Alterations in Daphnia magna exposed to enniatin B and beauvericin provide additional value as environmental indicators.

Mycotoxins beauvericin (BEA) and enniatin B (ENN B) affect negatively several systems and demand more studies as the mechanisms are still unclear. The simultaneous presence of contaminants in the environment manifests consequences of exposure for both animals and flora. Daphnia magna is considered an ideal invertebrate to detect effects of toxic compounds and environmental alterations. In this study, the potential toxicity and the basic mechanism of BEA and ENN B individually and combined were studied in D. magna. Acute and delayed toxicity were evaluated, and transcript levels of genes involved in xenobiotic metabolism (mox, gst, abcb1, and abcc5), reproduction, and oxidative stress (vtg-SOD) were analyzed by qPCR. Though no acute toxicity was found, results revealed a spinning around and circular profile of swimming, a strong decrease of survival after 72 h for BEA and ENN B at 16 µM and 6.25 µM, respectively, while for BEA + ENN B [8 + 1.6] µM after 96 h. The amount of mycotoxin remaining in the media revealed that the higher the concentration assayed the higher the amount remaining in the media. Differential regulation of genes suggests that xenobiotic metabolism is affected denoting different effects on transcription for tested mycotoxins. The results provide new insights into the underlying risk assessment of BEA and ENN B not only through food for consumers but also for the environment.

Emerging contaminants and priority substances in marine sediments from Cartagena Bay and the Grand Marsh of Santa Marta (Ramsar site), Colombia.

Emerging pollutants and priority substances are of growing concern due to their toxicity potential to aquatic organisms and human health. However, few reports on this issue in marine ecosystems in general and, more specifically, on the Colombian Caribbean coast are available. The aim of this study was to detect these compounds in sediments from Cartagena Bay (CB) and in the Grand Marsh of Santa Marta, GMSM (Ramsar site), in order to determine how they related to in vitro cytotoxicity assays on HepG2 cells of sediment extracts. A total of thirty compounds were detected using GC-MS/MS in fifteen stations during both the rainy and the dry seasons. Sediments from CB had a wide range of different toxicants, with polycyclic aromatic hydrocarbons (PAHs) being the most prevalent (12 PAHs, 5.5-881.6 ng/g). Total PCBs ranged from < LOD to 18.6 ng/g, with PCB 138 being the most common detected congener. Residues of p,p'-DDE, Chlorpyrifos and two organophosphate flame retardants, TEHP and ToTP, were found in most sampling locations. The UV filters 4MBC and homosalate were recurrently found in sediments, and the fragrance galaxolide appeared in all cases, with the greatest concentrations found on a touristic beach. In GMSM, with the exception of deltamethrin, all chemicals evaluated had lower average values than in CB. According to sediment quality guidelines, some sites in CB presented values of PAHs higher than the threshold effects level, while in the marsh, none of the stations exceeded it. HepG2 cells exposed to 1% sediment extracts presented reduced cell viability up to 26%. Cytotoxicity displayed a negative correlation with chlorpyrifos concentration. In short, these data suggest the bay and the marsh have specific contamination fingerprints related to anthropogenic interventions. This research highlights the need to further investigate the ecotoxicological implications of detected chemical stressors in these ecosystems.

Larval zebrafish as an in vitro model for evaluating toxicological effects of mycotoxins.

The presence of mycotoxins in food has created concern. Mycotoxin prevalence in our environment has changed in the last few years maybe due to climatic and other environmental changes. Evidence has emerged from in vitro and in vivo models: some mycotoxins have been found to be potentially carcinogenic, embryogenically harmful, teratogenic, and to generate nephrotoxicity. The risk assessment of exposures to mycotoxins at early life stages became mandatory. In this regard, the effects of toxic compounds on zebrafish have been widely studied, and more recently, mycotoxins have been tested with respect to their effects on developmental and teratogenic effects in this model system, which offers several advantages as it is an inexpensive and an accessible vertebrate model to study developmental toxicity. External post-fertilization and quick maturation make it sensitive to environmental effects and facilitate the detection of endpoints such as morphological deformities, time of hatching, and behavioral responses. Therefore, there is a potential for larval zebrafish to provide new insights into the toxicological effects of mycotoxins. We provide an overview of recent mycotoxin toxicological research in zebrafish embryos and larvae, highlighting its usefulness to toxicology and discuss the strengths and limitations of this model system.

Does low concentration mycotoxin exposure induce toxicity in HepG2 cells through oxidative stress?

The purpose of this study was to determine whether exposure to low concentrations of deoxynivalenol (DON), T-2 toxin (T-2) and patulin (PAT) in a human hepatocellular carcinoma cell line (HepG2) exerts toxic effects through mechanisms related to oxidative stress, and how cells deal with such exposure. Cell viability was determined by the MTT and protein content (PC) assays over 24, 48 and 72 h. The IC50 values detected ranged from >10 to 2.53 ± 0.21 µM (DON), 0.050 ± 0.025 to 0.034 ± 0.007 µM (T-2) and 2.66 ± 0.66 to 1.17 ± 0.21 µM (PAT). The key players in oxidative stress are the generation of reactive oxygen species (ROS), lipid peroxidation (LPO) and mitochondrial membrane potential (MMP) dysfunction. The results obtained showed that PAT, DON and T-2 did not significantly increase LPO or ROS production with respect to the controls. Moreover, PAT and DON did not alter MMP, though T-2 increased MMP at the higher concentrations tested (17 and 34 nM). In conclusion, the exposure of HepG2 cells to nontoxic concentrations of T-2 condition them against subsequent cellular oxidative conditions induced by even higher concentrations of mycotoxin.

Effect of Acrylamide and Mycotoxins in SH-SY5Y Cells: A Review.

Thermal processes induce the formation of undesired toxic components, such as acrylamide (AA), which has been shown to induce brain toxicity in humans and classified as Group 2A by the International Agency of Research in Cancer (IARC), as well as some mycotoxins. AA and mycotoxins' toxicity is studied in several in vitro models, including the neuroblastoma cell line model SH-SY5Y cells. Both AA and mycotoxins occur together in the same food matrix cereal base (bread, pasta, potatoes, coffee roasting, etc.). Therefore, the goal of this review is to deepen the knowledge about the neurological effects that AA and mycotoxins can induce on the in vitro model SH-SY5Y and its mechanism of action (MoA) focusing on the experimental assays reported in publications of the last 10 years. The analysis of the latest publications shows that most of them are focused on cytotoxicity, apoptosis, and alteration in protein expression, while others are interested in oxidative stress, axonopathy, and the disruption of neurite outgrowth. While both AA and mycotoxins have been studied in SH-SY5Y cells separately, the mixture of them is starting to draw the interest of the scientific community. This highlights a new and interesting field to explore due to the findings reported in several publications that can be compared and the implications in human health that both could cause. In relation to the assays used, the most employed were the MTT, axonopathy, and qPCR assays. The concentration dose range studied was 0.1-10 mM for AA and 2 fM to 200 µM depending on the toxicity and time of exposure for mycotoxins. A healthy and varied diet allows the incorporation of a large family of bioactive compounds that can mitigate the toxic effects associated with contaminants present in food. Although this has been reported in some publications for mycotoxins, there is still a big gap for AA which evidences that more investigations are needed to better explore the risks for human health when exposed to AA and mycotoxins.

Beauvericin and enniatin B mycotoxins alter aquatic ecosystems: Effects on green algae.

Myxotoxins can contaminate algal-based products and arrive to the food chain to consumers producing chronic toxicity effects. Here, we studied phytotoxicity of mycotoxins, beauvericin (BEA) and ennaitin B (ENN B) in four phytoplankton strains: Acutodesmus sp., Chlamydomonas reinhardtii, Haematococcus pluvialis, and Monoraphidium griffithii, which are all green algae. It was tested the capacity of clearing the media of BEA and ENN B at different concentrations by comparing nominal and measured quantifications. Results revealed that Acutodesmus sp. and C. reinhardtii tended to flow up and down growth rate without reaching values below 50% or 60%, respectively. On the other hand, for H. pluvialis and M. griffith, IC50 values were reached. Regarding the clearance of media, in individual treatment a decrease of the quantified mycotoxin between nominal and measured values was observed; while in binary treatment, differences among both values were higher and more noted for BEA than for ENN B.

Involvement of pro-inflammatory mediators and cell cycle disruption in neuronal cells induced by gliotoxin and ochratoxin A after individual and combined exposure.

Mycotoxins such as gliotoxin (GTX) and ochratoxin A (OTA) are secondary metabolites of Aspergillus and Penicillum found in food and feed. Both mycotoxins have shown to exert a detrimental effect on neuronal activity. The following study was carried out to elucidate the mechanisms by which GTX and OTA exert their toxicity. Non-differentiated SH-SY5Y neuronal-like cells were treated with GTX, OTA and their combinations to assess their cytotoxic effect using the MTT assay during 24, 48 and 72 h of exposure. Based on the results of the cytotoxic assays, cell cycle proliferation and immunological mediators were measured by determining the production of IL-6 and TNF-α using flow cytometry and ELISA, respectively. The IC50 values obtained were 1.24 and 1.35 µM when SH-SY5Y cells were treated with GTX at 48 h and 72 h, respectively. IC50 values of 8.25, 5.49 and 4.5 µM were obtained for OTA treatment at 24 h, 48 h and 72 h, respectively. The SubG0 phase increased in both treatments at 24 and 48 h. On the other hand, IL-6 and TNF-α production was increased in all mycotoxin treatments studied and was more pronounced for [GTX + OTA] after 48 h exposure. The additive and synergistic effect observed by the isobologram analysis between GTX and OTA resulted to a higher cytotoxicity which can be explained by the increased production of IL-6 and TNF-α inflammatory mediators that play an important role in the toxicity mechanism of these mycotoxins.

Study of cytotoxicity in neuroblastoma cell line exposed to patulin and citrinin.

Mycotoxins can be found in food and feed storage as well as in several kinds of foodstuff and are capable of harming mammals and some of them even in small doses. This study investigated on the undifferentiated neuronal cell line SH-SY5Y the effects of two mycotoxins: patulin (PAT) and citrinin (CTN), which are predominantly produced by fungi species Penicillium and Aspergillus. Here, the individual and combined cytotoxicity of PAT and CTN was investigated using the cytotoxic assay MTT. Our findings indicate that after 24 h of treatment, the IC50 value for PAT is 2.01 µM, which decreases at 1.5 µM after 48 h. In contrast, CTN did not attain an IC50 value at the tested concentration. Therefore, we found PAT to be the more toxic compared to CTN. However, the combined treatment suggests an additive toxic effect. With 2,7-dichlorodihydrofluorescin diacetate (DCFH-DA) DCFH-DA assay, ROS generation was demonstrated after CTN treatment, but PAT showed only small changes. The mixture presented a very constant behavior over time. Finally, the median-effect/combination index (CI-) isobologram equation demonstrated an additive effect after 24 h, but an antagonistic effect after 48 h for the interaction of the two mycotoxins.

Daphnia magna model for the study of mycotoxins present in food: Gliotoxin, ochratoxin A and its combination.

Mycotoxins are low molecular weight compounds present in food and feed. Although their effects on human health have been widely described, their mechanisms of action are still undefined. Gliotoxin (GTX) and ochratoxin A (OTA) are among the most dangerous mycotoxins produced by Aspergillus spp. Therefore, their toxicity was studied in the Daphnia magna model, which has high capacity to predict cytotoxicity and assess ecotoxicity, comparable to mammalian models. The study consisted of a series of tests to evaluate the effects of mycotoxins GTX, OTA and their combinations at different dilutions on Daphnia magna that were conducted according to standardized OECD 202 and 211 guidelines. The following assays were carried out: acute toxicity test, heartbeat, delayed toxicity test, reproduction, growth rate test. Reproducibility was determined by observing the offspring after 21 days of GTX exposure. In acute and delayed toxicity transcript levels of genes involved in xenobiotic metabolism (mox, gst, abcb1, and abcc5), and oxidative stress (vtg-SOD) were analyzed by qPCR. GTX showed acute toxicity and decreased heart rate in D. magna compared to OTA. On the other hand, OTA showed a delayed effect as evidenced by the immobility test. Both mycotoxins showed to increase genes involved in xenobiotic metabolism, while only the mycotoxin mixture increased oxidative stress. These results suggest that the mycotoxins tested could have negative impact on the environment and human health.

Individual and combined effect of acrylamide, fumitremorgin C and penitrem A on human neuroblastoma SH-SY5Y cells.

Acrylamide (AA) is a chemical compound that can be formed in certain foods during high-temperature cooking processes such as frying, baking, and roasting. Exposure to AA has been linked to several neurological effects, including peripheral neuropathy, ataxia, and impaired cognitive function. Penitrem A (PEN A) and Fumitremorgin C (FTC) are toxic mycotoxins produced by certain species of fungi, such as Penicillium Crustosum, Aspergillus Fumigatus and Neosartorya Fischeri. Both mycotoxins are commonly found in contaminated foods and animal feeds and have been linked to several adverse health effects in humans and animals, including the ability to disrupt normal functioning of the nervous system, tremors, seizures, muscle spasms, and convulsions. AA, PEN A, and FTC are all chemical contaminants. Understanding their toxicity and how they may affect human cells can help food safety authorities to establish safe exposure levels for these compounds through food and develop strategies to reduce their presence. The aim of this study was to explore the combined in vitro toxicological effects of AA, PEN A and FTC in SH-SY5Y cells. For this purpose, cells were treated with AA, FTC, and PEN A as an individual and combined treatment. The types of interactions were assessed by the isobologram analysis. The cell cycle was performed by flow cytometry. Additive effect in binary and tertiary combinations was the major effect according to isobologram graphics. Our results demonstrate that PEN A possessed the highest potential in disturbing cell cycle progression by disrupting cell density in G0/G1 phase.

Perception of Food Safety Associated with Entomophagy among Higher-Education Students: Exploring Insects as a Novel Food Source.

Edible insects can diversify diets, improve livelihoods, contribute to food and nutrition security, and have a smaller ecological impact. The European Union has categorized insects as novel food, and recently, in 2021 and 2022, two species, Tenebrio molitor and Acheta domesticus, were authorized for commercialization. The acceptance and perception of food risk derived from insect consumption vary depending on factors impacting insect consumption acceptability, including neophobic tendencies, gender differences, familiarity, and gastronomic perceptions. The aim of this work was to evaluate the perception and acceptance of edible insects by exploring these factors. This study was carried out on higher-education students from universities in Valencia (Spain). The students recognized insects' high nutritional value, particularly protein content, and had varying levels of knowledge about specific nutritional components. In terms of labeling and marketing, removing health and sustainability benefits from packaging can improve consumer responses. Most respondents prefer clear labeling of insect derivatives, quality certification seals, and complete information about insect content. Students consider marketing and knowledge to be significant influencers of insect consumption. In summary, this text highlights the multifaceted nature of insect consumption acceptability. These insights offer valuable perspectives on insect consumption dynamics.

Cell cycle and enzymatic activity alterations induced by ROS production in human neuroblastoma cells SH-SY5Y exposed to Fumonisin B1, Ochratoxin A and their combination.

The presence of mycotoxins such as Fumonisin B1(FB1) and Ochratoxin A (OTA) in food and feed has become a threat to human and animal health since they can produce several afflictions. Different mechanisms of action by which they exercise their cytotoxic activity have been attributed to them, including the production of reactive oxygen species (ROS). For this reason, a measurement of the production of ROS species, and an evaluation of the intrinsic cell enzymatic antioxidant activity, including glutathione peroxidase (GPx), glutathione transferase (GTS), and catalase (CAT) together with a cytotoxicity and cell cycle assay have been performed in undifferentiated SH-SY5Y cells exposed to FB1, OTA and [FB1 + OTA] after 24 h and 48 h. FB1 and OTA. Monitoring of intracellular ROS production was carried out by the H2-DCFDA probe; while spectrometry analysis of absorbances was used for measuring GPx, GST and CAT activity. Finally, cell proliferation and cell cycle distribution were studied by flow cytometry. When cells were treated with OTA, an increase in GPx and GST activity was observed compared to FB1 and [FB1 + OTA]; conversely, a decrease in CAT activity was observed when cells were exposed to OTA coinciding with the results observed for ROS measurement. Regarding the cell cycle, when cells were exposed to OTA, a decrease in G0/G1 was detected, revealing an arrest of cell division for SH-SY5Y cells at the concentrations studied.

Cytoprotective, Antiproliferative, and Anti-Oxidant Potential of the Hydroethanolic Extract of Fridericia chica Leaves on Human Cancer Cell Lines Exposed to α- and ß-Zearalenol.

Fridericia chica (Bignoniaceae) is a Colombian Caribbean plant with numerous health benefits, including properties such as wound healing, immune system stimulation, and antioxidant capacity, among others. Mycotoxins alpha-zearalenol (α-ZEL) and beta-zearalenol (ß-ZEL) are phase I metabolites of zearalenone, a natural product involved in endocrine disruption and cell proliferation processes. This study aimed to investigate the cytotoxic potential of the hydroethanolic extract of F. chica leaves (HEFc) and determine their protective effects against proliferation induced by α-ZEL and ß-ZEL on human hepatoma HepG2, lung cancer Calu-1, and primary normal human epidermal keratinocytes, neonatal (HEKn). The cytotoxicity of HEFc was measured in a range from 4 to 1000 µg/mL and from 0.4 to 100 µM for both α-ZEL and ß-ZEL. Cell production of intracellular ROS was monitored using the H2-DCFDA probe. The cells exposed to HEFc presented IC50 of 128, 249, and 602 µg/mL for the HepG2, Calu-1, and HEKn cells, respectively. A greater selectivity was seen in HepG2 cells [selectivity index (SI) = 3.5] than in Calu-1 cells (SI = 2.4). Cells treated with mycotoxins remained viable during the first day, and cell proliferation increased at low tested concentrations (0.4-6.3 µM) in all three cell lines. However, after 48 h treatment, cells exposed to 50 and 100 µM of α-ZEL and ß-ZEL displayed decreased viability. HEFc at 16 µg/mL was able to give some protection against cytotoxicity induced by high concentrations of ß-ZEL in HepG2, reducing also cell proliferation elicited at low levels of α-ZEL and ß-ZEL. ROS production was not observed in cells treated with this HEFc concentration; however, it prevented ROS formation induced by treatment with 50 µM α-ZEL or ß-ZEL. In summary, HEFc isolated from plants grown in northern Colombia displayed promising results against cell proliferation and oxidative stress caused by mycotoxins.

Introduction to the Toxins' Special Issue on Evaluation of Cytotoxicity and Cytoprotection Effects of Natural Toxins.

The lifestyle associated with good nutritional quality of food is well known for its widely recognized health benefits, especially when rich in bioactive compounds [...].

Facing Food Risk Perception: Influences of Confinement by SARS-CoV-2 Pandemic in Young Population.

A new food safety level of trust in food risk perception has been noticed, as a consequence of the SARS-CoV-2 pandemic. The pandemic made-up to review nutritional recommendations for the population, mainly for the young population. Here, the results of a designed survey for the young population, from the University of Valencia, Spain, belonging to grades in the health branch of knowledge, and in charge of carrying out the shopping task for their household, are reported. The study reports three different scenarios and years, as defined by the SARS-CoV-2 pandemic: before the pandemic (period January−December 2019), during the pandemic lockdown (period March 2020−August 2020), and after the pandemic lockdown (September 2020−June 2021). The survey was designed with questions, profiling responses using the best−worst elicitation (BWE) format. Results reported that trust and evaluation of information differed in all three scenarios. In the SARS-CoV-2 pandemic, there was (i) a high increase in trust in the information provided inside (by) the shopping place, while there were no changes for the outside (kept in medium score); (ii) trust in cooperative stakeholders went from a medium-low to medium-high score, while, for individual stakeholders, it was maintained as a medium score, and (iii) trust in information on food products was kept in high score. Regarding the evaluation of the information provided by stakeholders, a tendency in medium score was maintained, while that from the channels of distribution went from medium-low to medium-high for buying on-site. A uniform tendency was observed for online/other distribution channels for all three years and descriptors studied: "Internet", "Farmer on-demand", and "Cooperative consumers" (<50%). This research provides findings of implications that contribute to changing the perception of food risk, due to the COVID-19 pandemic, i.e., the adaptation of the young population, trust in safety and quality, and importance of coordination from all communication points to avoid negative or strongest consequences, in case of future lockdowns or health crisis.

Effectiveness of beetroot extract in SH-SY5Y neuronal cell protection against Fumonisin B1, Ochratoxin A and its combination.

Fumonisin B1 (FB1) and ochratoxin A (OTA) are fungal metabolites of worldwide concern because of their effect on human and animal health, as both have been classified by IARC as possible carcinogens (Group 2B). Beetroot is a source of dietary fiber, folic acid, and vitamin C, and some studies have demonstrated their antioxidant activity. Therefore, this work presents the cytoprotective effect of beetroot extract (BRE) on a neuroblastoma cell line (SH-SY5Y cells) exposed to FB1, OTA, and its combination. Cytotoxicity was studied by the MTT ([3-4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay, for 24 h and 48 h. Simultaneous treatment and pre-treatment strategies were tested with 1:512-1:2 and 1:0 dilutions of BRE, with a concentration range from 0.4 to 100 µM of FB1 and from 0.19 to 50 µM of OTA. IC50 values of 5.8 µM and 9.1 µM at 24 h and 48 h, respectively were obtained for OTA while no cytotoxic effect was detected at the concentrations tested for FB1. Cytoprotection with increased viability was obtained when the simultaneous BRE + OTA strategy was performed. Finally, better protection was observed in the pretreatment strategy in which cells were exposed 24 h previously to BRE, compared to that shown in the simultaneous assay.

Effects of Voghiera garlic extracts in neuronal human cell line against zearalenone's derivates and beauvericin.

The Fusarium toxins constitute one of the largest groups of mycotoxins produced by Fusarium species, which are major pathogens of cereal plants. In the present study neuroprotection effect of Allium sativum L garlic extract which is known as Voghiera garlic, from a local garlic ecotype of Ferrara (Italy) was examined on an undifferentiated SH-SY5Y neuronal cells against ZEA's metabolites (α-zearalenol (α-ZEL) and ß-zearalenol (ß-ZEL)) and beauvericin (BEA) mycotoxins which are considered as the most reported Fusarium mycotoxins, via MTT (3-4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay, over 24 h and 48 h through direct treatment, simultaneous treatment and pre-treatment strategies. The results demonstrated remarkable improvement in cells viability in simultaneous and pre-treatment strategy with Voghiera garlic extract (VGE); specifically, for simultaneous treatment of VGE with ß-ZEL which viability increased significantly up to 56%, and subsequently with α-ZEL and BEA by up to 38% and 37% respectively, compared to each mycotoxin tested alone for their highest concentrations assayed, while direct treatments for each mycotoxins individually decreased significantly (for α-ZEL up to 69%, for ß-ZEL 82% and for BEA up to 43%). It is proposed by the present study that VGE extract found to be effective in reducing the cytotoxicity/neurotoxicity of α-ZEL, ß-ZEL and BEA mycotoxins encountered in food and feed commodity.

Application of an In Vitro Digestion Model for Wheat and Red Beetroot Bread to Assess the Bioaccessibility of Aflatoxin B1, Ochratoxin A and Zearalenone and Betalains.

Nowadays, the bakery industry includes different bioactive ingredients to enrich the nutritional properties of its products, such as betalains from red beetroot (Beta vulgaris). However, cereal products are considered a major route of exposure to many mycotoxins, both individually and in combination, due to their daily consumption, if the cereals used contain these toxins. Only the fraction of the contaminant that is released from the food is bioaccessible and bioavailable to produce toxic effects. Foods with bioactive compounds vary widely in chemical structure and function, and some studies have demonstrated their protective effects against toxics. In this study the bioaccessibility and bioavailability of three legislated mycotoxins (AFB1, OTA and ZEN), individual and combined, in two breads, one with wheat flour and the other with wheat flour enriched with 20% Beta vulgaris, were evaluated. Bioaccessibility of these three mycotoxins from wheat bread and red beet bread enriched individually at 100 ng/g was similar between the breads: 16% and 14% for AFB1, 16% and 17% for OTA and 26% and 22% for ZEN, respectively. Whereas, when mycotoxins were co-present these values varied with a decreasing tendency: 9% and 15% for AFB1, 13% and 9% for OTA, 4% and 25% for ZEN in wheat bread and in red beet bread, respectively. These values reveal that the presence of other components and the co-presence of mycotoxins can affect the final bioavailability; however, it is necessary to assess this process with in vivo studies to complete the studies.

Biomarkers of Exposure to Zearalenone in In Vivo and In Vitro Studies.

The measurement of human exposure to mycotoxins is necessary for its association with adverse health effects. This exposure is usually estimated from contamination levels of foodstuffs, which are the primary source of toxin exposure, and data on food consumption patterns. However, variations in contamination level, intestinal absorption, toxin distribution, and excretion lead to individual variations in toxin exposure that can be more readily measured with a biomarker. This review deals with the latest literature information about ZEN biomarkers in humans, animals, and cell line cultures. Their presence in urine, biomarkers that have effects in the kidney, liver, reproductive system and blood and biomarkers of cell response have been reported. It has highlighted the importance of determining α-zearalenol and ß-zearalenol biomarkers to estimate the probable dietary intake (PDI) of a specific population or to characterize the severity of exposure to ZEN in animals or cell lines. α-ZEL and ß-ZEL are cytotoxic by inhibiting cell proliferation, total protein and DNA syntheses, in this sense, an induction of expression proteins Hsp27 and Hsp70 was observed, and an increase in gene expression (TLR4, NF-kBp65, TNF-α, IL-1ß, IL-6, IL-8, MGMT, α-GST, Hsp70, Nrf2, L-Fabp, HO-1, MAPK8), the determination of which indicates an oxidative stress effect. The integrity of the cell or tissue membrane is assessed by lactate dehydrogenase (LDH), which increase at exposure of ZEN (84.2 µM), and the proportions of some fatty acids of the renal tissue membrane were increased at treatments with ZEN. This review allows starting future studies of animal and population exposure in parallel with those of health effects works.

Neurotoxicity of zearalenone's metabolites and beauvericin mycotoxins via apoptosis and cell cycle disruption.

Cell cycle progression and programmed cell death are imposed by pathological stimuli of extrinsic or intrinsic including the exposure to neurotoxins, oxidative stress and DNA damage. All can cause abrupt or delayed cell death, inactivate normal cell survival or cell death networks. Nevertheless, the mechanisms of the neuronal cell death are unresolved. One of the cell deaths triggers which have been wildly studied, correspond to mycotoxins produced by Fusarium species, which have been demonstrated cytotoxicity and neurotoxicity through impairing cell proliferation, gene expression and induction of oxidative stress. The aim of present study was to analyze the cell cycle progression and cell death pathway by flow cytometry in undifferentiated SH-SY5Y neuronal cells exposed to α-zearalenol (α-ZEL), ß-zearalenol (ß-ZEL) and beauvericin (BEA) over 24 h and 48 h individually and combined at the following concentration ranges: from 1.56 to 12.5 µM for α-ZEL and ß-ZEL, from 0.39 to 2.5 µM for BEA, from 1.87 to 25 µM for binary combinations and from 3.43 to 27.5 µM for tertiary combination. Alterations in cell cycle were observed remarkably for ß-ZEL at the highest concentration in all treatments where engaged (ß-ZEL, ß-ZEL + BEA and ß-ZEL + α-ZEL), for both 24 h and 48 h. by activating the cell proliferation in G0/G1 phase (up to 43.6 %) and causing delays or arrests in S and G2/M phases (up to 19.6 %). Tertiary mixtures revealed increases of cell proliferation in subG0 phase by 4-folds versus control. Similarly, for cell death among individual treatments ß-ZEL showed a significant growth in early apoptotic cells population at the highest concentration assayed as well as for all combination treatments where ß-ZEL was involved, in both early apoptotic and apoptotic/necrotic cell death pathways.