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Aflatoxins are fungal metabolites found in feeds and foods. When the ruminants eat feedstuffs containing Aflatoxin B1 (AFB1), this toxin is metabolized and Aflatoxin M1 (AFM1) is excreted in milk. International Agency for Research on Cancer (IARC) classified AFB1 and AFM1 as human carcinogens belonging to Group 1 and Group 2B, respectively, with the formation of DNA adducts. In the last years, some epidemiological studies were conducted on cancer patients aimed to evaluate the effects of AFB1 and AFM1 exposure on cancer cells in order to verify the correlation between toxin exposure and cancer cell proliferation and invasion. In this review, we summarize the activation pathways of AFB1 and AFM1 and the data already reported in literature about their correlation with cancer development and progression. Moreover, considering that few data are still reported about what genes/proteins/miRNAs can be used as damage markers due to AFB1 and AFM1 exposure, we performed a bioinformatic analysis based on interaction network and miRNA predictions to identify a panel of genes/proteins/miRNAs that can be used as targets in further studies for evaluating the effects of the damages induced by AFB1 and AFM1 and their capacity to induce cancer initiation.

In this study, we developed a low-cost, high-sensitivity chemiluminescence competitive aptamer sensor for the detection of aflatoxin B1 (AFB1) in wheat samples. The optical fiber sensor was self-made, and it utilized biotin and streptavidin (SA) link aptamer and horseradish peroxidase (HRP) for the chemiluminescence detection, achieving competitive assay between the AFB1 and AFB1 antigen. We adjusted the experimental conditions of the sensor base on the date of optimization of the experimental conditions and chose coated antigens on the surface of carboxyl magnetic particles. Under conditions optimized by testing key parameters, the assay results showed that the chemiluminescence intensity and AFB1 concentration demonstrated a strong linear relationship (R2 = 0.995), the dynamic range was from 0.1 to 10 ng/mL with a detection limit of 0.09 ng/mL, and the aptamer exhibited good specificity and anti-interference ability. Testing the wheat samples showed that the spiked recovery rate ranged from 79.19% to 113.21%. The sensor possesses characteristics of low detection limits, simple manufacturing methods, and affordability, providing a novel solution for the development of low-cost and high-sensitivity AFB1 detection equipment.

This study examined the effects of fumonisins (FBs) and aflatoxin B1 (AFB1), alone or in combination, on the productivity and health of laying hens, as well as the transfer of aflatoxins (AFs) to chicken food products. The efficacy and safety of mycotoxin detoxifiers (bentonite and fumonisin esterase) to mitigate these effects were also assessed. Laying hens (400) were divided into 20 groups and fed a control, moderate (54.6 µg/kg feed) or high (546 µg/kg feed) AFB1 or FBs (7.9 mg/kg feed) added diets, either alone or in combination, with the mycotoxin detoxifiers added in selected diets. Productivity was evaluated by feed intake, egg weight, egg production, and feed conversion ratio whereas health was assessed by organ weights, blood biochemistry, and mortality. Aflatoxins residues in plasma, liver, muscle, and eggs were determined using UHPLC-MS/MS methods. A diet with AFB1 at a concentration of 546 µg/kg feed decreased egg production and various AFB1-contaminated diets increased serum uric acid levels and weights of liver, spleen, heart, and gizzard. Interactions between AFB1 and FBs significantly impacted spleen, heart, and gizzard weights as well as AFB1 residues in eggs. Maximum AFB1 residues of 0.64 µg/kg and aflatoxin M1 (below limits of quantification) were observed in liver, plasma, and eggs of layers fed diets with AFB1. The mycotoxin detoxifiers reduced effects of AFB1 and FBs on egg production, organ weights, blood biochemistry, and AFB1 residues in tissues. This study highlights the importance of mycotoxin detoxifiers as a mitigation strategy against mycotoxins in poultry production.

A dual-mode immunoassay method was developed for colorimetric and fluorescence detection of aflatoxin B1 (AFB1) based on streptavidin-induced gold nanoparticle aggregation (AuNP@SA). AuNP-modified streptavidin–biotin labeling AFB1 complete antigen aggregations (AuNP@SA@Bio-BSA-AFB1) were synthesized as the competitive binding and dual-mode probe. AuNP@SA@Bio-BSA-AFB1 aggregations possessed high colorimetric and fluorescence quenching intensities. AFB1 antibodies modified immunomagnetic microspheres were used as the capture probe. The competitive binding between AFB1 and AuNP@SA@Bio-BSA-AFB1 leads to changes in color and fluorescence intensity. The detection limit of the colorimetric method is 6.95 ng·mL −1 , while that of the fluorescence method is 0.07 ng·mL −1 . The practicality of the proposed strategy was demonstrated by determining AFB1 in spiked peanut samples. Graphical Abstract

Aflatoxin B1 aldehyde reductase (AFAR) enzyme activity has been associated to a higher resistance to the aflatoxin B1 (AFB1) toxicity in ethoxyquin-fed rats. However, no studies about AFAR activity and its relationship with tolerance to AFB1 have been conducted in poultry. To determine the role of AFAR in poultry tolerance, the hepatic in vitro enzymatic activity of AFAR was investigated in liver cytosol from four commercial poultry species (chicken, quail, turkey and duck). Specifically, the kinetic parameters Vmax, Km and intrinsic clearance (CLint) were determined for AFB1 dialdehyde reductase (AFB1-monoalcohol production) and AFB1 monoalcohol reductase (AFB1-dialcohol production). In all cases, AFB1 monoalcohol reductase activity saturated at the highest aflatoxin B1 dialdehyde concentration tested (66.4 μM), whereas AFB1 dialdehyde reductase did not. Both activities were highly and significantly correlated and therefore are most likely catalyzed by the same AFAR enzyme. However, it appears that production of the AFB1 monoalcohol is favored over the AFB1 dialcohol. The production of alcohols from aflatoxin dialdehyde showed the highest enzymatic efficiency (highest CLint value) in chickens, a species resistant to AFB1; however, it was also high in the turkey, a species with intermediate sensitivity; further, CLint values were lowest in another tolerant species (quail) and in the most sensitive poultry species (the duck). These results suggest that AFAR activity is related to resistance to the acute toxic effects of AFB1 only in chickens and ducks. Genetic selection of ducks for high AFAR activity could be a means to control aflatoxin sensitivity in this poultry species.

Aflatoxin B1 (AFB1) is a mycotoxin widely distributed in a variety of food commodities and exhibits strong toxicity toward multiple tissues and organs. However, little is known about its neurotoxicity and the associated mechanism. In this study, we observed that brain integrity was markedly damaged in mice after intragastric administration of AFB1 (300 μg/kg/day for 30 days). The toxicity of AFB1 on neuronal cells and the underlying mechanisms were then investigated in the neuroblastoma cell line IMR-32. A cell viability assay showed that the IC50 values of AFB1 on IMR-32 cells were 6.18 μg/mL and 5.87 μg/mL after treatment for 24 h and 48 h, respectively. ROS levels in IMR-32 cells increased significantly in a time- and AFB1 concentration-dependent manner, which was associated with the upregulation of NOX2, and downregulation of OXR1, SOD1, and SOD2. Substantial DNA damage associated with the downregulation of PARP1, BRCA2, and RAD51 was also observed. Furthermore, AFB1 significantly induced S-phase arrest, which is associated with the upregulation of CDKN1A, CDKN2C, and CDKN2D. Finally, AFB1 induced apoptosis involving CASP3 and BAX. Taken together, AFB1 manifests a wide range of cytotoxicity on neuronal cells including ROS accumulation, DNA damage, S-phase arrest, and apoptosis—all of which are key factors for understanding the neurotoxicology of AFB1.

Aflatoxins, a group of extremely hazardous compounds because of their genotoxicity and carcinogenicity to human and animals, are commonly found in many tropical and subtropical regions. Ultraviolet (UV) irradiation is proven to be an effective method to reduce or detoxify aflatoxins. However, the degradation products of aflatoxins under UV irradiation and their safety or toxicity have not been clear in practical production such as edible oil industry. In this study, the degradation products of aflatoxin B1 (AFB1) in peanut oil were analyzed by Ultra Performance Liquid Chromatograph-Thermo Quadrupole Exactive Focus mass spectrometry/mass spectrometry (UPLC-TQEF-MS/MS). The high-resolution mass spectra reflected that two main products were formed after the modification of a double bond in the terminal furan ring and the fracture of the lactone ring, while the small molecules especially nitrogen-containing compound may have participated in the photochemical reaction. According to the above results, the possible photodegradation pathway of AFB1 in peanut oil is proposed. Moreover, the human embryo hepatocytes viability assay indicated that the cell toxicity of degradation products after UV irradiation was much lower than that of AFB1, which could be attributed to the breakage of toxicological sites. These findings can provide new information for metabolic pathways and the hazard assessment of AFB1 using UV detoxification.

Our study evaluated aflatoxin B1 (AFB1) levels in packed rice marketed in Lebanon and determined the exposure to this toxin from rice consumption. A total of 105 packed white, parboiled, and brown rice bags were collected. Enzyme-linked immunosorbent assay was used to measure AFB1. A comprehensive food frequency questionnaire was completed by 500 participants to determine patterns of rice consumption and, subsequently, the exposure levels to AFB1 from rice consumption in Lebanon. AFB1 was detected in all rice samples (100%). The average concentration ± standard deviation of AFB1 was 0.5 ± 0.3 μg/kg. Contamination ranged between 0.06 and 2.08 μg/kg. Moisture content in all rice samples was below the recommended percentage (14%). Only 1% of the samples had an AFB1 level above the European Union limit (2 μg/kg). Brown rice had a significantly higher AFB1 level than white and parboiled rice (P = 0.02), while a significant difference was found between both collections for the same brands (P = 0.016). Packing season, packing country, country of origin, presence of a food safety management certification, grain size, and time between packing and purchasing had no significant effect. Exposure to AFB1 from rice consumption in Lebanon was calculated as 0.1 to 2 ng/kg of body weight per day.

Eukaryotes have evolved highly conserved vesicle transport machinery to deliver proteins to the vacuole. In this study we show that the filamentous fungus Aspergillus parasiticus employs this delivery system to perform new cellular functions, the synthesis, compartmentalization, and export of aflatoxin; this secondary metabolite is one of the most potent naturally occurring carcinogens known. Here we show that a highly pure vesicle-vacuole fraction isolated from A. parasiticus under aflatoxin-inducing conditions converts sterigmatocystin, a late intermediate in aflatoxin synthesis, to aflatoxin B₁; these organelles also compartmentalize aflatoxin. The role of vesicles in aflatoxin biosynthesis and export was confirmed by blocking vesicle-vacuole fusion using 2 independent approaches. Disruption of A. parasiticus vb1 (encodes a protein homolog of AvaA, a small GTPase known to regulate vesicle fusion in A. nidulans) or treatment with Sortin3 (blocks Vps16 function, one protein in the class C tethering complex) increased aflatoxin synthesis and export but did not affect aflatoxin gene expression, demonstrating that vesicles and not vacuoles are primarily involved in toxin synthesis and export. We also observed that development of aflatoxigenic vesicles (aflatoxisomes) is strongly enhanced under aflatoxin-inducing growth conditions. Coordination of aflatoxisome development with aflatoxin gene expression is at least in part mediated by Velvet (VeA), a global regulator of Aspergillus secondary metabolism. We propose a unique 2-branch model to illustrate the proposed role for VeA in regulation of aflatoxisome development and aflatoxin gene expression.

It has been known since the early days of the discovery of aflatoxin B1 (AFB1) that there were large species differences in susceptibility to AFB1. It was also evident early on that AFB1 itself was not toxic but required bioactivation to a reactive form. Over the past 60 years there have been thousands of studies to delineate the role of ~10 specific biotransformation pathways of AFB1, both phase I (oxidation, reduction) and phase II (hydrolysis, conjugation, secondary oxidations, and reductions of phase I metabolites). This review provides a historical context and substantive analysis of each of these pathways as contributors to species differences in AFB1 hepatoxicity and carcinogenicity. Since the discovery of AFB1 as the toxic contaminant in groundnut meal that led to Turkey X diseases in 1960, there have been over 15,000 publications related to aflatoxins, of which nearly 8000 have addressed the significance of biotransformation (metabolism, in the older literature) of AFB1. While it is impossible to give justice to all of these studies, this review provides a historical perspective on the major discoveries related to species differences in the biotransformation of AFB1 and sets the stage for discussion of other papers in this Special Issue of the important role that AFB1 metabolites have played as biomarkers of exposure and effect in thousands of human studies on the toxic effects of aflatoxins. Dr. John Groopman has played a leading role in every step of the way—from initial laboratory studies on specific AFB1 metabolites to the application of molecular biomarkers in epidemiological studies associating dietary AFB1 exposure with liver cancer, and the design and conduct of chemoprevention clinical trials to reduce cancer risk from unavoidable aflatoxin exposures by alteration of specific AFB1 biotransformation pathways. This article is written in honor of Dr. Groopman’s many contributions in this area.