The aflatoxin producing fungi, Aspergillus spp., are widely spread in nature and have severely contaminated food supplies of humans and animals, resulting in health hazards and even death. Therefore, there is great demand for aflatoxins research to develop suitable methods for their quantification, precise detection and control to ensure the safety of consumers’ health. Here, the chemistry and biosynthesis of the mycotoxins is discussed their occurrence and the health hazards to humans and livestock. This review focuses on resources, production, detection and control measures of aflatoxins to ensure food and feed safety. The results presented herein will facilitate health-conscious consumers and for experts, while providing knowledge on new and innovative approaches to ensure food safety and meet the future demands of the increasing population by decreasing the incidence of outbreaks by aflatoxins.

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Aflatoxins: A Global Concern for Food Safety, Human Health and Their Management

In mammals, cadmium is widely considered as a non-genotoxic carcinogen acting through a methylation-dependent epigenetic mechanism. Here, the effects of Cd treatment on the DNA methylation patten are examined together with its effect on chromatin reconfiguration in Posidonia oceanica. DNA methylation level and pattern were analysed in actively growing organs, under short- (6 h) and long- (2 d or 4 d) term and low (10 mM) and high (50 mM) doses of Cd, through a Methylation-Sensitive Amplification Polymorphism technique and an immunocytological approach, respectively. The expression of one member of the CHROMOMETHYLASE (CMT) family, a DNA methyltransferase, was also assessed by qRT-PCR. Nuclear chromatin ultrastructure was investigated by transmission electron microscopy. Cd treatment induced a DNA hypermethylation, as well as an up-regulation of CMT, indicating that de novo methylation did indeed occur. Moreover, a high dose of Cd led to a progressive heterochromatinization of interphase nuclei and apoptotic figures were also observed after long-term treatment. The data demonstrate that Cd perturbs the DNA methylation status through the involvement of a specific methyltransferase. Such changes are linked to nuclear chromatin reconfiguration likely to establish a new balance of expressed/repressed chromatin. Overall, the data show an epigenetic basis to the mechanism underlying Cd toxicity in plants.

/pdf/in-posidonia-oceanica-cadmium-induces-changes-in-dna-3cu7uj83mr.pdf

In Posidonia oceanica cadmium induces changes in DNA methylation and chromatin patterning

Mycotoxins are fungal metabolites commonly occurring in food, which pose a health risk to the consumer. Maximum levels for major mycotoxins allowed in food have been established worldwide. Good agricultural practices, plant disease management, and adequate storage conditions limit mycotoxin levels in the food chain yet do not eliminate mycotoxins completely. Food processing can further reduce mycotoxin levels by physical removal and decontamination by chemical or enzymatic transformation of mycotoxins into less toxic products. Physical removal of mycotoxins is very efficient: manual sorting of grains, nuts, and fruits by farmers as well as automatic sorting by the industry significantly lowers the mean mycotoxin content. Further processing such as milling, steeping, and extrusion can also reduce mycotoxin content. Mycotoxins can be detoxified chemically by reacting with food components and technical aids; these reactions are facilitated by high temperature and alkaline or acidic conditions. Detoxification of mycotoxins can also be achieved enzymatically. Some enzymes able to transform mycotoxins naturally occur in food commodities or are produced during fermentation but more efficient detoxification can be achieved by deliberate introduction of purified enzymes. We recommend integrating evaluation of processing technologies for their impact on mycotoxins into risk management. Processing steps proven to mitigate mycotoxin contamination should be used whenever necessary. Development of detoxification technologies for high-risk commodities should be a priority for research. While physical techniques currently offer the most efficient post-harvest reduction of mycotoxin content in food, biotechnology possesses the largest potential for future developments.

/pdf/impact-of-food-processing-and-detoxification-treatments-on-2974len175.pdf

Impact of food processing and detoxification treatments on mycotoxin contamination.

Spirulina is a species of filamentous cyanobacteria that has long been used as a food supplement. In particular, Spirulina platensis and Spirulina maxima are the most important. Thanks to a high protein and vitamin content, Spirulina is used as a nutraceutical food supplement, although its other potential health benefits have attracted much attention. Oxidative stress and dysfunctional immunity cause many diseases in humans, including atherosclerosis, cardiac hypertrophy, heart failure, and hypertension. Thus, the antioxidant, immunomodulatory, and anti-inflammatory activities of these microalgae may play an important role in human health. Here, we discuss the antioxidant, immunomodulatory, and anti-inflammatory activities of Spirulina in both animals and humans, along with the underlying mechanisms. In addition, its commercial and regulatory status in different countries is discussed as well. Spirulina activates cellular antioxidant enzymes, inhibits lipid peroxidation and DNA damage, scavenges free radicals, and increases the activity of superoxide dismutase and catalase. Notably, there appears to be a threshold level above which Spirulina will taper off the antioxidant activity. Clinical trials show that Spirulina prevents skeletal muscle damage under conditions of exercise-induced oxidative stress and can stimulate the production of antibodies and up- or downregulate the expression of cytokine-encoding genes to induce immunomodulatory and anti-inflammatory responses. The molecular mechanism(s) by which Spirulina induces these activities is unclear, but phycocyanin and β-carotene are important molecules. Moreover, Spirulina effectively regulates the ERK1/2, JNK, p38, and IκB pathways. This review provides new insight into the potential therapeutic applications of Spirulina and may provide new ideas for future studies.

The antioxidant, immunomodulatory, and anti-inflammatory activities of Spirulina: an overview

Since ochratoxin A (OTA) was discovered, it has been ubiquitous as a natural contaminant of moldy food and feed. The multiple toxic effects of OTA are a real threat for human beings and animal health. For example, OTA can cause porcine nephropathy but can also damage poultries. Humans exposed to OTA can develop (notably by inhalation in the development of acute renal failure within 24 h) a range of chronic disorders such as upper urothelial carcinoma. OTA plays the main role in the pathogenesis of some renal diseases including Balkan endemic nephropathy, kidney tumors occurring in certain endemic regions of the Balkan Peninsula, and chronic interstitial nephropathy occurring in Northern African countries and likely in other parts of the world. OTA leads to DNA adduct formation, which is known for its genotoxicity and carcinogenicity. The present article discusses how renal carcinogenicity and nephrotoxicity cause both oxidative stress and direct genotoxicity. Careful analyses of the data show that OTA carcinogenic effects are due to combined direct and indirect mechanisms (e.g., genotoxicity, oxidative stress, epigenetic factors). Altogether this provides strong evidence that OTA carcinogenicity can also occur in humans.

https://www.mdpi.com/2072-6651/8/7/191/pdf

Ochratoxin A: 50 Years of Research

Aflatoxins are cancerogenic compounds produced predominantly by certain strains of the Aspergillus genus. The ideal solution for minimization of health risk that aflatoxins pose is the prevention of foods and feeds contamination. Unfortunately, these contaminants can never be completely removed, and on that account, many studies have been carried out to explore an effective process of their detoxification to a threshold level. Biological decontamination seems to be attractive because it works under mild, environmentally friendly conditions. This review is focused on the biological detoxification of aflatoxins, especially aflatoxin B1, by microorganisms. There are briefly mentioned aflatoxin metabolic pathways in the human and animal body. Microorganisms such as soil or water bacteria, fungi, and protozoa and specific enzymes isolated from microbial systems can degrade aflatoxin group members with varied efficiency to less- or nontoxic products. Some aflatoxin-producing fungi from Aspergillus species have ...

Biological degradation of aflatoxins

Trichothecenes are a group of mycotoxins mainly produced by the fungi of Fusarium genus. Consumers are particularly concerned over the toxicity and food safety of trichothecenes and their metabolites from food-producing animals. The metabolism of T-2 toxin, deoxynivalenol (DON), nivalenol (NIV), fusarenon-X (FX), diacetoxyscirpenol (DAS), 3-acetyldeoxy-nivalenol (3-aDON), and 15-acetyldeoxynivalenol (15-aDON) in rodents, swine, ruminants, poultry, and humans are reviewed in this article. Metabolic pathways of these mycotoxins are very different. The major metabolic pathways of T-2 toxin in animals are hydrolysis, hydroxylation, de-epoxidation, and conjugation. After being transformed to HT-2 toxin, it undergoes further hydroxylation at C-3' to yield 3'-hydroxy-HT-2 toxin, which is considered as an activation pathway, whereas transformation from T-2 to T-2 tetraol is an inactivation pathway in animals. The typical metabolites of T-2 toxin in animals are HT-2 toxin, T-2 triol, T-2 tetraol, neosolaniol (NEO), 3'-hydroxy-HT-2, and 3'-hydroxy-T-2, whereas HT-2 toxin is the main metabolite in humans. De-epoxidation is an important pathway for detoxification in animals. De-epoxy products, DOM-1, and de-epoxy-NIV are the main metabolites of DON and NIV in most animals, respectively. However, the two metabolites are not found in humans. Deacetyl can occur rapidly on the acetyl derivatives, 3-aDON, 15-aDON, and FX. DAS is metabolized in animals to 15-monoacetoxyscirpenol (15-MAS) via C-4 deacetylation and then transformed to scirpentriol (SCP) via C-15 deacetylation. Finally, the epoxy is lost, yielding de-epoxy-SCP. De-epoxy-15-MAS is also the main metabolite of DAS. 15-MAS is the main metabolite in human skin. The review on the metabolism of trichothecenes will help one to well understand the fate of these toxins' future in animals and humans, as well as provide basic information for the risk assessment of them for food safety.

Metabolic pathways of trichothecenes.

Ochratoxin A (OTA) as a carcinogenic of group 2B to humans is produced by various fungi strains as Aspergillus and Penicillium. It is one of the most common contaminant in foodstuff. OTA is nephrotoxic, hepatotoxic, teratogenic, and immunotoxic and is assumed to cause Balkan Endemic Nephropathy (BEN), a chronic kidney disease in humans when it is digested in combination with mycotoxin citrinin. The metabolism affects greatly the fates and the toxicity of a mycotoxins in humans, animals, and plants. The understanding of the metabolism of mycotoxins by the organism as fungi, yeast, bacteria and enzymes would be very helpful for the control of the contamination by the mycotoxins in foods and feeds, and understanding of the biotransformation of the mycotoxin in the body of humans, animals, plants, microorganisms would be beneficial to the risk assessment of food safety. In animals and humans, OTA can be metabolized in the kidney, liver and intestines. Hydrolysis, hydroxylation, lactone-opening and conjugation are the major metabolic pathways. OTalpha (OTα) formed by the cleavage of the peptidic bond in OTA is a major metabolite not only in animals and humans, but also in microorganisms and enzyme systems. It is considered as a nontoxic product. However, the lactone-opened product (OP-OTA), found in rodents, is higher toxic than its parent, OTA.. (4R)-4-OH-OTA is the major hydroxy product in rodents, whereas the 4S isomer is the major in pigs. 10-OH-OTA is currently found only in rabbits. Furthermore, OTA can lose the chlorine on C-5 to produce ochratoxin B (OTB), and OTB is further to 4-OH-OTB and ochratoxin β (OTβ). Ochratoxin quinine/hydroquinone (OTQ/OTHQ) is the metabolite of OTA in animals. In addition, the conjugates of OTA such as hexose and pentose conjugates can be found in animals. Such more polar metabolites make OTA to eliminate faster. Currently, a debate exits on the formation of OTA-DNA adducts. Plants can metabolize OTA as well. OH-OTA methyl ester and OH-OTA-β-glucoside are formed in many plants besides OTα and OH-OTA. OTA can be biotransformed into OTα by some yeast strains. Fungi can produce some of the same metabolites as animals. OTα, OTβ, 4-R-OH-OTA, 4-R-OH-OTB, and 10-OH-OTA are the metabolites in fungi. Several commercial enzymes are able to biodegrade OTA into the nontoxic OTα efficiently. This review on the metabolism of OTA helps to well understand the fate of OTA in different organisms, as well as provides very crucial information for toxicology and food safety assessments on human health.

Metabolic pathways of ochratoxin A.

Trichothecenes comprise a large family of structurally related toxins mainly produced by fungi belonging to the genusFusarium. Among trichothecenes, type A and type B are of the most concern due to their broad and highly toxic nature. In order to addressstructure-activity relationships (SAR) of trichothecenes, relationships between structural features and biological effects of trichothecenemycotoxins in mammalian systems are summarized in this paper. The double bond between C-9-C-10 and the 12,13-epoxide ringare essential structural features for trichothecene toxicity. Removal of these groups results in a complete loss of toxicity. A hydroxylgroup at C-3 enhances trichothecene toxicity, while this activity decreases gradually when C-3 is substituted with either hydrogen or anacetoxy group. The presence of a hydroxyl group at C-4 promotes slightly lower toxicity than an acetoxy group at the same position. Thetoxicity for type B trichothecenes decreases if the substituent at C-4 is changed from acetoxy to hydroxyl or hydrogen at C-4 position.The presence of hydroxyl and hydrogen groups on C-15 decreases the trichothecene toxicity in comparison with an acetoxy group attachedto this carbon. Trichothecenes toxicity increases when a macrocyclic ring exists between the C-4 and C-15. At C-8 position, anoxygenated substitution at C-8 is essential for trichothecene toxicity, indicating a decrease in the toxicity if substituent change fromisovaleryloxy through hydrogen to the hydroxyl group. The presence of a second epoxy ring at C-7-C-8 reduces the toxicity, whereas epoxidationat C-9-C-10 of some macrocyclic trichothecenes increases the activity. Conjugated trichothecenes could release their toxic precursorsafter hydrolysis in animals, and present an additional potential risk. The SAR study of trichothecenes should provide some crucialinformation for a better understanding of trichothecene chemical and biological properties in food contamination.

Trichothecenes: Structure-Toxic Activity Relationships

Dispositions of deoxynivalenol (DON) in rats and chickens were investigated, using a radiotracer method coupled with a novel γ-accurate radioisotope counting (γ-ARC) radio-high-performance liquid chromatography ion trap time-of-flight tandem mass spectrometry (radio-HPLC-IT-TOF-MS/MS) system. 3β-(3)H-DON was chemically synthesized and orally administrated to both sexes of rats and chickens as single or multiple doses. The results showed that DON was widely distributed and quickly eliminated in all tissues. The highest concentration was found in the gastrointestinal tract at 6 h post-administration. Substantially lower levels were detected in the kidney, liver, heart, lung, spleen, and brain. Three new metabolites were identified tentatively as 10-deoxynivalenol-sulfonate, 10-deepoxy-deoxynivalenol (DOM-1)-sulfonate, and deoxynivalenol-3α-sulfate. Deoxynivalenol-3α-sulfate was a major metabolite in chickens, while the major forms in rats were DOM-1 and DON. Additionally, a higher excretion rate in urine was observed in female rats than in male rats. The differences in metabolite profiles and excretion rates, which suggested diverse ways to detoxify, may relate to the different tolerances in different genders or species.

Metabolism, distribution, and excretion of deoxynivalenol with combined techniques of radiotracing, high-performance liquid chromatography ion trap time-of-flight mass spectrometry, and online radiometric detection.

Qinghua Wu

Papers

Biological degradation of aflatoxins

Metabolic pathways of trichothecenes.

Metabolic pathways of ochratoxin A.

Trichothecenes: Structure-Toxic Activity Relationships

Metabolism, distribution, and excretion of deoxynivalenol with combined techniques of radiotracing, high-performance liquid chromatography ion trap time-of-flight mass spectrometry, and online radiometric detection.