Mycotoxins are the most frequently occurring natural contaminants in human and animal diet. Among them, deoxynivalenol (DON), produced by Fusarium, is one of the most prevalent and thus represents an important health risk. Recent detection methods revealed new mycotoxins and new molecules derivated from the “native” mycotoxins. The main derivates of DON are the acetylated forms produced by the fungi (3- and 15-acetyl-DON), the biologically “modified” forms produced by the plant (deoxynivalenol-3-β-d-glucopyranoside), or after bacteria transformation (de-epoxy DON, 3-epi-DON and 3-keto-DON) as well as the chemically “modified” forms (norDON A-C and DON-sulfonates). High proportions of acetylated and modified forms of DON co-occur with DON, increasing the exposure and the health risk. DON and its acetylated and modified forms are rapidly absorbed following ingestion. At the molecular level, DON binds to the ribosome, induces a ribotoxic stress leading to the activation of MAP kinases, cellular cell-cycle arrest and apoptosis. The toxic effects of DON include emesis and anorexia, alteration of intestinal and immune functions, reduced absorption of the nutrients as well as increased susceptibility to infection and chronic diseases. In contrast to DON, very little information exists concerning the acetylated and modified forms; some can be converted back to DON, their ability to bind to the ribosome and to induce cellular effects varies according to the toxin. Except for the acetylated forms, their toxicity and impact on human and animal health are poorly documented.

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Toxicology of deoxynivalenol and its acetylated and modified forms

EFSA was asked to deliver a scientific opinion on the risks to public health related to the presence of aflatoxins in food. The risk assessment was confined to aflatoxin B1 (AFB1), AFB2, AFG1, AFG2 and AFM1. More than 200,000 analytical results on the occurrence of aflatoxins were used in the evaluation. Grains and grain-based products made the largest contribution to the mean chronic dietary exposure to AFB1 in all age classes, while 'liquid milk' and 'fermented milk products' were the main contributors to the AFM1 mean exposure. Aflatoxins are genotoxic and AFB1 can cause hepatocellular carcinomas (HCCs) in humans. The CONTAM Panel selected a benchmark dose lower confidence limit (BMDL) for a benchmark response of 10% of 0.4 μg/kg body weight (bw) per day for the incidence of HCC in male rats following AFB1 exposure to be used in a margin of exposure (MOE) approach. The calculation of a BMDL from the human data was not appropriate; instead, the cancer potencies estimated by the Joint FAO/WHO Expert Committee on Food Additives in 2016 were used. For AFM1, a potency factor of 0.1 relative to AFB1 was used. For AFG1, AFB2 and AFG2, the in vivo data are not sufficient to derive potency factors and equal potency to AFB1 was assumed as in previous assessments. MOE values for AFB1 exposure ranged from 5,000 to 29 and for AFM1 from 100,000 to 508. The calculated MOEs are below 10,000 for AFB1 and also for AFM1 where some surveys, particularly for the younger age groups, have an MOE below 10,000. This raises a health concern. The estimated cancer risks in humans following exposure to AFB1 and AFM1 are in-line with the conclusion drawn from the MOEs. The conclusions also apply to the combined exposure to all five aflatoxins.

Risk assessment of aflatoxins in food

METASTATIC ABSCESSES and metastatic tumors can appear in locations that do not seem to be in line of direct spread from their primary focus. There is even a regularity of distribution of these paradoxic metastases. Empirically, the roentgenologist makes a diagnosis of primary carcinoma of the prostate when he finds a certain peculiar distribution of bone lesions in the pelvis. Adequate explanation has not been forthcoming for. the typical and peculiar distribution of these metastatic lesions. The pattern, to me, is not at all that of the nerve sheaths of the area as suggested by Warren, et al.1 It is not the pattern of lymph vessel distribution. The only anatomic system into which this pattern fits is the system of veins which, in its plexiform ramifications, infiltrates and invests the sacrum, the lumbar spine, and the adjacent wings of the ilia. Several years ago, I suggested that the architecture of this plexus of veins could be explored by taking advantage of the pelvic anastomoses of the deep dorsal vein of the penis. The connections and the collateral circulations of this vein are identical with those of the prostatic plexus of veins with which it connects. Valves in the veins of this region are exceedingly variable. All valves present permit flow toward the sacral venous plexus. Injections were first made in I937. A preliminary report was read before the Conference of Eastern Radiologists, in Philadelphia, January 29, I938, under the title of \"The Veins of the Sacrum in Relation to Metastatic Carcinoma from the Prostate.\" This work has been continued and extended. Injections and corrosion preparations of the vessels of the head and neck, already completed, formed an invaluable background for this study. The dissemination of infections and tumors from organs in other regions by the veins about the spine has also been considered. This has led to a better appreciation of the role of the vertebral veins in normal physiology.

The function of the vertebral veins and their role in the spread of metastases : Skeletal cancer metastasis recent expansion of orthopaedic expertise

Mycotoxins are known worldwide as fungus-produced toxins that adulterate a wide heterogeneity of raw feed ingredients and final products. Consumption of mycotoxins-contaminated feed causes a plethora of harmful responses from acute toxicity to many persistent health disorders with lethal outcomes; such as mycotoxicosis when ingested by animals. Therefore, the main task for feed producers is to minimize the concentration of mycotoxin by applying different strategies aimed at minimizing the risk of mycotoxin effects on animals and human health. Once mycotoxins enter the production chain it is hard to eliminate or inactivate them. This paper examines the most recent findings on different processes and strategies for the reduction of toxicity of mycotoxins in animals. The review gives detailed information about the decontamination approaches to mitigate mycotoxin contamination of feedstuffs and compound feed, which could be implemented in practice.

Decontamination of Mycotoxin-Contaminated Feedstuffs and Compound Feed.

An increasing number of human beings from developed countries are colonized by Escherichia coli strains producing colibactin, a genotoxin suspected to be associated with the development of colorectal cancers. Deoxynivalenol (DON) is the most prevalent mycotoxin that contaminates staple food—especially cereal products—in Europe and North America. This study investigates the effect of the food contaminant DON on the genotoxicity of the E. coli strains producing colibactin. In vitro, intestinal epithelial cells were coexposed to DON and E. coli producing colibactin. In vivo, newborn rats colonized at birth with E. coli producing colibactin were fed a DON-contaminated diet. Intestinal DNA damage was estimated by the phosphorylation of histone H2AX. DON exacerbates the genotoxicity of the E. coli producing colibactin in a time- and dose-dependent manner in vitro. Although DON had no effect on the composition of the gut microbiota, and especially on the number of E. coli, a significant increase in DNA damage was observed in intestinal epithelial cells of animals colonized by E. coli strains producing colibactin and coexposed to DON compared to animals colonized with E. coli strains unable to produce colibactin or animals exposed only to DON. In conclusion, our data demonstrate that the genotoxicity of E. coli strains producing colibactin, increasingly present in the microbiota of asymptomatic human beings, is modulated by the presence of DON in the diet. This raises questions about the synergism between food contaminants and gut microbiota with regard to intestinal carcinogenesis. IMPORTANCE An increasing number of human beings from developed countries are colonized by Escherichia coli strains producing colibactin, a genotoxin suspected to be associated with the development of colorectal cancers. Deoxynivalenol (DON) is the most prevalent mycotoxin that contaminates staple food—especially cereal products—in Europe and North America. Our in vitro and in vivo results demonstrate that the intestinal DNA damage induced by colibactin-producing E. coli strains was exacerbated by the presence of DON in the diet. This raises questions about the synergism between food contaminants and gut microbiota with regard to intestinal carcinogenesis.

https://mbio.asm.org/content/mbio/8/2/e00007-17.full.pdf

The Food Contaminant Deoxynivalenol Exacerbates the Genotoxicity of Gut Microbiota

Mycotoxins are the most common contaminants of food and feed worldwide and are considered an important risk factor for human and animal health. Oxidative stress occurs in cells when the concentration of reactive oxygen species exceeds the cell’s antioxidant capacity. Oxidative stress causes DNA damage, enhances lipid peroxidation, protein damage and cell death. This review addresses the toxicity of the major mycotoxins, especially aflatoxin B1, deoxynivalenol, nivalenol, T-2 toxin, fumonisin B1, ochratoxin, patulin and zearalenone, in relation to oxidative stress. It summarises the data associated with oxidative stress as a plausible mechanism for mycotoxin-induced toxicity. Given the contamination caused by mycotoxins worldwide, the protective effects of a variety of natural compounds due to their antioxidant capacities have been evaluated. We review data on the ability of vitamins, flavonoids, crocin, curcumin, green tea, lycopene, phytic acid, L-carnitine, melatonin, minerals and mixtures of anti-oxida...

Mycotoxins and oxidative stress: where are we?

Deoxynivalenol (DON) is one of the most prevalent type B trichothecenes present in food inducing adverse effects, including intestinal changes and immunosuppression. The aim of the present study was to investigate the effects of DON on rats exposed for 7, 14 and 28 days to mycotoxin-contaminated diets, using histological and immunohistochemical analyses on liver and lymphoid organs. Fifty rats received a control diet, or a diet contaminated with 1.75 mg/kg of DON for 30 days, or a diet contaminated with 11.4 mg/kg of DON for 7, 14 or 30 days. Ingestion of contaminated feed induced a significant increase in the lesional score in the liver, spleen, and lymph nodes. The main histological findings observed in the liver were cytoplasmic vacuolisation and hepatocelular megalocytosis. A significant increase in hepatocyte proliferation was observed in rats that received 1.75 mg/kg of DON. Lymphoid depletion was the main histological alteration observed in lymphoid organs, resulting in a significant increase in th...

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Deoxynivalenol in the liver and lymphoid organs of rats: effects of dose and duration on immunohistological changes

Malignant Pilomatricoma in a Dog

Occurrence of mycotoxins in agricultural products represents a risk for human and animal health. Therefore, there is a requirement of strategies to mitigate their harmful impacts. This study invest...

Phytic acid modulates the morphology, immunological response of cytokines and β-defensins in porcine intestine exposed to deoxynivalenol and fumonisin B1

E.O. da Silva

Papers

Mycotoxins and oxidative stress: where are we?

Deoxynivalenol in the liver and lymphoid organs of rats: effects of dose and duration on immunohistological changes

Malignant Pilomatricoma in a Dog

Phytic acid modulates the morphology, immunological response of cytokines and β-defensins in porcine intestine exposed to deoxynivalenol and fumonisin B1