabolismoRESUMO
Mycotoxins contaminate crops worldwide and play a role in animal health and performance. Multiple mycotoxins may co-occur which may increase the impact on the animal. To assess the multiple mycotoxin profile of corn (Zea mays), we conducted a 7-year survey of new crop corn grain and silage in the United States. A total of 711 grain and 1117 silage samples were collected between 2013 and 2019 and analyzed for the simultaneous presence of 35 mycotoxins using ultra-performance liquid chromatography-tandem mass spectrometry. The measured mean number of mycotoxins per sample were 4.8 (grain) and 5.2 (silage), ranging from 0 to 13. Fusaric acid (FA) was most frequently detected in 78.1 and 93.8% of grains and silages, respectively, followed by deoxynivalenol (DON) in 75.7 and 88.2% of samples. Fumonisin B1 (FB1), fumonisin B2 and 15-acetyl-deoxynivalenol (15ADON) followed. The greatest (p < 0.05) co-occurrence was between FA and DON in 59.1% of grains and 82.7% of silages, followed by FA with FB1, DON with 15ADON, and FA with 15ADON. Although many samples had lower mycotoxin concentrations, 1.6% (grain) and 7.9% (silage) of tested samples had DON ≥ 5000 µg/kg. Fumonisins were detected ≥ 10,000 µg/kg in 9.6 and 3.9% of grain and silage samples, respectively. Concentrations in grain varied by year for eight mycotoxin groups (p < 0.05), while all 10 groups showed yearly variations in silage. Our survey suggest that multiple mycotoxins frequently co-occur in corn grain and silage in the United States, and some of the more prevalent mycotoxins are those that may not be routinely analyzed (i.e., FA and 15ADON). Assessment of multiple mycotoxins should be considered when developing management programs.
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Grão Comestível/química , Contaminação de Alimentos/análise , Micotoxinas/análise , Silagem/análise , Zea mays/química , Estados UnidosRESUMO
Alkaloid toxicities negatively impact livestock health and production. To assess alkaloid occurrences, adsorbent technologies may offer effective means to their extraction and isolation from a complex feed matrix. In this study, molecularly imprinted polymers (MIPs) were synthesized and evaluated for their specificity of binding to various ergot alkaloids. Co-polymers of styrene and hydroxyethyl methacrylate were synthesized in the absence or presence of an ergotamine (ETA) template, yielding non-imprinted polymer (NIP) and molecularly imprinted polymer (MIP), respectively. The influence of parameters such as pH, temperature, and initial concentration on the adsorption of ergot alkaloids was evaluated along with their application as solid phase extraction materials. Chemical and morphological properties were characterized. Adsorption was generally greater for MIP compared to NIP. Cross-reactivity with related alkaloids existed due to similarities in structure and functional groups and was dependent on the type and concentration of alkaloid and polymer type (alkaloid type × concentration × product; P < 0.05). The pH of the medium had no influence on the binding properties of polymers toward ETA within a pH range of 2-10. Binding was independent of temperature between 36 and 42 °C. When kinetics of adsorption were evaluated, the Langmuir isotherm had a better fit (R 2 > 0.95) to adsorption equilibrium data than the Freundlich equation. The maximum amounts adsorbed (Q o) from the Langmuir model were 8.68 and 7.55 µM/g for MIP and NIP, respectively. Fourier transform infrared, scanning and tandem electron microscopy, and Brunauer-Emmett-Teller analysis confirmed a highly porous MIP structure with a greater surface area compared to NIP. Binding characteristics evaluated with computational strategy using molecular docking experiments and in vitro in a complex media (rumen fluid) indicated a stronger ETA adsorption by the tested composition selected among other polymeric materials and affinity of MIP compared with NIP. This study suggested the possible utility of MIP as a solid phase extraction sorbent for applications in analytical chemistry or sensing devices tailored to track ergot alkaloid incidence and the fate of those alkaloids in complex ruminal digestive samples.
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Mycotoxins are naturally occurring toxins that can affect livestock health and performance upon consumption of contaminated feedstuffs. To mitigate the negative effects of mycotoxins, sequestering agents, adsorbents, or binders can be included to feed to interact with toxins, aiding their passage through the gastrointestinal tract (GI) and reducing their bioavailability. The parietal cell wall components of Saccharomyces cerevisiae have been found to interact in vitro with mycotoxins, such as, but not limited to, aflatoxin B1 (AFB1), and to improve animal performance when added to contaminated diets in vivo. The present study aimed to examine the pharmacokinetics of the absorption of radiolabeled AFB1 in rats in the presence of a yeast cell wall-based adsorbent (YCW) compared with that in the presence of the clay-based binder hydrated sodium calcium aluminosilicate (HSCAS). The results of the initial pharmacokinetic analysis showed that the absorption process across the GI tract was relatively slow, occurring over a matter of hours rather than minutes. The inclusion of mycotoxin binders increased the recovery of radiolabeled AFB1 in the small intestine, cecum, and colon at 5 and 10 h, revealing that they prevented AFB1 absorption compared with a control diet. Additionally, the accumulation of radiolabeled AFB1 was more significant in the blood plasma, kidney, and liver of animals fed the control diet, again showing the ability of the binders to reduce the assimilation of AFB1 into the body. The results showed the potential of YCW in reducing the absorption of AFB1 in vivo, and in protecting against the damaging effects of AFB1 contamination.
Assuntos
Aflatoxina B1/farmacocinética , Silicatos de Alumínio/farmacologia , Parede Celular/metabolismo , Colo/efeitos dos fármacos , Suplementos Nutricionais , Absorção Intestinal/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo , Administração Oral , Adsorção , Aflatoxina B1/administração & dosagem , Aflatoxina B1/toxicidade , Animais , Colo/metabolismo , Intestino Delgado/metabolismo , Ratos Sprague-Dawley , Distribuição TecidualRESUMO
BACKGROUND: Docosahexaenoic acid (DHA) plays an important role in brain and retinal development in dogs. However, supranutritional dietary supplementation can result in health issues, including gastrointestinal bleeding, making the accurate analysis of DHA in dog food important for nutritional and welfare regulatory compliance. OBJECTIVE: The aim of this study was to conduct a validation and verification of the AOAC 996.06 method, and hence establish its fitness for purpose, for the analysis of DHA in dried dog food supplemented with a heterotrophically grown unextracted DHA-rich Aurantiochytrium limacinum biomass. METHODS: The AOAC 996.06 method, which involves the use of gas chromatography coupled to flame ionization detection (GC-FID), was used to conduct a validation of the analysis of DHA in dried dog food and the results were verified in a second laboratory. RESULTS: The method was found to be linear over the ranges analyzed and results were found to be within the acceptance criteria for precision and accuracy, verifying the applicability for this matrix. The selectivity and sensitivity of the method were also determined. CONCLUSIONS: The AOAC 996.06 method is fit for purpose for the analysis of DHA in dry dog food kibble. HIGHLIGHTS: The method can be applied to various dog food samples, supplemented with an unextracted Aurantiochytrium limacinum biomass, using alternative manufacturing methods, i.e. pelleted and extruded with no significant matrix effects being observed.