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In vivo formation of N-acyl-fumonisin B1.

ABSTRACT: Fumonisins are fungal toxins found in corn and in corn-based foods. Fumonisin B1 (FB1) is the most common and is toxic to animals, causes cancer in rodents, and is a suspected risk factor for cancer and birth defects in humans. The hydrolyzed form of FB1 (HFB1) also occurs in foods and is metabolized by rats to compounds collectively known as N-acyl-HFB1 (also known as N-acyl-AP1). N-acyl-HFB1 is structurally similar to ceramides, metabolites which have important structural and signaling functions in cells. FB1 is N-acylated in vitro to ceramide-like metabolites which, like FB1, are cytotoxic. However, metabolism of FB1 and inhibition of ceramide synthase by its metabolites in vivo has not been demonstrated. Male rats were dosed ip with 0.5, 1, or 2 mg/kg body weight FB1 on five consecutive days and the liver and kidney thereafter processed for chemical analysis. N-acyl derivatives of fumonisin B1 were identified for the first time in these principal target organs of FB1 in rats, at levels up to 0.4 nmol/g tissue using mass spectrometry. The N-acyl chain length of the metabolites varied in a tissue-dependent manner with C16 derivatives predominating in the kidney and C24 derivatives being prevalent in the liver. The toxicological significance of N-acyl-fumonisins is not known and warrants investigation.

SUBMITTER: Harrer H

PROVIDER: S-EPMC4298654 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Occurrence and Probabilistic Risk Assessment of Fumonisin B1, Fumonisin B2 and Deoxynivalenol in Nixtamalized Maize in Mexico City.

Project description:Fumonisins (FB1+FB2) and deoxynivalenol (DON) are mycotoxins produced by Fusarium species that might be present in maize and maize products. Knowledge on their occurrence in nixtamalized maize from Mexico together with an accompanying risk assessment are scarce, while nixtamalized maize is an important food in Mexico. This study presents the occurrence of FB1 + FB2 and DON in nixtamalized maize samples collected in Mexico City and analyses their distribution and resulting estimated daily intake for Mexican consumers by a probabilistic approach using a two-dimensional Monte-Carlo simulation. The results obtained reveal that for FB1 + FB2, 47% of the Mexican men and 30% of the Mexican women might exceed the provisional tolerable daily intake (PMTDI) of 2 µg/kg bw/day for fumonisins and for DON, 9% of men and 5% of women would be exceeding the PMTDI of 1 µg/kg bw/day, corresponding to the high consumers. The results raise a flag for risk managers in Mexico, to consider regulations and interventions that lower mycotoxin levels in nixtamalized maize for human consumption.

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Project description:The purpose of the present study was to investigate the effects of phytic acid (IP6) on morphological and immunohistochemical parameters on intestinal explants exposed to deoxynivalenol (DON) and fumonisin B1 (FB1). The jejunal explants were exposed for 4 h to different treatments: control, DON (10 ?M), DON plus 2.5 mM or 5 mM IP6, FB1 (70 ?M), and FB1 plus 2.5 mM or 5 mM IP6. Both mycotoxins induced significant intestinal lesions and decreased villi height. The presence of 2.5 mM and 5 mM IP6 significantly inhibited the morphological changes caused by the mycotoxins. DON induced a significant increase in caspase-3 (83%) and cyclooxygenase-2 (71.3%) expression compared with the control. The presence of 5 mM IP6 induced a significant decrease in caspase-3 (43.7%) and Cox-2 (48%) expression compared with the DON group. FB1 induced a significant increase in caspase-3 expression (47%) compared to the control, whereas IP6 induced no significant change in this expression. A significant decrease in cell proliferation was observed when explants were exposed to 5 mM of IP6 in comparison with the DON and FB1 groups. The present data provide evidence that phytic acid modulates the toxic effects induced by DON and FB1 on intestinal tissue.

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Effect of Fumonisin B1 on Proliferation and Apoptosis of Intestinal Porcine Epithelial Cells.

Project description:Fumonisin B1 (FB1), which is a mycotoxin produced by Fusarium moniliforme and Fusarium rotarum, has a number of toxic effects in animals. Moldy feed containing FB1 can damage the intestine. In this study, we used intestinal porcine epithelial cells (IPEC-J2) as an in vitro model to explore the effects of FB1 on cell cycle and apoptosis. The results showed that IPEC-J2 cells treated with 10, 20, and 40 μg/mL FB1 for 48 h experienced different degrees of damage manifested as decreases in cell number and viability, as well as cell shrinkage and floating. In addition, FB1 reduced cell proliferation and the mRNA and protein expression of proliferating cell nuclear antigen (PCNA), cyclin-dependent kinase 2 (CDK2), CDK4, cyclinD1, and cyclinE1. FB1 blocked the cell cycle in the G1 phase. FB1 also induced mitochondrial pathway apoptosis, reduced mitochondrial membrane potential, and promoted mRNA and protein expression of Caspase3, Caspase9, and Bax. The findings suggest that FB1 can induce IPEC-J2 cell damage, block the cell cycle, and promote cell apoptosis.

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Microbial Reduction of Fumonisin B1 by the New Isolate Serratia marcescens 329-2.

Project description:The mycotoxin fumonisin (FB) has become a major problem in maize products in southeastern Asia. Fumonisin can affect the health of humans and many animals. Fumonisin contamination can be reduced by detoxifying microbial enzyme. Screening of 95 potent natural sources resulted in 5.3% of samples yielding a total of five bacterial isolates that were a promising solution, reducing approximately 10.0-30.0% of fumonisin B1 (FB1). Serratia marcescens, one of the dominant degrading bacteria, was identified with Gram staining, 16S rRNA gene, and MALDI-TOF/TOF MS. Cell-free extract showed the highest fumonisin reduction rates, 30.3% in solution and 37.0% in maize. Crude proteins from bacterial cells were analyzed with a label-free quantification technique. The results showed that hydrolase enzymes and transferase enzymes that can cooperate in the fumonisin degradation process were highly expressed in comparison to their levels in a control. These studies have shown that S. marcescens 329-2 is a new potential bacterium for FB1 reduction, and the production of FB1-reducing enzymes should be further explored.

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The kinetics of urinary fumonisin B1 excretion in humans consuming maize-based diets.

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| S-EPMC3820424 | biostudies-literature

Fumonisin B1: A Tool for Exploring the Multiple Functions of Sphingolipids in Plants.

Project description:Fumonisin toxins are produced by Fusarium fungal pathogens. Fumonisins are structural analogs of sphingosine and potent inhibitors of ceramide synthases (CerSs); they disrupt sphingolipid metabolism and cause disease in plants and animals. Over the past three decades, researchers have used fumonisin B1 (FB1), the most common fumonisin, as a probe to investigate sphingolipid metabolism in yeast and animals. Although the physiological effects of FB1 in plants have yet to be investigated in detail, forward and reverse genetic approaches have revealed many genes involved in these processes. In this review, we discuss the intricate network of signaling pathways affected by FB1, including changes in sphingolipid metabolism and the effects of these changes, with a focus on our current understanding of the multiple effects of FB1 on plant cell death and plant growth. We analyze the major findings that highlight the connections between sphingolipid metabolism and FB1-induced signaling, and we point out where additional research is needed to fill the gaps in our understanding of FB1-induced signaling pathways in plants.

| S-EPMC7652989 | biostudies-literature

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