RESUMEN
BACKGROUND: Naturally occurring aflatoxins may contribute to poor growth and nutritional statuses in children. OBJECTIVES: We analyzed the relationship between contemporary and lagged aflatoxin exposure and 1) length-for-age z-score (LAZ); and 2) length, knee-heel length, stunting, weight-for-age z-score (WAZ), and weight-for-length z-score (WLZ). METHODS: We conducted a longitudinal birth cohort study involving 1675 mother-infant dyads in rural Nepal. Participants were repeatedly visited from pregnancy to 2 years of age (2015-2019). One blood sample was collected during pregnancy and 4 samples were collected from the children at 3, 6, 12, and 18-22 months of age to measure concentrations of aflatoxin B1 (AFB1)-lysine adduct. Multivariate linear fixed-effects and logistic models with generalized estimating equations were used to identify associations between child growth and aflatoxin exposure. RESULTS: AFB1-lysine adducts were detected in the majority of children (at 3 months, 80.5%; at 6 months, 75.3%; at 12 months, 81.1%; and at 18-22 months, 85.1%) and in 94.3% of pregnant women. Changes in contemporary ln child AFB1-lysine adduct concentrations were significantly associated with changes in LAZ (ß, -0.05; 95% CI, -0.09 to -0.02; P = 0.003), length (ß, -0.19; 95% CI, -0.29 to -0.10; P < 0.001), knee-heel length (ß, -0.09; 95% CI, -0.13 to -0.05; P < 0.001), and WAZ (ß, -0.04; 95% CI, -0.07 to -0.005; P = 0.022). Serum aflatoxin concentrations were associated with stunting (OR, 1.18; 95% CI, 1.05-1.32; P = 0.005). Similar results were found in the models using changes in contemporary ln AFB1 adjusted for changes in child weight, with significant associations with changes in WLZ (ß, -0.07; 95% CI, -0.10 to -0.03; P < 0.001). Changes in time-lagged ln AFB1 (unadjusted and adjusted for changes in child weight) were associated with changes in length and knee-heel length. CONCLUSIONS: Our results add to the growing body of evidence confirming chronic aflatoxin exposure and suggest that exposure is significantly correlated with various negative growth outcomes, which may vary by child weight status. This trial was registered at clinicaltrials.gov as NCT03312049.
Asunto(s)
Aflatoxinas/administración & dosificación , Aflatoxinas/toxicidad , Desarrollo Óseo/efectos de los fármacos , Fenómenos Fisiológicos Nutricionales Infantiles , Exposición a Riesgos Ambientales , Adolescente , Adulto , Desarrollo Óseo/fisiología , Niño , Desarrollo Infantil , Preescolar , Estudios de Cohortes , Femenino , Trastornos del Crecimiento , Humanos , Lactante , Masculino , Persona de Mediana Edad , Nepal , Embarazo , Adulto JovenRESUMEN
Human biomonitoring is an important tool to assess human exposure to chemicals, contributing to describe trends of exposure over time and to identify population groups that could be under risk. Aflatoxins are genotoxic and carcinogenic food contaminants causing hepatocellular carcinoma, the third leading cause of cancer deaths worldwide. In Portugal, scarce data are available regarding exposure to aflatoxins and no previous study used human biomonitoring data to comprehensively characterize the associated burden of disease. 24 h urine and first-morning urine paired samples were collected by 94 participants and were analyzed by liquid chromatography-tandem mass spectrometry for the quantitative determination of aflatoxins (B1, B2, G1, G2 and M1). Deterministic and probabilistic models were developed to assess the Portuguese exposure to aflatoxins and to estimate the health impact of this exposure, estimating the attributed Disability-Adjusted Life Years (DALYs). Aflatoxins were detected in a maximum of 13% (AFB1), 16% (AFB2), 1% (AFG1), 2% (AFG2) and 19% (AFM1) of the urine samples. Data obtained through the probabilistic approach revealed an estimated mean probable daily intake of 13.43 ng/kg body weight per day resulting in 0.13 extra cases of hepatocellular carcinoma, corresponding to mean annual DALYs of 172.8 for the Portuguese population (10291027 inhabitants). The present study generated for the first time and within a human biomonitoring study, reliable and crucial data to characterize the burden associated to the exposure to aflatoxins of the Portuguese population. The obtained results constitute an imperative support to risk managers in the establishment of preventive policy measures that contribute to ensure public health protection.
Asunto(s)
Aflatoxinas/administración & dosificación , Aflatoxinas/toxicidad , Adulto , Aflatoxinas/orina , Biomarcadores/orina , Dieta , Femenino , Contaminación de Alimentos , Humanos , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Portugal , Adulto JovenRESUMEN
Vitamins play an essential role in broiler nutrition. They are fundamental for normal metabolic and physiological process, and their requirements for poultry are not fixed and can be affected by multiple factors. In contrast, mycotoxins are a challenging issue because they hinder performance and the immune system. Vitamin supplementation above minimum requirements would permit improvement in productive potential, health, bone and meat quality in a situation of mycotoxin challenge. The objective of this study was to determine the influence of optimum vitamin nutrition in diets contaminated with aflatoxin in broilers from 1 to 44 days of age. A total of 1800 Cobb 500 male chicks were randomized to 15 sets of eight treatment groups, each containing 15 birds using a 2 × 2 × 2 factorial design (commercial vitamin levels and high vitamin levels, two levels of aflatoxin - 0 and 0.5 ppm with binder levels of 0 and 10 000 mg/kg). The mash diets were corn and soybean meal based, formulated according to commercial practices. Feed intake, weight gain and feed conversion were analyzed for birds from 1 to 44 days of age. To determine carcass characteristics (carcass yield, breast yield and leg yield) and black bone syndrome, two birds were slaughtered from each group at 45 days. Other analyses included breast tenderness, water loss by dripping and malonaldehyde concentrations. The results demonstrated that broilers that were fed high levels of vitamins showed better weight gain, feed conversion, carcass yield and breast yield than broilers that were fed diets with commercial vitamin levels (P < 0.05); also, broilers that were fed diets containing 0.5 ppm aflatoxin had lower weight gain, carcass yield and breast yield (P < 0.05). The use of 10 000 mg/kg of binder improved (P < 0.05) feed conversion throughout the rearing period. We conclude that aflatoxin negatively affects performance and carcass yield; however, feeding optimum vitamin nutrition improved these performance traits.
Asunto(s)
Aflatoxinas/efectos adversos , Enfermedades Óseas/veterinaria , Pollos , Carne/análisis , Enfermedades de las Aves de Corral/epidemiología , Vitaminas/metabolismo , Aflatoxinas/administración & dosificación , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Enfermedades Óseas/epidemiología , Enfermedades Óseas/etiología , Brasil/epidemiología , Pollos/crecimiento & desarrollo , Pollos/fisiología , Dieta/veterinaria , Suplementos Dietéticos/análisis , Masculino , Enfermedades de las Aves de Corral/etiología , Distribución Aleatoria , Vitaminas/administración & dosificaciónRESUMEN
Dietary exposure to aflatoxin B1 (AFB1) is a significant contributor to the incidence of hepatocellular carcinomas globally. AFB1 exposure leads to the formation of AFB1-N7-guanine (AFB1-N7-Gua) and two diastereomers of the imidazole ring-opened 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydroxyaflatoxin B1 (AFB1-FapyGua) in DNA. These adducts lead to G â T transversion mutations with the ring-opened adduct being more mutagenic than the cationic species. Accurate measurement of these three adducts as biomarkers in DNA and urine will help identify dietary exposure to AFB1 as a risk factor in the development of hepatocellular carcinoma worldwide. Herein, we report an improved methodology for the measurement of AFB1-N7-Gua and the two diastereomers of AFB1-FapyGua using liquid chromatography-tandem mass spectrometry with isotope dilution. We measured the levels of these compounds in liver DNA of six control mice and six AFB1-treated mice. Levels varying from 1.5 to 45 lesions/106 DNA bases in AFB1-treated mice were detected depending on the compound and animal. No background levels of these adducts were detected in control mice. We also tested whether the AFB1 treatment caused oxidatively induced DNA base damage using gas chromatography-tandem mass spectrometry with isotope dilution. Although background levels of several pyrimidine- and purine-derived lesions were detected, no increases in these levels were found upon AFB1 treatment of mice. On the other hand, significantly increased levels of (5' R)- and (5' S)-8,5'-cyclo-2'-deoxyadenosines were observed in liver DNA of AFB1-treated mice. The impact of this work is expected to achieve the accurate measurement of three AFB1-DNA adducts and oxidatively induced DNA lesions as biomarkers of AFB1 exposure as germane to investigations designed for the prevention of aflatoxin-related hepatocellular carcinomas and for determining the effects of genetic deficiencies in human populations.
Asunto(s)
Aflatoxinas/química , Aflatoxinas/farmacología , Aductos de ADN/química , Daño del ADN , Guanina/química , Técnica de Dilución de Radioisótopos , Aflatoxinas/administración & dosificación , Animales , Cromatografía Liquida , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Conformación Molecular , Oxidación-ReducciónRESUMEN
Creatine kinase (CK) activity, through the creatine-kinase-phosphocreatine (CK/PCr) system, provides a temporal and spatial energy buffer to maintain cellular energetic homeostasis, being responsible to provide adenosine triphosphate (ATP) to the proper function of ATPases enzymes, such as the sodium-potassium (Na+, K+-ATPase) and hydrogen (H+-ATPase) pumps. Thus, the aim of this study was to evaluate the involvement of CK/PCr system in the impairment of energetic homeostasis in piglets fed with a diet co-contaminated with mycotoxins, as well as the effects on ATPases enzymes. Animals were randomly divided in two groups (eight repetitions with two animals each): CON (basal diet) and MYC (mycotoxin diet; 9300⯵g/kg of aflatoxins and 8000⯵g/kg of fumonisins) which were feed during 15 days. Piglets that received a diet containing 300⯵g/kg of aflatoxins and 8000⯵g/kg of fumonisins (MYC group) presented lower body weight on days 10 and 15 of experiment when compared to control (CON group). Serum CK activity was lower on days 5, 10 and 15 of experiment in the MYC group. The same occurred for serum Na+, K+-ATPase and H+-ATPase activities on days 10 and 15 when compared to CON group. Moreover, serum calcium levels were superior on day 15 of experiment in the MYC group, while serum potassium and sodium levels were lower in comparison to CON group. Based on these evidences, a diet co-contaminated by aflatoxins and fumonisins inhibits serum CK activity, impairing the energetic homeostasis. This inhibition alters the activities of ATPases (Na+, K+-ATPase and H+-ATPase), contributing to the imbalance of Na+, K+ and Ca+ ionic levels. In summary, the cascade of alterations contributes directly to disease pathogenesis of piglets intoxicated by mycotoxins.
Asunto(s)
Adenosina Trifosfatasas/sangre , Creatina Quinasa/sangre , Dieta/veterinaria , Contaminación de Alimentos , Micotoxinas/administración & dosificación , Aflatoxinas/administración & dosificación , Aflatoxinas/toxicidad , Animales , Animales Recién Nacidos , Peso Corporal , Calcio/sangre , Fumonisinas/administración & dosificación , Fumonisinas/toxicidad , Micotoxinas/toxicidad , Potasio/sangre , Sodio/sangre , PorcinosRESUMEN
Climate change has been indicated as a driver for food safety issues worldwide, mainly due to the impact on the occurrence of food safety hazards at various stages of food chain. Mycotoxins, natural contaminants produced by fungi, are among the most important of such hazards. Aflatoxins, which have the highest acute and chronic toxicity of all mycotoxins, assume particular importance. A recent study predicted aflatoxin contamination in maize and wheat crops in Europe within the next 100 years and aflatoxin B1 is predicted to become a food safety issue in Europe, especially in the most probable scenario of climate change (+2°C). This review discusses the potential influence of climate change on the health risk associated to aflatoxins dietary exposure of Portuguese population. We estimated the burden of disease associated to the current aflatoxin exposure for Portuguese population in terms of Disability Adjusted Life Years (DALYs). It is expected that in the future the number of DALYs and the associated cases of hepatocellular carcinoma due to aflatoxins exposure will increase due to climate change. The topics highlighted through this review, including the potential impact on health of the Portuguese population through the dietary exposure to aflatoxins, should represent an alert for the potential consequences of an incompletely explored perspective of climate change. Politics and decision-makers should be involved and committed to implement effective measures to deal with climate change issues and to reduce its possible consequences. This review constitutes a contribution for the prioritisation of strategies to face the unequal burden of effects of weather-related hazards in Portugal and across Europe.
Asunto(s)
Aflatoxinas/análisis , Cambio Climático , Exposición Dietética/análisis , Contaminación de Alimentos/análisis , Inocuidad de los Alimentos , Evaluación del Impacto en la Salud , Micotoxinas/análisis , Aflatoxinas/administración & dosificación , Aflatoxinas/efectos adversos , Exposición Dietética/efectos adversos , Monitoreo del Ambiente , Humanos , Micotoxinas/administración & dosificación , Micotoxinas/efectos adversos , PortugalRESUMEN
We aimed to determine whether aflatoxin dietary exposure plays a role in the high incidence of hepatocellular carcinoma (HCC) observed among Hispanics in South Texas. We measured TP53R249S somatic mutation, hallmark of aflatoxin etiology in HCC, using droplet digital PCR and RFLP. TP53R249S mutation was detected in 3 of 41 HCC tumors from Hispanics in South Texas (7.3%). We also measured TP53R249S mutation in plasma cell-free DNA (cfDNA) from 218 HCC patients and 96 Hispanic subjects with advanced fibrosis or cirrhosis, from South Texas. The mutation was detected only in Hispanic and Asian HCC patients, and patients harboring TP53R249S mutation were significantly younger and had a shorter overall survival. The mutation was not detected in any Hispanic subject with advanced fibrosis or cirrhosis. Genes involved in cell-cycle control of chromosomal replication and in BRCA1-dependent DNA damage response were enriched in HCCs with TP53R249S mutation. The E2F1 family members, E2F1 and E2F4, were identified as upstream regulators. TP53R249S mutation was detected in 5.7% to 7.3% of Hispanics with HCC in South Texas. This mutation was associated with a younger age and worse prognosis. TP53R249S was however not detected in Hispanics in South Texas with cirrhosis or advanced fibrosis. Aflatoxin exposure may contribute to a small number of HCCs in Hispanics in South Texas, but the detection of TP53R249S mutation in plasma cfDNA is not a promising biomarker of risk assessment for HCC in subjects with cirrhosis or advanced fibrosis in this population. Cancer Prev Res; 11(2); 103-12. ©2017 AACR.
Asunto(s)
Aflatoxinas/administración & dosificación , Carcinoma Hepatocelular/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Hispánicos o Latinos/genética , Neoplasias Hepáticas/genética , Mutación , Proteína p53 Supresora de Tumor/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/patología , Ácidos Nucleicos Libres de Células , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Venenos/administración & dosificación , Prevalencia , Pronóstico , Texas/epidemiologíaRESUMEN
Aflatoxin exposure is an important public health concern in sub-Saharan Africa as well as parts of Latin America and Asia. In addition to hepatocellular carcinoma, chronic aflatoxin exposure is believed to play a role in childhood growth impairment. The most reliable biomarker of chronic aflatoxin exposure is the aflatoxin-albumin adduct, as measured by ELISA or isotope dilution mass spectrometry (IDMS). In this report, we have used high resolution LC-MS/MS with IDMS to quantitate AFB1-lysine in an extremely vulnerable population of Nigerian children suffering from severe acute malnutrition. To increase the sensitivity and reliability of the analyses, a labelled AFB1-13C615N2-lysine internal standard was synthesized. AFB1-lysine concentrations in this population ranged between 0.2 and 59.2 pg/mg albumin, with a median value of 2.6 pg/mg albumin. AFB1-lysine concentrations were significantly higher in stunted children (median = 4.6 pg/mg) compared to non-stunted (1.2 pg/mg), as well as in children with severe acute malnutrition (4.3 pg/mg) compared to controls (0.8 pg/mg). The median concentrations were also higher in children with kwashiorkor (6.3 pg/mg) compared to those suffering from marasmus (0.9 pg/mg). This is the first report of the use of high-resolution mass spectrometry to quantitate AFB1-lysine in humans.
Asunto(s)
Aflatoxinas/toxicidad , Trastornos de la Nutrición del Niño/complicaciones , Trastornos de la Nutrición del Niño/epidemiología , Aflatoxinas/administración & dosificación , Aflatoxinas/química , Trastornos de la Nutrición del Niño/sangre , Preescolar , Humanos , Lactante , Estructura Molecular , NigeriaRESUMEN
Producing aflatoxin-detoxifizyme (ADTZ) in pigs to control the AFT contamination of pig feed is a new research strategy by transgenic technology. In this study, transgenic pigs specifically expressing ADTZ gene in the parotid gland were successfully produced by somatic cell nuclear transfer technology. The ADTZ activity in saliva of 6 transgenic pigs was found to be 7.11 ± 2.63 U/mL. The feeding trial with aflatoxin (AFT) results showed that there were significant difference about the serum biochemical index such as total protein (TP), albumin (ALB), globulin (GLB) contents and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity and AFT residues in serum and liver between the pigs in the test treatment (transgenic pigs) producing ADTZ and those in the positive control (P < 0.05). In order to investigate the inheritance of the transgene, 11 G1 transgenic pigs were successfully obtained. The ADTZ activity in saliva of 11 G1 transgenic pigs was found to be 5.82 ± 1.53 U/mL. The feeding trial with AFT results showed that the serum biochemical index containing TP, ALB and GLB contents and ALT and AST activity and AFB1 residues in serum and liver of the pigs in the test treatment (transgenic pigs) producing ADTZ were significantly different than those in the positive control (P < 0.05). The above results demonstrated that ADTZ produced in transgenic pigs could improve the effect of the AFT contamination of feed on pigs.
Asunto(s)
Animales Modificados Genéticamente/genética , Hígado/metabolismo , Complejos Multienzimáticos/genética , Glándula Parótida/metabolismo , Aflatoxinas/administración & dosificación , Animales , Proteínas Sanguíneas/genética , Hígado/efectos de los fármacos , Complejos Multienzimáticos/biosíntesis , Saliva/efectos de los fármacos , Saliva/metabolismo , Albúmina Sérica/genética , Porcinos/genéticaRESUMEN
Bacillus subtilis ANSB060 isolated from fish gut is very effective in detoxifying aflatoxins in feed and feed ingredients. The purpose of this research was to investigate the effects of B. subtilis ANSB060 on growth performance, body antioxidant functions, and aflatoxin residues in ducks fed moldy maize naturally contaminated with aflatoxins. A total of 1500 18-d-old male Cherry Valley ducks with similar body weight were randomly assigned to five treatments with six replicates of 50 ducks per repeat. The experiment design consisted of five dietary treatments labeled as C0 (basal diet containing 60% normal maize), M0 (basal diet containing 60% moldy maize contaminated with aflatoxins substituted for normal maize), M500, M1000, and M2000 (M0 +500, 1000 or 2000 g/t aflatoxin biodegradation preparation mainly consisted of B. subtilis ANSB060). The results showed that ducks fed 22.44 ± 2.46 µg/kg of AFB1 (M0) exhibited a decreasing tendency in average daily gain (ADG) and total superoxide dismutase (T-SOD) activity in serum, and T-SOD and glutathione peroxidase (GSH-Px) activities in the liver significantly decreased along with the appearance of AFB1 and AFM1 compared with those in Group C0. The supplementation of B. subtilis ANSB060 into aflatoxin-contaminated diets increased the ADG of ducks (p > 0.05), significantly improved antioxidant enzyme activities, and reduced aflatoxin accumulation in duck liver. In conclusion, Bacillus subtilis ANSB060 in diets showed an ameliorating effect to duck aflatoxicosis and may be a promising feed additive.
Asunto(s)
Aflatoxinas/análisis , Alimentación Animal/análisis , Bacillus subtilis , Dieta/veterinaria , Contaminación de Alimentos/prevención & control , Aflatoxinas/administración & dosificación , Animales , Patos/crecimiento & desarrollo , Patos/microbiología , Contaminación de Alimentos/análisis , Microbiología de Alimentos , Enfermedades Transmitidas por los Alimentos/terapia , Enfermedades Transmitidas por los Alimentos/veterinaria , Glutatión Peroxidasa/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Malondialdehído/metabolismo , Distribución Aleatoria , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Zea mays/química , Zea mays/microbiologíaRESUMEN
Infants less than 6 months of age receiving foods other than breast milk are at a high risk of exposure to mycotoxins. We surveyed food intake and estimated the risk of exposures to aflatoxin and fumonisin mycotoxins for infants less than 6 months of age in Northern Tanzania. A total of 143 infants were progressively recruited and three follow-up visits were made at 1, 3 and 5 months of age. A 24-h dietary recall technique was used to estimate flour intake of infants who had been introduced to maize foods. Aflatoxins and fumonisins in the flours were analysed using high-performance liquid chromatography technique. Exposure to aflatoxins or fumonisins was estimated using the deterministic approach. By the age of 3 months, 98 infants had started taking food; 67 of them, maize flours at levels ranging from 0.57 to 37.50 g per infant per day (average 8 g per infant per day). Fifty-eight per cent of 67 maize flour samples contained detectable aflatoxins (range 0.33-69.47 µg kg(-1) ; median 6 µg kg(-1) ) and 31% contained detectable fumonisins (range 48-1224 µg kg(-1) ; median 124 µg kg(-1) ). For infants who consumed contaminated flours, aflatoxin exposure ranged from 0.14 to 120 ng kg(-1) body weight (BW) per day (all above the health concern level of 0.017 ng kg(-1) BW per day as recommended by the European Food Safety Agency) and fumonisin exposure ranged from 0.005 to 0.88 µg kg(-1) BW per day. Insignificant association was observed between exposure to fumonisins or aflatoxins and stunting or underweight. Reducing aflatoxin and fumonisin contamination of maize and dietary diversification can prevent infants and the public, in general, from exposure to the toxins.
Asunto(s)
Aflatoxinas/administración & dosificación , Dieta , Contaminación de Alimentos/análisis , Fumonisinas/administración & dosificación , Peso Corporal , Cromatografía Líquida de Alta Presión , Harina/microbiología , Estudios de Seguimiento , Análisis de los Alimentos , Microbiología de Alimentos , Humanos , Lactante , Fenómenos Fisiológicos Nutricionales del Lactante , Factores de Riesgo , Tanzanía , Zea mays/química , Zea mays/microbiologíaRESUMEN
The association between aflatoxin intake from maize-based weaning food and aflatoxin albumin adducts (AF-alb) was investigated in 148 Tanzanian children aged between 12 and 22 months, at 2 visits 6 months apart. At the first visit (storage season) there was a significant correlation at the individual level between AF-alb (geometric mean 43.2 pg/mg albumin) and aflatoxin intake (geometric mean 81.7 ng/kg b.w./d) through maize-based weaning food (r = 0.51, p < 0.01). Overall, this correlation was r = 0.43 (p < 0.01). The AF-alb level in weaning-age children in Tanzania closely reflects aflatoxin intake from maize in weaning food. Exposure levels suggest children may be at risk from aflatoxin associated health effects.
Asunto(s)
Aflatoxinas/administración & dosificación , Biomarcadores/sangre , Contaminación de Alimentos/análisis , Aflatoxinas/sangre , Albúminas , Ingestión de Alimentos , Femenino , Contaminación de Alimentos/prevención & control , Humanos , Lactante , Modelos Lineales , Masculino , Análisis Multivariante , Tanzanía , Destete , Zea maysRESUMEN
Current methods for cancer risk assessment result in single values, without any quantitative information on the uncertainties in these values. Therefore, single risk values could easily be overinterpreted. In this study, we discuss a full probabilistic cancer risk assessment approach in which all the generally recognized uncertainties in both exposure and hazard assessment are quantitatively characterized and probabilistically evaluated, resulting in a confidence interval for the final risk estimate. The methodology is applied to three example chemicals (aflatoxin, N-nitrosodimethylamine, and methyleugenol). These examples illustrate that the uncertainty in a cancer risk estimate may be huge, making single value estimates of cancer risk meaningless. Further, a risk based on linear extrapolation tends to be lower than the upper 95% confidence limit of a probabilistic risk estimate, and in that sense it is not conservative. Our conceptual analysis showed that there are two possible basic approaches for cancer risk assessment, depending on the interpretation of the dose-incidence data measured in animals. However, it remains unclear which of the two interpretations is the more adequate one, adding an additional uncertainty to the already huge confidence intervals for cancer risk estimates.
Asunto(s)
Neoplasias/inducido químicamente , Medición de Riesgo/métodos , Aflatoxinas/administración & dosificación , Aflatoxinas/toxicidad , Animales , Carcinógenos/administración & dosificación , Carcinógenos/toxicidad , Dimetilnitrosamina/administración & dosificación , Dimetilnitrosamina/toxicidad , Relación Dosis-Respuesta a Droga , Eugenol/administración & dosificación , Eugenol/análogos & derivados , Eugenol/toxicidad , Femenino , Contaminación de Alimentos/análisis , Humanos , Incidencia , Masculino , Modelos Estadísticos , Neoplasias/epidemiología , Medición de Riesgo/estadística & datos numéricos , IncertidumbreRESUMEN
This experiment is designed to investigate the positive effects of commercial nanosilver compound on blood parameters in experimental aflatoxicosis in broiler chickens. For this, 270 one-day-old broiler chickens were randomly divided into six treatment groups with three replicates. The experimental groups were group A: chickens fed with basal diet; group B: chickens fed with 3 ppm productive aflatoxin in basal diet; groups of C, D, E and F received Mycoad (2.5 g/kg diet), Mycoad (2.5 g/kg diet) + productive aflatoxin (3 ppm), Nanocid (2500 ppm), and Nanocid (2500 ppm) + productive aflatoxin (3 ppm) in basal diet, respectively. Results revealed that some of the blood parameters such as mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration lymphocytes, neutrophils, basophils, monocytes, and eosinophils percentage were not affected in this experiment; whereas, hemoglobin percentage and white blood cell (WBC) count in all the groups fed with 3 ppm aflatoxin except nanocid + aflatoxin decreased significantly (p < 0.05). There are no significant differences between the groups that received nanocid + aflatoxin and mycoad + aflatoxin in hemoglobin percentage and WBC count parameters. The red blood cell count and hematocrit in chickens received aflatoxin were significantly lower than other groups (p < 0.05). Therefore, this study suggests that nanocid similar as mycoad can be useful in reducing the adverse effects of aflatoxin on blood parameters in chickens affected with aflatoxicosis.
Asunto(s)
Aflatoxinas/toxicidad , Contaminación de Alimentos/prevención & control , Nanopartículas del Metal/administración & dosificación , Enfermedades de las Aves de Corral/microbiología , Plata/administración & dosificación , Aflatoxinas/administración & dosificación , Alimentación Animal/análisis , Animales , Basófilos/efectos de los fármacos , Pollos , Relación Dosis-Respuesta a Droga , Eosinófilos/efectos de los fármacos , Recuento de Eritrocitos , Índices de Eritrocitos/efectos de los fármacos , Índices de Eritrocitos/fisiología , Recuento de Leucocitos , Linfocitos/efectos de los fármacos , Nanopartículas del Metal/química , Monocitos/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Enfermedades de las Aves de Corral/tratamiento farmacológico , Plata/químicaRESUMEN
Aflatoxins (AF) and fumonisins (FU) are a major problem faced by poultry farmers, leading to huge economic losses. This experiment was conducted to determine the effects of AF (1 mg/kg of feed) and FU (25 mg/kg of feed), singly or in combination, on the lipid metabolism in commercial layers and investigate the efficacy of a commercial binder (2 kg/t of feed) on reducing the toxic effects of these mycotoxins. A total of 168 Hisex Brown layer hens, 37 wk of age, were randomized into a 3 × 2 + 1 factorial arrangement (3 diets with no binder containing AF, FU, and AF+FU; 3 diets with binder containing AF, FU, and AF+FU; and a control diet with no mycotoxins and binders), totaling 7 treatments. The hens contaminated with AF showed the characteristic effects of aflatoxicosis, such as a yellow liver, resulting from the accumulation of liver fat, lower values of plasma very low-density lipoprotein and triglycerides, and higher relative weight of the kidneys and liver. Hepatotoxic and nephrotoxic effects of FU were not observed in this study. On the other hand, the FU caused a reduction in small intestine length and an increase in abdominal fat deposition. The glucan-based binder prevented some of the deleterious effects of these mycotoxins, particularly the effects of AF on hepatic lipid metabolism, kidney relative weight, and FU in the small intestine.
Asunto(s)
Aflatoxina B1/toxicidad , Aflatoxinas/toxicidad , Pollos/metabolismo , Fumonisinas/toxicidad , Metabolismo de los Lípidos/efectos de los fármacos , Aflatoxina B1/administración & dosificación , Aflatoxinas/administración & dosificación , Alimentación Animal/análisis , Animales , Peso Corporal , Dieta/veterinaria , Ingestión de Alimentos , Femenino , Contaminación de Alimentos , Fumonisinas/administración & dosificación , Glucanos/química , OviposiciónRESUMEN
Aflatoxin is a widely occurring and harmful mycotoxin produced by strains of Aspergillus spp. growing on vegetable matter. We investigated the concentration of aflatoxin needed to impair normal physiologic responses and induce acute morbidity and mortality in Northern Bobwhites (Colinus virginianus). Ten wild-caught adult bobwhites (five males and five females) from southern Texas were randomly assigned to each treatment group (0, 100, 500, 1,000, and 2,000 parts per billion (ppb) aflatoxin; n=50). We orally administered 100 µL of aflatoxin, derived from Aspergillus flavus, once per week for 4 wk and monitored bird mass, daily feed consumption, liver histology, and blood chemistries. An in vitro white blood cell proliferation test was conducted using spleen tissue to determine the effect of aflatoxin on the immune system. There was no mortality in the control groups, whereas mortalities occurred in all treatment groups except in the 100 ppb aflatoxin treatment. Immunosuppression, reduction in gamma-globulin, glucose, and gamma-glutamyltransferase blood levels, and abnormal liver histology were observed in aflatoxin-exposed quail. Blood chemistry indicated cellular damage to the liver and kidneys. We concluded that short-term, acute doses of aflatoxin as low as 100 ppb can be detrimental to the health of Northern Bobwhites.
Asunto(s)
Aflatoxinas/toxicidad , Enfermedades de las Aves/inducido químicamente , Enfermedades de las Aves/patología , Colinus , Aflatoxinas/administración & dosificación , Animales , Relación Dosis-Respuesta a Droga , Femenino , MasculinoRESUMEN
OBJECTIVES: The purpose this study is to enhance the anti-tumour activity of austocystin D (AD) by AD-loaded liposomes (AD-Ls). METHODS: AD-Ls were prepared by the film dispersion-ultrasonication method and characterized in terms of particle size and zeta potential, encapsulation efficiency and in-vitro drug release. In vivo, the pharmacokinetics, biodistribution and anti-tumour effect were also compared with those of the solution. KEY FINDINGS: The obtained liposomes were a mildly translucent suspension, with a particle size of 71.26 ± 6.43 nm, a polydispersity index of 0.259 ± 0.017 and a zeta potential of -9.9 ± 1.8 mV. Transmission electron microscope examination showed that the liposomes had a spherical shape and a multilayer structure. The encapsulation efficiency ofAD-Ls was 83.74 ± 1.26%. AD was continuously released from liposomes up to 72 h in in-vitro experiments. The growth of HT-29 tumours in animal models was controlled more effectively by AD-LS than by AD solution. Pharmacokinetic study showed that AD-Ls had higher t½ß and mean retention time. Biodistribution results in tumour-bearing mice showed that the AD-LS could target to liver and tumour. CONCLUSIONS: This study indicates that AD-Ls are a potential carrier of AD for the treatment of tumours in the liver, increasing the cure efficiency and decreasing the side effects on other tissues.
Asunto(s)
Aflatoxinas/administración & dosificación , Antineoplásicos/administración & dosificación , Liposomas/administración & dosificación , Aflatoxinas/química , Aflatoxinas/farmacocinética , Animales , Antineoplásicos/química , Antineoplásicos/farmacocinética , Línea Celular Tumoral , Portadores de Fármacos/administración & dosificación , Ensayos de Selección de Medicamentos Antitumorales , Células HT29 , Humanos , Liposomas/química , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Tamaño de la Partícula , Distribución Aleatoria , Distribución Tisular , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The aim of this research was to evaluate, on a weekly basis, the effects of aflatoxins on the activity of digestive enzymes (alpha-amylase, lipase, and trypsin) in the pancreas as well as on the performance and histology of pancreas in broiler chickens over the course of 42 days. One thousand and eighty 1-day-old male Cobb broilers were divided into four treatments with 18 replicates and 15 birds per replicate (i.e., 270 broilers per treatment). Treatments were established according to the amount of aflatoxins added to the diet, as follows: T1 = 0 mg of aflatoxins per kilogram of feed (mg/kg); T2 = 0.7 mg/kg; T3 = 1.7 mg/kg; and T4 = 2.8 mg/kg. Pancreas sample collection was performed from one bird out of each replicate at 7, 14, 21, 28, 35, and 42 days of experiment, which yielded a total of 18 samples per treatment on each collection. Each sample was homogenized in distilled water, frozen in liquid nitrogen, lyophilized, and stored at -20 C until analysis. Performance parameters (body weight, feed consumption, and feed conversion rate) were measured at 21, 35, and 42 days of experiment. At the end of the experiment (42 days), six birds from each treatment were randomly chosen for histologic evaluation of the pancreas. The presence of aflatoxins in the diet induced a negative effect on all performance parameters. The pancreatic activity of lipase and alpha-amylase were significantly increased in treatments T3 and T4, while the specific activity of trypsin was only affected during treatment T4. In addition, several histologic changes were observed in the pancreas of birds receiving aflatoxin-contaminated feed. Aflatoxins present in the feed determined an increase in the activity of pancreatic enzymes in broilers, affecting the digestibility of the diet, thereby leading to losses in performance and productivity.
Asunto(s)
Aflatoxinas/toxicidad , Peso Corporal/efectos de los fármacos , Pollos/anatomía & histología , Pollos/metabolismo , Metabolismo Energético/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Páncreas/efectos de los fármacos , Aflatoxinas/administración & dosificación , Alimentación Animal/análisis , Animales , Dieta/veterinaria , Femenino , Lipasa/metabolismo , Páncreas/anatomía & histología , Páncreas/enzimología , Factores de Tiempo , Tripsina/metabolismo , alfa-Amilasas/metabolismoRESUMEN
The purpose of this study was to evaluate the effects of feeding corn naturally contaminated with aflatoxin B(1) (AFB(1)) and aflatoxin B(2) (AFB(2)) on serum biochemical parameters, hepatic antioxidant enzyme activities, and pathological lesions of broilers. In total, 1,200 Cobb male broilers were randomly allocated into 5 treatments, with 8 replicates per treatment and 30 birds per replicate, in a 42-d experiment. The dietary treatments were as follows: control, 25, 50, 75, and 100% contaminated corn groups. Results showed that serum aspartate aminotransferase activity in the 75 and 100% contaminated groups were higher than that in the control group on d 21 (P < 0.05). Decreased content of hepatic total protein and increased activities of hepatic glutathione reductase and glutathione-S-transferase were observed as the percentage of contaminated corn increased (P < 0.05). The activity of superoxide dismutase and the content of hepatic malondialdehyde increased when the broilers were fed with more than 50% contaminated corn (P < 0.05). A reduction in glutathione peroxidase level was observed in the AFB(1)- and AFB(2)-contaminated groups on d 21 (P < 0.05). The average pathological lesion scores and apoptosis rate of liver cells increased as the concentration of dietary AFB(1) and AFB(2) increased. Ultrastructural changes were found in the livers of broilers fed 100% contaminated corn. In conclusion, diets containing AFB(1) and AFB(2) could induce pathological lesions in the livers, slightly change the serum biochemical parameters, and damage the hepatic antioxidant functions when the inclusion of AFB(1)- and AFB(2)-contaminated corn reached or exceeded 50%.
Asunto(s)
Aflatoxina B1/toxicidad , Aflatoxinas/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/veterinaria , Pollos , Enfermedades de las Aves de Corral/inducido químicamente , Zea mays/química , Aflatoxina B1/administración & dosificación , Aflatoxina B1/química , Aflatoxinas/administración & dosificación , Aflatoxinas/química , Alimentación Animal/análisis , Animales , Apoptosis , Peso Corporal , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Dieta/veterinaria , Relación Dosis-Respuesta a Droga , Contaminación de Alimentos , Hepatocitos/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , MasculinoRESUMEN
A new aflatoxin, aflatoxin B(2b) (1), together with six known compounds, were isolated from the marine-derived fungus Aspergillus flavus 092008 endogenous with the mangrove plant Hibiscus tiliaceus (Malvaceae). The structure of 1 was determined by the spectroscopic and chemical methods. Compound 1 exhibited a moderate antimicrobial activity against Escherichia coli, Bacillus subtilis and Enterobacter aerogenes, with MIC values of 22.5, 1.7 and 1.1 M, respectively. Compound 1 also showed a weak cytotoxicity against A549, K562 and L-02 cell lines, with IC(50) values of 8.1, 2.0 and 4.2 M, respectively. The results showed that hydration and hydrogenation of (8)-double bond significantly reduces the cytotoxicity of aflatoxins, while the esterification at C-8 increases the cytotoxicity.