RESUMO
This study investigated two outbreaks of spontaneous poisoning by Baccharis coridifolia (Asteraceae) in early-weaned beef calves in Tacuarembó, Uruguay. A total of 34 affected calves showed signs of salivation, anorexia, apathy, marked dehydration, and diarrhea. Deaths occurred 36-72 h after consumption and mortality varied from 37.5% to 43.3% for outbreak 1 and outbreak 2, respectively. The main pathological findings include diffuse severe necrosis of the prestomachs and lymphoid tissues. Ultrastructurally, epithelial cells of the rumen showed swelling, lysis of the organelles, degradation of intercellular attachments, and degradation of the nuclear chromatin. Using LC-MS with diagnostic fragmentation filtering, 56 macrocyclic trichothecenes including glycosyl and malonyl conjugates were identified. The total concentration of macrocyclic trichothecenes, including conjugates, was estimated to be 1.2 ± 0.1 mg/g plant material. This is the first report of these malonyl-glucose conjugates from Baccharis coridifolia.
Assuntos
Baccharis , Tricotecenos , Bovinos , Animais , Tricotecenos/toxicidade , Diarreia , Morte CelularRESUMO
Deoxynivalenol (DON) is a toxic secondary metabolite produced by fungi that contaminates many crops, mainly wheat, maize, and barley. It affects animal health, causing intestinal barrier impairment and immunostimulatory effect in low doses and emesis, reduction in feed conversion rate, and immunosuppression in high doses. As it is very hard to completely avoid DON's production in the field, mitigatory methods have been developed. Biodegradation has become a promising method as new microorganisms are studied and new enzymatic routes are described. Understanding the common root of bacteria with DON degradation capability and the relationship with their place of isolation may bring insights for more effective ways to find DON-degrading microorganisms. The purpose of this review is to bring an overview of the occurrence, regulation, metabolism, and toxicology of DON as addressed in recent publications focusing on animal production, as well as to explore the enzymatic routes described for DON's degradation by microorganisms and the phylogenetic relationship among them.
Assuntos
Tricotecenos/metabolismo , Tricotecenos/toxicidade , Ração Animal , Animais , Bactérias/genética , Bactérias/metabolismo , Biodegradação Ambiental , Contaminação de Alimentos , Microbioma Gastrointestinal/genética , Humanos , FilogeniaRESUMO
The deterioration of food and feed stuffs and toxic intestinal effects due to fungal colonization and concomitant production of mycotoxins is an increasing concern. The development of fungi resistance to many commonly used chemical preservatives adds further alarm. Therefore, effective detoxification methods would be useful in counteracting this problem. Biotransformation/adsorption of mycotoxins by lactic acid bacteria and their metabolites is a promising approach to minimize the deleterious effects of mycotoxins. The objective of the present study was to evaluate the beneficial effects of Lactobacillus plantarum metabolites in reducing deoxynivalenol intestinal toxicity. To achieve this aim, histological, morphometrical and oxidative stress analyses were performed in the intestinal mucosa of piglets exposed to deoxynivalenol alone or associated with two strains (SN1 and SN2) of L. plantarum subsp. plantarum metabolites. Metabolites were obtained after dichloromethane (D) or ethyl acetate (A) extraction. Jejunal explants were exposed to the following treatments for 2 and 4 h a) culture medium (control group); b) deoxynivalenol (DON, 10 µM); c) L. plantarum metabolites DSN1; d) L. plantarum metabolites DSN1+DON; e) L. plantarum metabolites DSN2; f) L. plantarum metabolites DSN2+DON; g) L. plantarum metabolites ASN1; h) L. plantarum metabolites ASN1+DON; i) L. plantarum metabolites ASN2; j) L. plantarum metabolites ASN2+DON. The metabolites were incubated 1 h previously to DON challenge (one and 3 h of exposure). Histological assessment showed DON-treated explants with villi fusion and atrophy, multifocal apical necrosis and cuboid or flattened enterocytes with 2 and 4 h of exposure, while LP metabolites groups individually or associated with DON remained like control. The density of goblet cells in villi and crypts was reduced in DON explants compared to control group with 2 and 4 h of exposure; on the other hand, a significant increase in this parameter was achieved in LP metabolites groups compared to DON. Morphometric evaluation showed no difference in villi height or crypts depth in any treated explants. Overall, oxidative stress response assessments showed that explants exposed to SN1 extracted with dichloromethane and ethyl acetate, and SN2 extracted with dichloromethane reduced superoxide anion production. In conclusion, L. plantarum metabolites induced beneficial effects in intestinal mucosa, reducing the toxic effects of DON on intestinal morphology and oxidative response.
Assuntos
Lactobacillus plantarum , Micotoxinas , Tricotecenos , Animais , Jejuno , Suínos , Tricotecenos/toxicidadeRESUMO
The impact of deoxynivalenol (DON) upon intestinal tissue of broilers was assessed by using jejunal explants in Ussing chambers and analyzing histopathological and immunohistochemical parameters; this system was also applied to evaluate the efficacy of an antimycotoxins additive (AMA). The explants were subjected to the following treatments within each experiment for 120 min: Experiment 1) T1 (control) - buffer solution, and T2 - 10 mg/L DON; and Experiment 2) T1 (control) - buffer solution, T2 - 10 mg/L DON, T3 - AMA (0.5%), and T4 - 10 mg/L DON + 0.5% AMA. In Experiment 1, DON triggered a reduction in the size of enterocytes as well as of their nuclei, an increase in cytoplasmic vacuolization and apical denudation of villi. Apoptotic cells count was also greater in DON-exposed explants. In Experiment 2, the AMA mitigated DON harmful effects; cytoplasmic vacuolization of enterocytes was reduced and the size of their nuclei was preserved. The additive also promoted a partial decrease in microvillus integrity, in size of enterocytes and in apoptotic cells count. The tested ex vivo model demonstrated the impact of DON upon the intestine as well as the efficacy of the AMA against its damaging effects.
Assuntos
Galinhas , Tricotecenos , Ração Animal/análise , Animais , Intestinos , Jejuno , Tricotecenos/toxicidadeRESUMO
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
BACKGROUND: Deoxynivalenol (DON), a mycotoxin produced by Fusarium spp., is commonly found in cereals ingested by humans and animals. Its ingestion is correlated with hepatic, hematologic, renal, splenic, cardiac, gastrointestinal, and neural damages, according to dose, duration of exposure and species. In this work, the effects of the ingestion of DON-contaminated diet at concentrations considered tolerable for human and animal intake were assessed. METHODS: Male Wistar rats aging 21 days were allotted to five groups that were given, for 42 days, diets contaminated with different concentrations of DON (0, 0.2, 0.75, 1.75, and 2 mg kg-1 of chow). Food ingestion, bodyweight, oxidative status and morphometric analyses of gliocytes, and neurons of jejunal myenteric ganglia were recorded. KEY RESULTS: At these concentrations, there was no food rejection, decrease in bodyweight gain, changes in oxidative status, or loss of either neurons or gliocytes. However, DON decreased gliocyte area, general neuronal population, nitrergic, cholinergic and NADH-diaphorase positive subpopulations and, as a result, ganglion area. CONCLUSIONS & INFERENCES: It was concluded that, even in the absence of visible effect, DON exposure reduces cell body area of gliocytes and neurons of the myenteric plexus of the rat jejunum.
Assuntos
Jejuno/efeitos dos fármacos , Plexo Mientérico/efeitos dos fármacos , Neuroglia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Tricotecenos/toxicidade , Animais , Dieta , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Wistar , Tricotecenos/administração & dosagemRESUMO
The purpose of the present study was to investigate the effects of phytic acid (IP6) on morphological and immunohistochemical parameters and oxidative stress response in intestinal explants of pigs exposed to fumonisin B1 (FB1) and/or deoxynivalenol (DON). The jejunal explants were exposed to the following treatments: vehicle, IP6 5 mM, DON 10 µM, FB1 70 µM, DON 10 µM + FB1 70 µM, DON 10 µM + IP6 5 mM, FB1 70 µM + IP6 5 mM, and DON 10 µM + FB1 70 µM + IP6 5 mM. The decrease in villus height and goblet cell density was more evident in DON and DON + FB1 treatments. In addition, a significant increase in cell apoptosis and cell proliferation and a decrease in E-cadherin expression were observed in the same groups. DON and FB1 exposure increased cyclooxygenase-2 expression and decreased the cellular antioxidant capacity. An increase in lipid peroxidation was observed in DON- and FB1-treated groups. IP6 showed beneficial effects, such as a reduction in intestinal morphological changes, cell apoptosis, cell proliferation, and cyclooxygenase-2 expression, and an increase in E-cadherin expression when compared with DON, FB1 alone, or DON and FB1 in association. IP6 inhibited oxidative stress and increased the antioxidant capacity in the explants exposed to mycotoxins.
Assuntos
Fumonisinas/toxicidade , Intestinos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ácido Fítico/farmacologia , Tricotecenos/toxicidade , Animais , Apoptose/efeitos dos fármacos , Contagem de Células , Proliferação de Células/efeitos dos fármacos , Células Caliciformes/efeitos dos fármacos , Intestinos/patologia , SuínosRESUMO
Deoxynivalenol (DON) is a mycotoxin that affects the intestinal morphology of animals, impairing nutrient intake and growth. On the other hand, dietary supplementation with functional oligosaccharides as chito-oligosaccharides (COS) has shown positive effects on the intestinal health of piglets. Therefore, the objective of the present study was to evaluate the effect of low doses of COS in preventing DON-induced intestinal histological changes, using a swine jejunal explant technique. The intestinal explants were incubated at 37 °C in culture medium for 4 h and exposed to the following treatments: (a) control (only culture medium), (b) DON (10 µM), (c) 25COS (0.025 mg·mL−1 of COS); (d) 50COS (0.05 mg·mL−1 of COS); (e) 25COS plus DON (25COS + DON); (f) 50COS plus DON (50COS + DON). Explants exposed to COS presented intestinal morphology similar to control samples. DON induced a significant decrease in the histological score as a consequence of moderate to severe histological changes (apical necrosis, villi atrophy, and fusion) and a significant decrease in morphometric parameters (villi height, crypt depth, villi height:crypt depth ratio, and goblet cells density). The intestinal morphology of samples exposed to COS + DON remained similar to DON treatment. In conclusion, low levels of COS did not counteract DON-induced intestinal lesions.
Assuntos
Jejuno/efeitos dos fármacos , Oligossacarídeos/farmacologia , Tricotecenos/toxicidade , Animais , Jejuno/patologia , SuínosRESUMO
Probiotics have been explored to stimulate gut health in weaned pigs, when they started to consume solid diet where mycotoxins could be present. The aim of this study was to evaluate the effect of Lactobacillus rhamnosus RC007 on the intestinal toxicity of deoxynivalenol (DON) in an ex vivo model. Jejunal explants, obtained from 5-week-old crossbred castrated male piglets, were kept as control, exposed for 3 h to 10 µM DON, incubated for 4 h with 109 CFU/mL L. rhamnosus, or pre-incubated 1 h with 109 L. rhamnosus and exposed to DON. Histological lesions were observed, para- and transcellular intestinal permeability was measured in Ussing chambers. The expression levels of mRNA encoding six inflammatory cytokines (CCL20, IL-10, IL-1ß, TNFα, IL-8 and IL-22) were determined by RT-PCR. The expressions of the phosphorylated MAP kinases p42/p44 and p38 were assessed by immunoblotting. Exposure to DON induced histological changes, significantly increased the expression of CCL20, IL-1ß, TNFα, IL-8, IL-22 and IL-10, increased the intestinal paracellular permeability and activated MAP kinases. Incubation with L. rhamnosus alone did not have any significant effect. By contrast, the pre-incubation with L. rhamnosus reduced all the effects of DON: the histological alterations, the pro-inflammatory response, the paracellular permeability and the phosphorylation of MAP kinases. Of note, L. rhamnosus did not adsorb DON and only slightly degrade the toxin. In conclusion, L. rhamnosus RC007 is a promising probiotic which, included as feed additive, can decrease the intestinal toxicity of DON.
Assuntos
Jejuno/efeitos dos fármacos , Jejuno/microbiologia , Lacticaseibacillus rhamnosus , Probióticos , Tricotecenos/toxicidade , Ração Animal , Animais , Citocinas/metabolismo , Técnicas In Vitro , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Permeabilidade , Fosforilação , SuínosRESUMO
In the present study, histological, morphometrical and ultrastructural analysis were performed to investigate intestinal mucosa changes in piglets exposed to deoxynivalenol alone or associated with two strains of Lactobacillus plantarum and the respective culture supernatants. Jejunal explants were incubated for 4h in culture medium with a) only culture medium (DMEM, control group), b) deoxynivalenol (DON, 10µM), c) heat-inactivated Lactobacillus plantarum strain1 - LP1 (1.1×108 CFU/ml) plus DON, d) heat-inactivated Lactobacillus plantarum strain2-LP2 (2.0×109 CFU/ml) plus DON, e) heat-inactivated Lactobacillus plantarum strain1 culture supernatant (CS1) plus DON, and f) heat-inactivated Lactobacillus plantarum strain1 culture supernatant (CS1) plus DON. Explants exposed to DON and DON plus LP1 and LP2 showed a significant increase in histological changes (mainly villi atrophy and apical necrosis) and a significant decrease in villi height when compared to unexposed explants. However, explants treated with CS1+DON and CS2+DON remained similar to the control group both in histological and morphometrical aspects. DON also induced a significant decrease in goblet cell density compared to control whereas CS1+DON treatment induced an increase in the number of goblet cells in comparison to DON explants. In addition, ultrastructural assessment showed control, CS1+DON and CS2+DON explants with well delineated finger shape villi, meanwhile DON-treated, LP1+DON and LP2+DON explants showed a severe villi atrophy with leukocytes exudation on the intestinal surface. Taken together, our results indicate that the culture supernatant treatment reduced the toxic effects induced by DON on intestinal tissue and may contribute as an alternative strategy to reduce mycotoxin toxicity.