Fumonisins : Toxicokinetics, mechanism of action and toxicity

Fumonisin B(1) (FB(1)) is a mycotoxin produced by the fungus Fusarium verticillioides, which commonly infects corn and other agricultural products. Fusarium species can also be found in moisture-damaged buildings, and, therefore, exposure of humans to Fusarium mycotoxins including FB(1) may take place. FB(1) bears a clear structural similarity to the cellular sphingolipids, and this similarity has been shown to disturb the metabolism of sphingolipids by inhibiting the enzyme ceramide synthase leading to accumulation of sphinganine in cells and tissues. FB(1) is neurotoxic, hepatotoxic, and nephrotoxic in animals, and it has been classified as a possible carcinogen to humans. The cellular mechanisms behind FB(1)-induced toxicity include the induction of oxidative stress, apoptosis, and cytotoxicity, as well as alterations in cytokine expression. The effects of FB(1) on different parameters vary markedly depending on what types of cells are studied or what species they originate from. These aspects are important to consider when evaluating the toxic potential of FB(1).

A review of the toxic effects and mechanisms of action of fumonisin B1.

Fumonisin B1 (FB1) is a mycotoxin that commonly occurs in maize. FB1 causes a variety of toxic effects in different animal species and has been implicated as a contributing factor of esophageal cancers in humans. In the present study, we examined the effect of dietary exposure to FB1 on intestinal colonization by pathogenic Escherichia coli associated with extraintestinal infection. Three-week-old weaned pigs were given FB1 by gavage as a crude extract or as a purified toxin at a dose of 0.5 mg/kg of body weight daily for 6 days. On the last day of the toxin treatment, the pigs were orally inoculated with an extraintestinal pathogenic E. coli strain. All animals were euthanized 24 h later, necropsies were performed, and tissues were taken for bacterial counts and light microscopic examination. Ingestion of FB1 had only a minimal effect on animal weight gain, did not cause any macroscopic or microscopic lesions, and did not change the plasma biochemical profile. However, colonization of the small and large intestines by an extraintestinal pathogenic E. coli strain was significantly increased. Our results show that FB1 is a predisposing factor to infectious disease and that the pig can be used as a model for the study of the consequences of ingesting mycotoxin-contaminated food.

Mycotoxin Fumonisin B1 Increases Intestinal Colonization by Pathogenic Escherichia coli in Pigs

Mycotoxins are secondary metabolites of fungi that grow on a variety of substrates. Due to their high consumption of cereals and their sensitivity, pigs are highly impacted by the presence of mycotoxins. At the European level, regulations and recommendations exist for several mycotoxins in pig feed. Among these toxins, fumonisin B1 (FB1), and deoxynivalenol (DON) have a great impact on the intestine and the immune system. Indeed, the intestine is the first barrier to food contaminants and can be exposed to high concentrations of mycotoxins upon ingestion of contaminated feed. FB1 and DON alter the intestinal barrier, impair the immune response, reduce feed intake and weight gain. Their presence in feed increases the translocation of bacteria; mycotoxins can also impair the immune response and enhance the susceptibility to infectious diseases. In conclusion, because of their effect on the intestine, FB1 and DON are a major threat to pig health, welfare and performance.

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Impact of two mycotoxins deoxynivalenol and fumonisin on pig intestinal health

At the Mirador farm of the Patricia Pilar Parish km 41 on the way Santo Domingo Quevedo, located in the Buena Fe Canton, Los Rios Province, three levels of silo banana were evaluated in 5-7-yr crossbred Sahiwal cows at the second third of lactation (8, 12, and 16 kg/animal/day) compared to a control treatment (forage feeding) through a completely at random block design (DBCA) and evaluating different productive features over the120 days of the investigation. Statistical differences (P<0.05) between the different evaluated treatments were established, showing that the best level of the silage surplus banana use was 16 kg with a higher weight gain and milk production in the animals supplemented with this level with 18.50 kg weight and 13.54 l milk/cow/day production. On the other hand the lowest productive response was obtained in the control group with a weight gain of 14.75 kg and 8.28 l milk/cow/day production. The benefit-cost index was higher upon using 16 kg silage surplus banana reaching an index of 1.12 USD while in the control group an index of only 1.10 USD was determined. This is why it is recommended to use 16 kg/animal/day silage surplus banana as it has shown production efficiency improving considerably the economic yields. LISTA DE CUADROS No. Pag. 1. DIGESTIBILIDAD DE LA BANANA. 14 2. PERFIL NUTRITIVO DEL BANANO. 15 3. SILO DE RECHAZO ENTERO. 18 4. ENSILAJE DE BANANO FRESCO. 19 5. CONDICIONES METEOROLOGICAS EN LA HACIENDA “MIRADOR DE ILA”. 27 6. ESQUEMA DEL EXPERIMENTO. 29 7. EVALUACION DE LA PRODUCCION DE ENSILAJE DE RECHAZO DE BANANO PARA LA ALIMENTACION DE VACAS LECHERAS. 34 8. RESPUESTA BIOLOGICA DE VACAS SAHIWAL MESTIZAS EN EL SEGUNDO TERCIO DE LACTANCIA, ANTE LA SUPLEMENTACION CON DIFERENTES NIVELES DE ENSILAJE DE RECHAZO DE BANANO. 36 9. CALIDAD DE LA LECHE DE VACAS SAHIWAL MESTIZAS EN EL SEGUNDO TERCIO DE LACTANCIA, ANTE LA ALIMENTACION CON PASTO ESTRELLA Y DIFERENTES NIVELES DE ENSILAJE DE RECHAZO DE BANANO. 52 10. COMPARACION DE LA CALIDAD NUTRITIVA DE LOS ALIMENTOS UTILIZADOS, EN VACAS SAHIWAL EN EL SEGUNDO TERCIO DE LACTANCIA. 54 11. CALIDAD ENERGETICA DE ALIMENTOS UTILIZADOS, EN VACAS SAHIWAL EN EL SEGUNDO TERCIO DE LACTANCIA. 55 12. EVALUACION ECONOMICA DE LA UTILIZACION DE DIFERENTES NIVELES DE ENSILAJE DE RECHAZO DE BANANO EN LA ALIMENTACION DE VACAS SAHIWAL EN EL SEGUNDO TERCIO DE LACTANCIA. 56 LISTA DE GRAFICOS No. Pag. 1. Peso inicial y final de vacas Sahiwal suplementadas con diferentes niveles de ensilaje de rechazo de banano 37 2. Evolucion del peso de vacas Sahiwal suplementadas con diferentes niveles de ensilaje de rechazo de banano 38 3. Ganancia de peso en vacas Sahiwal suplementadas con diferentes niveles de ensilaje de rechazo de banano 40 4. Consumo total y diario de Ensilaje de rechazo de banano en vacas Sahiwal 42 5. Consumo total y diario de forraje (Pasto estrella) en vacas Sahiwal suplementadas con diferentes niveles de ensilaje de rechazo de banano 44 6. Factor Efectivo de Utilizacion del Pastizal ante la suplementacion con diferentes niveles de ensilaje de rechazo de banano 46 7. Consumo total de Materia Seca en vacas Sahiwal suplementadas con diferentes niveles de ensilaje de rechazo de banano 47 8. Produccion lactea en vacas Sahiwal suplementadas con diferentes niveles de ensilaje de rechazo de banano 49 9. Linea de tendencia de la regresion para la produccion de leche en vacas Sahiwal suplementadas con diferentes niveles de ensilaje de rechazo de banano 51 10. Relacion de Beneficio / Costo en para la utilizacion de diferentes niveles de ensilaje de rechazo de banano 57

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Escuela superior politécnica de chimborazo

In Hungary almost 70% of mould-affected maize inspected since 1993 was found to be contaminated with fumonisin B1 (FB1) (mean 26-865 mg/kg; maximum 98-751 mg/kg), the degree of this contamination was found to increase from year to year (Fazekas et al, 1997b) In this experiment, in order to define tolerance limit values, the effect of exposing weaned piglets to FB1 in low doses over a 4-week period was examined The experiment was performed with 20 weaned barrows of Danish Landrace breed After a 5-day adaptation period cultures of the fungus Fusarium moniliforme were mixed into the animals' feed in concentrations that resulted in a daily intake of fumonisin B1 of 0, 10, 20 and 40 mg/kg feed Feeding with the toxin was observed to exert no significant effect on body weight gain or feed consumption in the animals, no clinical signs were observed and no mortality traceable to toxic effects occurred In computer tomography examinations performed in the second and fourth weeks mild and more severe pulmonary oedema was diagnosed in the experimental animals The processes developing in the pulmonary parenchyma were corroborated by the mathematical and statistical evaluation procedures applied The haematological parameters examined revealed no change attributable to toxic effects, while with respect to the biochemical parameters, an increase in aspartate aminotransferase (AST) activity dependent on dosage, indicating a pathological change in the liver, was ascertained in all three experimental groups The free sphinganine to sphingosine ratio (SA/SO), which is regarded as the most sensitive bioindicator of fumonisin toxicosis, showed an increase proportionate to toxin concentration for all three dosages Dissection revealed mild cases of pulmonary oedema in three of the animals given doses of 10 ppm (n = 4), two mild and two severe cases in those exposed to 20 ppm (n = 5), and severe cases in all five animals given 40 ppm The oedema of non-inflammatory origin was confirmed by histopathological examinations The findings of this experiment which indicate that in this study FB1 administered in substantially lower concentrations than those reported in the literature resulted in severe pathological changes, point to the importance of studies involving even lower doses

Experiment to determine limits of tolerance for fumonisin B1 in weaned piglets.

Three sows were fed a diet mixed with Fusarium moniliforme fungal culture from the 107th day of pregnancy until parturition. Fumonisin B 1 toxin was administered to two sows (sows 1 and 2) in a daily dose of 300 mg for an additional 7 days subsequent to parturition, i.e., for a total of 14-16 days. The third sow (No. 3) was given the toxin in the same daily dose only until parturition, i.e., for 7 days in total. There were no symptoms observed in any of the sows. Two piglets were taken from each of the three sows and sacrificed immediately after parturition, i.e., prior to the first suckling. After 24 h, two additional piglets were taken for slaughter from each of the litters, which by then had access to colostrum. Finally, on the 7th day postparturition another two piglets per litter were sacrificed and material obtained from them was processed for examination. It was established that fumonisin B 1 present in the Fusarium moniliforme culture resulted in damage to the fetuses in utero. Of the changes indicating toxic effect, intraalveolar, subpleural, and interstitial pulmonary edema of various degrees of severity could be detected in the piglets sacrificed immediately following parturition and before the first suckling. Pathological changes were observed in the histopathological sections of the liver, and increases in the activities of plasma aspartic acid transaminase (AST), gamma glutamyl transferase (GGT) and alkaline phosphatase (AKLP), higher than physiological levels were detected. The serum-free sphinganine/sphingosine ratio, considered a bioindicator of fumonisin B 1 toxicosis, varied in accordance with the degree of severity of the changes which occurred. The values obtained were found to be between 0.29 and 0.36 in the cases of severe pulmonary edema, and between 0.20 and 0.24 for the cases of mild pulmonary edema. In the piglets of the sows fed the toxin for an additional 7 days subsequent to parturition and which were born with severe pulmonary edema, mild pulmonary edema could be detected after colostrum suckling, 24 h, and 7 days after parturition. The SA/SO value of the serum in these two piglets was 0.19 and 0.20, while at the same time AST, GGT, and ALKP values higher than physiological levels were measured. In the milk samples taken from sows 1 and 2 and examined after 24 h and after 7 days FB 1 was detected in quantities of 18.0-27.5 ppb. There were no changes observed on the seventh day in the piglets of the third sow, the diet of which contained no toxin after parturition. However, as the piglets of the third sow demonstrated only mild effects of pulmonary edema it is not possible to establish with certainty a postpartum cause-effect relationship between fumonisin in colostrum and pulmonary edema.

F. Vetési

Papers

Experiment to determine limits of tolerance for fumonisin B1 in weaned piglets.

Preliminary communication: Examination of the harmful effect to fetuses of fumonisin B1 in pregnant sows