RESUMO
Aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are mycotoxins widely found as cereal contaminants, and their co-consumption is associated with liver cancer. Both are immunotoxic, but their interactions have been little studied. This work was aimed to evaluate in mouse spleen mononuclear cells (SMC) the effects of the exposure to AFB1 (5-50 µM), FB1 (25-250 µM), and AFB1-FB1 mixtures (MIX) on the in vitro differentiation of regulatory T cells (Treg and Tr1-like) and Th17 cells, as well as elucidate the contribution of aryl hydrocarbon receptor (Ahr) in such effects. AFB1 and mainly MIX induced cytotoxicity in activated CD4 cells via Ahr signaling. AFB1 (5 µM) increased the Treg cell differentiation, but its combination with FB1 (25 µM) also reduced Th17 cell expansion by Ahr-dependent mechanisms. Therefore, this mixture could enhance the Treg/Th17 cell ratio and favor immunosuppression and escape from tumor immunosurveillance to a greater extent than individual mycotoxins. Whereas, AFB1-FB1 mixtures at medium-high doses inhibited the Tr1-like cell expansion induced by the individual mycotoxins and affected Treg and Th17 cell differentiation in Ahr-independent and dependent manners, respectively, which could alter anti-inflammatory and Th17 immune responses. Moreover, individual FB1 altered regulatory T and Th17 cell development independently of Ahr. In conclusion, AFB1 and FB1 interact by modifying Ahr signaling, which is involved in the immunotoxicity as well as in the alteration of the differentiation of Treg, Tr1-like, and Th17 cells induced by AFB1-FB1 mixtures. Therefore, Ahr is implicated in the regulation of the anti- and pro-inflammatory responses caused by the combination of AFB1 and FB1.
Assuntos
Aflatoxina B1 , Diferenciação Celular , Fumonisinas , Receptores de Hidrocarboneto Arílico , Linfócitos T Reguladores , Células Th17 , Receptores de Hidrocarboneto Arílico/metabolismo , Aflatoxina B1/toxicidade , Animais , Células Th17/efeitos dos fármacos , Linfócitos T Reguladores/efeitos dos fármacos , Fumonisinas/toxicidade , Camundongos , Diferenciação Celular/efeitos dos fármacosRESUMO
Mycotoxins present a significant health concern within the animal-feed industry, with profound implications for the pig-farming sector. The objective of this study was to evaluate the efficacy of two commercial adsorbents, an organically modified clinoptilolite (OMC) and a multicomponent mycotoxin detoxifying agent (MMDA), to ameliorate the combined adverse effects of dietary aflatoxins (AFs: sum of AFB1, AFB2, AFG1, and AFG2), fumonisins (FBs), and zearalenone (ZEN) at levels of nearly 0.5, 1.0, and 1.0 mg/kg, on a cohort of cross-bred female pigs (N = 24). Pigs were randomly allocated into six experimental groups (control, mycotoxins (MTX) alone, MTX + OMC 1.5 kg/ton, MTX + OMC 3.0 kg/ton, MTX + MMDA 1.5 kg/ton, and MTX + MMDA 3.0 kg/ton), each consisting of four individuals, and subjected to a dietary regimen spanning 42 days. The administration of combined AFs, FBs, and ZEN reduced the body-weight gain and increased the relative weight of the liver, while there was no negative influence observed on the serum biochemistry of animals. The supplementation of OMC and MMDA ameliorated the toxic effects, as observed in organ histology, and provided a notable reduction in residual AFs, FBs, and ZEN levels in the liver and kidneys. Moreover, the OMC supplementation was able to reduce the initiation of liver carcinogenesis without any hepatotoxic side effects. These findings demonstrate that the use of OMC and MMDA effectively mitigated the adverse effects of dietary AFs, FBs, and ZEN in piglets. Further studies should explore the long-term protective effects of the studied adsorbent supplementation to optimize mycotoxin management strategies in pig-farming operations.
Assuntos
Ração Animal , Micotoxinas , Animais , Feminino , Aflatoxinas/toxicidade , Contaminação de Alimentos/análise , Contaminação de Alimentos/prevenção & controle , Fumonisinas/toxicidade , Micotoxinas/análise , Micotoxinas/toxicidade , Suínos , Zearalenona/análise , Ração Animal/efeitos adversos , Ração Animal/microbiologia , Microbiologia de AlimentosRESUMO
Mycotoxins are toxic and carcinogenic metabolites produced by groups of filamentous fungi that colonize food crops. Aflatoxin B1 (AFB1), ochratoxin A (OTA) and fumonisin B1 (FB1) are among the most relevant agricultural mycotoxins, as they can induce various toxic processes in humans and animals. To detect AFB1, OTA and FB1 in the most varied matrices, chromatographic and immunological methods are primarily used; however, these techniques are time-consuming and expensive. In this study, we demonstrate that unitary alphatoxin nanopore can be used to detect and differentiate these mycotoxins in aqueous solution. The presence of AFB1, OTA or FB1 inside the nanopore induces reversible blockage of the ionic current flowing through the nanopore, with distinct characteristics of blockage that are unique to each of the three toxins. The process of discrimination is based on the residual current ratio calculation and analysis of the residence time of each mycotoxin inside the unitary nanopore. Using a single alphatoxin nanopore, the mycotoxins could be detected at the nanomolar level, indicating that alphatoxin nanopore is a promising molecular tool for discriminatory analysis of mycotoxins in aqueous solution.
Assuntos
Aflatoxinas , Fumonisinas , Micotoxinas , Nanoporos , Ocratoxinas , Animais , Humanos , Ocratoxinas/análise , Fumonisinas/toxicidade , Aflatoxinas/análise , Micotoxinas/análise , Aflatoxina B1/análiseRESUMO
Fumonisins are naturally occurring mycotoxins that contaminate food for human and animal consumption. They have neurotoxic effects, but the mechanisms by which these toxins affect the nervous system are not fully known. In the present study, male Wistar rats were fed between 21 and 63 days of age with diets that contained fumonisins B1+B2 at 0, 1, and 4â mg/kg. The following variables were assessed: food consumption, growth, body weight gain, and blood parameters. Morphoquantitave analyses of the most metabolically active myenteric neurons were performed, detected by NADH-diaphorase activity. Nitrergic neurons were detected by NADPH-diaphorase activity. The fumonisin-containing diets did not significantly alter food consumption or the body or plasma parameters. These diets decreased the metabolic activity of jejunal myenteric neurons, reducing neuronal density of the most metabolic active neurons by 30.8% and the cell body area by 4.3%. The diets also decreased the cell body area of nitrergic neurons by 22.1%. The effects of fumonisin B1 on the respiratory metabolism of isolated mitochondria in the brain and liver were also assessed. A decrease in oxygen consumption up to a 29% in the brain and 38% in the liver was observed in mitochondrial isolates to which 50â µM fumonisin B1 was added. The decrease in respiratory activity that was triggered by exposure to fumonisins was related to the lower metabolic activity of myenteric neurons, which had a negative impact on neuroplasticity of the enteric nervous system.
Assuntos
Fumonisinas , Micotoxinas , Animais , Dieta , Fumonisinas/toxicidade , Masculino , Neurônios , Ratos , Ratos WistarRESUMO
The aim of this study was to determine whether the addition of curcumin (free and encapsulated) to chick feed would minimize the negative effects on health and performance caused by daily intake of fumonisin. We used 50 birds, divided into five treatments: CP, basal diet with 600 mg/kg of fumonisin, with antibiotic and coccidiostatic agent; CU, 600 mg/kg of fumonisin and 50 mg/kg of curcumin; NC5, feed with 600 mg/kg of fumonisin and 5 mg of nano-curcumin/kg of feed; NC10, feed with 600 mg/kg of fumonisin and 10 mg of nano-curcumin/kg of feed; and CN, fumonisin-free diet, with antibiotic and coccidiostatic. We measured weights, weight gain, and serum biochemistry, as well as antioxidant and oxidant activities. Lower body weight and weight gain were observed in chicks that received feed with fumonisin; curcumin did not minimize this negative effect. Lower glucose and triglyceride levels were also observed in the NC10 group, while the highest cholesterol levels were observed in all groups of birds that consumed fumonisin compared to the CN group. Uric acid levels were significantly lower in CP than in CN. Levels of liver enzymes were higher in CP than in CN. The highest levels of thiobarbituric acid reactive substances were found in CP and CU, whereas ROS was higher in CU compared to CN. Superoxide dismutase activity was significantly lower in CP, while glutathione S-transferase activity was higher in the CP group. Catalase activity was lower in groups of birds that consumed fumonisin compared to CN. Taken together, these findings suggest that intake of curcumin-loaded nanocapsules (10 mg/kg) had hepaprotective and antioxidant effects in chicks artificially intoxicated with fumonisin, minimizing the negative effects caused by this mycotoxin.
Assuntos
Curcumina , Fumonisinas , Fusarium , Nanocápsulas , Ração Animal/análise , Animais , Galinhas , Curcumina/metabolismo , Curcumina/farmacologia , Fumonisinas/toxicidade , Fígado/metabolismo , Estresse OxidativoRESUMO
Mycotoxins are toxic secondary metabolites produced by fungus which cause worldwide concern regarding food and feed safety. Ochratoxin A (OTA), fumonisin B1 (FB1) and deoxynivalenol (DON) are some of the main mycotoxins and oxidative stress is the main mechanism of toxicity. Thereby, this study investigates the in vitro cytoprotective effects of curcumin (CUR) and silymarin (SIL) - known for their strong antioxidant activity - in PK-15 cells exposed to OTA, FB1 and DON. Pretreatment with CUR and SIL enhanced the viability of cells exposed to the mycotoxins (P < 0.001) and attenuated reactive oxygen species (ROS) formation by DON (P < 0.01), partially reduced ROS formation by FB1 (P < 0.001), but not OTA. CUR significantly decreased apoptosis in cells exposed to DON (P < 0.01) but was not able to prevent apoptosis in cells exposed to OTA and FB1. Whereas SIL was able to prevent apoptosis in PK-15 cells exposed to FB1 and DON (P < 0.01) but was not able to decrease apoptosis in cells exposed to OTA. In summary, these data indicate that curcumin and silymarin are able to provide cytoprotection against toxicity induced by OTA, FB1 and DON in PK-15 cells.
Assuntos
Curcumina/farmacologia , Micotoxinas/toxicidade , Substâncias Protetoras/farmacologia , Silimarina/farmacologia , Apoptose , Sobrevivência Celular , Fumonisinas/toxicidade , Fungos , Ocratoxinas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Tricotecenos/toxicidadeRESUMO
Fusarium verticillioides is often responsible for contamination of poultry feed with the mycotoxin fumonisin. The aim of this study was to determine whether oxidative stress caused by intake of fumonisin-contaminated feed affects broiler performance at an early stage of development, as well as to test whether the addition of açai residue flour to contaminated feed would minimize these negative effects of redox metabolism. Birds were divided into four groups, with four repetitions of five animals each: control (TC) - birds that received basal feed; TCA treatment - basal feed supplemented with 2% açai flour; TF treatment - feed experimentally contaminated with fumonisin (10 ppm); TFA treatment - fumonisin-contaminated feed (10 ppm) and supplemented with açai fluor (2%). The experiment lasted 20 days, that is, the first 20 days of the chicks' lives. At the end of the experiment, the birds were weighed, and blood, intestine and liver samples were collected. The TCA and TFA had greater body weights and weight gain than did TF. Further, TCA and TFA had lower feed conversion than did TF. Açai flour intake (TCA and TFA) stimulated albumin synthesis and reduced serum AST activity. Nitrate/nitrite (NOx) levels were higher in serum of fumonisin-challenged (TF) birds than in groups; NOx levels were also higher in the livers of all test groups (TF, TCA and TFA) than in TC. Serum glutathione S-transferase (GST) activity was lower in fumonisin-consuming groups (TF and TFA); this was different from what occurred in the liver, that is, higher GST activity in TF and lower activity in TFA than in TC. Catalase activity (CAT) was also higher in the fumonisin-challenged groups (TF and TFA) and the groups supplemented with açai flour (TCA) than in TC. Serum reactive species (RS) and TBARS (lipid peroxidation) levels in the liver were lower in birds supplemented with açai flour and exposed to fumonisin. These data suggest that the addition of açai flour in the feed of early chickens improves animal performance and minimizes the effects of hepatic oxidative stress in birds fed fumonisin-contaminated feed.
Assuntos
Galinhas/crescimento & desenvolvimento , Euterpe , Fumonisinas/toxicidade , Fígado , Extratos Vegetais/farmacologia , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais , Farinha , Fusarium/metabolismo , Fusarium/patogenicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Micotoxinas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Doenças das Aves Domésticas/metabolismo , Aumento de Peso/efeitos dos fármacosRESUMO
Glycerol monolaurate (GML) is composed of lauric acid and glycerol. Research has shown that such organic acids can minimize negative effects caused by mycotoxins. Therefore, the objective of this study was to determine whether adding GML (free or encapsulated) to chick feed minimizes the effects of natural contamination by fumonisin (Fusarium verticillioides), evaluating parameters such as biochemistry, antioxidant properties, histological analysis and chick growth. Were weighed 84 chicks of the Cobb 500 strain and randomly distributed them into six groups of two replicates each (n = 14). The F group consumed feed containing fumonisin (levels 400 ppb), with no performance enhancer; F + ZB- feed with fumonisin (levels 400 ppb) + zinc bacitracin; F + GLM100 - feed with fumonisin (levels 400 ppb) + 100 mg of GML/kg of feed; F + NGLM4 - feed with fumonisin (levels 400 ppb) + 4 mg GML/kg in nanocapsules added to the feed; F + NGLM8 - fumonisin feed (levels 400 ppb) + 8 mg GML/kg in nanocapsules in the feed; and F0 - fumonisin-free feed (negative control) + zinc bacitracin. The body weights of birds fed with feed fumonisin-contaminated feed (F, F + ZB, F + GLM100, F + NGLM4 and F + NGLM8) were significantly lower (P < 0.05) than those of the negative control (F0), despite the use of GML (free and nanoencapsulated). Serum levels of triglycerides, globulins and cholesterol were significantly lower in the F0 group than in the other groups (P < 0.05), except for the F + NGLM8 group. Significantly greater levels of lipid peroxidation were observed in livers in the groups that consumed fumonisin than in the control group (F0) (P < 0.05). Serum levels of reactive oxygen species were significantly lower in groups F + NGLM8 and F0 than in the other treatments (P < 0.05). Superoxide dismutase activity was significantly greater in groups F + NGLM8 and F0 than in groups F, F + ZB and F + NGLM4. Hepatic catalase activity was significantly lower in birds that consumed contaminated feed (F, F + ZB, F + GLM100, F + NGLM4 and F + NGLM8) than in the control group (F0). Greater hepatic glutathione S-transferase activity was observed in the F + NGLM8 group than in the F0 group. Despite changes in cellular lesions in the liver, no histological changes were observed in the liver or intestines, even though visually there was yellowing of the liver. Taken together, the data suggest that free or nano-encapsulated GML did not minimize oxidative stress caused by fumonisin, and consequently, these birds had less weight gain.
Assuntos
Fumonisinas , Ração Animal/análise , Animais , Galinhas , Dieta , Fumonisinas/toxicidade , Fusarium , Lauratos , Fígado , MonoglicerídeosRESUMO
Fusarium verticillioides is often responsible for contamination of poultry feed with the mycotoxin fumonisin. The objective of the study was to determine whether fumonisin-contaminated feed in the early phase of broiler chicks causes oxidative imbalances and interferes with weight gain. One-day-old male Cobb 500 broiler chicks (n = 80) were divided into four treatments of 20 birds each, all of which were fed basal feed until the 11th day of age. From day 12, some birds were challenged with fumonisin in the feed: Control (T0) continued receiving the basal ration; treatments T1, T2, and T3 were given feed experimentally contaminated with fumonisin at concentrations of 2.5 ppm, 5 ppm and 10 ppm, respectively. After the 5th (day 17) and 10th (day 21) days, ten birds from each treatment were euthanized for blood and tissue collection to measure histopathological, biochemical and oxidative stress markers. All animals were weighed individually at the beginning of the experiment (day 12), and at 17 and 21 days of age. Birds that ingested 10 ppm of fumonisin (T3) had lower (P < 0.05) weight gain compared to those in T0. At 21 days, the body weights of the T1, T2 and T3 chicks were 1.3%, 8.97% and 18.7% lower, respectively, than those of T0. No histological lesions in the livers were observed for any treatment; however, higher levels of reactive oxygen species (ROS: day 21) and lipoperoxidation (LPO: days 17 and 21) were observed, associated with lower liver activity of the enzymes superoxide dismutase (SOD: day 21), glutathione peroxidase (GPx: day 17 and 21) and glutathione S-transferase (GST: day 21) when birds consumed 5 or 10 ppm of fumonisin. In serum, LPO levels and SOD and GPx activities were lower for groups consuming high doses of fumonisin in the diet (T2 and T3); ROS levels and GST activity were higher in these birds. Birds that consumed fumonisin-containing diets had lower levels of alanine aminotransferase, total protein and albumin (T3); as well as lower serum glucose levels (days 17 and 21), uric acid and triglycerides (day 21) in T3 than in T0. At 21 days, there were smaller crypt sizes and intestinal villi in birds that consumed high levels of fumonisin. These results suggest that fumonisin (10 ppm) in chick diet causes hepatic oxidative stress and impairs intestinal health, consequently negatively affecting weight gain.
Assuntos
Fumonisinas , Fusarium , Doenças das Aves Domésticas , Ração Animal , Animais , Galinhas , Dieta , Ingestão de Alimentos , Fumonisinas/toxicidade , Masculino , Doenças das Aves Domésticas/induzido quimicamente , Aumento de PesoRESUMO
The trend toward using plant-based ingredients in aquafeeds has raised important concerns for aquaculture owing to the negative impacts of mycotoxins on fish health; with emphasis for contamination by fumonisin B1 (FB1). The brain is an important target of FB1; however, study of the pathways linked to brain damage is limited to an analysis of histopathological alterations. Reports have demonstrated the protective effects of dietary supplementation with diphenyl diselenide (Ph2Se2) in the brains of fish subjected to several environmental insults; nevertheless, its neuroprotective effects in fish fed with diets contaminated with FB1 remain unknown. Therefore, the aim of this study was to evaluate whether oxidative damage may be a pathway associated with FB1-induced neurotoxicity, as well as to evaluate whether dietary supplementation with Ph2Se2 prevents or reduces FB1-mediated brain oxidative damage in silver catfish. Brain reactive oxygen species (ROS), lipid peroxidation (LOOH) and protein carbonylation increased on day 30 post-feeding in animals that received FB1-contaminated diets compared to the control group, while brain antioxidant capacity against peroxyl radicals (ACAP) levels and catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities were lower. Diphenyl diselenide dietary supplementation avoid increases in brain ROS levels, as well minimizing the augmentation of LOOH levels. Furthermore, Ph2Se2 prevented impairment of brain ACAP levels, as well as GPx and GST activities elicited by FB1-contaminated diets. These data suggest that dietary supplementation with 3 mg/kg Ph2Se2 prevented FB1-induced brain damage in silver catfish, and this protective effect occurred through avoided of excessive ROS production, as well as via prevention of brain lipid damage. Furthermore, Ph2Se2 exerted its neuroprotective effects via ameliorative effects on the enzymatic and non-enzymatic antioxidant defense systems, and may be an approach to prevent FB1-induced brain oxidative stress; however, is not an alternative to prevent the impairment on performance caused by FB1.