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Ji Y, Zhang Y, Si W, Guo J, Liu G, Wang C, Khan MZ, Zhao X, Liu W. Aflatoxin B1-Induced Apoptosis in Donkey Kidney via EndoG-Mediated Endoplasmic Reticulum Stress. Vet Sci 2025; 12:130. [PMID: 40005890 PMCID: PMC11860441 DOI: 10.3390/vetsci12020130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 01/16/2025] [Accepted: 01/21/2025] [Indexed: 02/27/2025] Open
Abstract
Aflatoxin B1 (AFB1) is a prevalent environmental and forage contaminant that poses significant health risks to both humans and livestock due to its toxic effects on various organs and systems. Among its toxicological effects, nephrotoxicity is a hallmark of AFB1 exposure. However, the precise mechanisms underlying AFB1-induced kidney damage in donkeys remain poorly understood. To investigate this, we established a donkey model exposed to AFB1 by administering a diet supplemented with 1 mg AFB1/kg for 30 days. Kidney apoptosis was assessed using TUNEL staining, while gene expression and protein levels of Endonuclease G (EndoG), as well as genes related to endoplasmic reticulum (ER) stress and apoptosis, were quantified by RT-qPCR and Western blotting. Our findings indicate that AFB1 exposure resulted in significant kidney injury, apoptosis, and oxidative stress. Notably, AFB1 exposure upregulated the expression of EndoG and promoted its translocation to the ER, which subsequently induced ER stress and activated the mitochondrial apoptotic pathway. These results suggest that AFB1-induced kidney damage in donkeys is mediated through the oxidative stress and mitochondrial apoptosis pathways, primarily involving the EndoG-IRE1/ATF6-CHOP signaling axis.
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Affiliation(s)
| | | | | | | | | | | | | | - Xia Zhao
- College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China
| | - Wenqiang Liu
- College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China
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Eaton DL, Williams DE, Coulombe RA. Species Differences in the Biotransformation of Aflatoxin B1: Primary Determinants of Relative Carcinogenic Potency in Different Animal Species. Toxins (Basel) 2025; 17:30. [PMID: 39852983 PMCID: PMC11768628 DOI: 10.3390/toxins17010030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 12/30/2024] [Accepted: 01/05/2025] [Indexed: 01/26/2025] Open
Abstract
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.
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Affiliation(s)
- David L. Eaton
- Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA 98195, USA
| | - David E. Williams
- Environmental and Molecular Toxicology, College of Agricultural Sciences, Oregon State University, Corvalis, OR 97331, USA;
| | - Roger A. Coulombe
- Graduate Toxicology Program, Department of Veterinary Sciences, Utah State University, Logan, UT 84322, USA;
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Kibugu J, Munga L, Mburu D, Maloba F, Auma JE, Grace D, Lindahl JF. Dietary Mycotoxins: An Overview on Toxicokinetics, Toxicodynamics, Toxicity, Epidemiology, Detection, and Their Mitigation with Special Emphasis on Aflatoxicosis in Humans and Animals. Toxins (Basel) 2024; 16:483. [PMID: 39591238 PMCID: PMC11598113 DOI: 10.3390/toxins16110483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 10/04/2024] [Accepted: 10/10/2024] [Indexed: 11/28/2024] Open
Abstract
Mycotoxins are secondary metabolites of filamentous fungi and ubiquitous dietary contaminants. Aflatoxins, a group of mycotoxins with high prevalence and toxicity, have raised a high level of public health concern, the most prevalent and toxic being aflatoxin B1 (AFB1). Many aspects appertaining to AFB1 poisoning are not well understood. Yet this information is necessary to devise appropriate surveillance and mitigation strategies against human and animal aflatoxicosis. This review provides an in-depth update of work carried out on mycotoxin poisoning, particularly aflatoxicosis in humans and animals, to identify gaps in knowledge. Hypotheses explaining the functional significance of mycotoxins in fungal biology and their dietary epidemiological data are presented and briefly discussed. The toxicology of aflatoxins and the challenges of their mitigation are discussed in depth. It was concluded that the identification of potential mycotoxin-hazard-prone food items and quantification of the associated risk of cancer ailments in humans is a prime priority. There is a dearth of reliable sampling methodologies for estimating AFB1 in animal feed. Data update on AFB1 in animal feed and its implication in animal production, mitigation strategies, and elucidation of risk factors to this hazard is required. To reduce the burden of aflatoxins, surveillance employing predictive technology, and biocontrol strategies seem promising approaches.
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Affiliation(s)
- James Kibugu
- Biotechnology Research Institute, Kenya Agricultural and Livestock Research Organization, P.O. Box 362, Kikuyu 00902, Kenya;
- Department of Biochemistry, Microbiology and Biotechnology, School of Pure and Applied Sciences, Kenyatta University, P.O. Box 43844, Nairobi 00100, Kenya;
| | - Leonard Munga
- Department of Animal Science, School of Agriculture and Environmental Sciences, Kenyatta University, P.O. Box 43844, Nairobi 00100, Kenya;
| | - David Mburu
- Department of Biochemistry, Microbiology and Biotechnology, School of Pure and Applied Sciences, Kenyatta University, P.O. Box 43844, Nairobi 00100, Kenya;
| | - Fredrick Maloba
- Department of Zoological Sciences, School of Pure and Applied Sciences, Kenyatta University, P.O. Box 43844, Nairobi 00100, Kenya;
| | - Joanna E. Auma
- Biotechnology Research Institute, Kenya Agricultural and Livestock Research Organization, P.O. Box 362, Kikuyu 00902, Kenya;
| | - Delia Grace
- Department of Biosciences, International Livestock Research Institute, P.O. Box 30709, Nairobi 00100, Kenya;
- Natural Resources Institute, University of Greenwich, UK, Central Avenue, Chatham ME4 4TB, UK
| | - Johanna F. Lindahl
- Department of Animal Health and Antibiotic Strategies, Swedish Veterinary Agency, 75189 Uppsala, Sweden;
- Department of Medical Biochemistry and Microbiology, Uppsala University, 75123 Uppsala, Sweden
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Gerdemann A, Cramer B, Degen GH, Veerkamp J, Günther G, Albrecht W, Behrens M, Esselen M, Ghallab A, Hengstler JG, Humpf HU. Comparative metabolism of aflatoxin B 1 in mouse, rat and human primary hepatocytes using HPLC-MS/MS. Arch Toxicol 2023; 97:3179-3196. [PMID: 37794256 PMCID: PMC10567917 DOI: 10.1007/s00204-023-03607-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Accepted: 09/14/2023] [Indexed: 10/06/2023]
Abstract
Aflatoxin B1 (AFB1) is a highly hepatotoxic and carcinogenic mycotoxin produced by Aspergillus species. The compound is mainly metabolized in the liver and its metabolism varies between species. The present study quantified relevant AFB1- metabolites formed by mouse, rat, and human primary hepatocytes after treatment with 1 µM and 10 µM AFB1. The use of liquid chromatographic separation coupled with tandem mass spectrometric detection enabled the selective and sensitive determination of phase I and phase II metabolites of AFB1 over incubation times of up to 24 h. The binding of AFB1 to macromolecules was also considered. The fastest metabolism of AFB1 was observed in mouse hepatocytes which formed aflatoxin P1 as a major metabolite and also its glucuronidated form, while AFP1 occurred only in traces in the other species. Aflatoxin M1 was formed in all species and was, together with aflatoxin Q1 and aflatoxicol, the main metabolite in human cells. Effective epoxidation led to high amounts of DNA adducts already 30 min post-treatment, especially in rat hepatocytes. Lower levels of DNA adducts and fast DNA repair were found in mouse hepatocytes. Also, protein adducts arising from reactive intermediates were formed rapidly in all three species. Detoxification via glutathione conjugation and subsequent formation of the N-acetylcysteine derivative appeared to be similar in mice and in rats and strongly differed from human hepatocytes which did not form these metabolites at all. The use of qualitative reference material of a multitude of metabolites and the comparison of hepatocyte metabolism in three species using advanced methods enabled considerations on toxification and detoxification mechanisms of AFB1. In addition to glutathione conjugation, phase I metabolism is strongly involved in the detoxification of AFB1.
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Affiliation(s)
- Andrea Gerdemann
- Institute of Food Chemistry, University of Münster, Corrensstraße 45, 48149 Münster, Germany
| | - Benedikt Cramer
- Institute of Food Chemistry, University of Münster, Corrensstraße 45, 48149 Münster, Germany
| | - Gisela H. Degen
- Leibniz Research Centre for Working Environment and Human Factors (IfADo), Ardeystraße 67, 44139 Dortmund, Germany
| | - Jannik Veerkamp
- Institute of Food Chemistry, University of Münster, Corrensstraße 45, 48149 Münster, Germany
| | - Georgia Günther
- Leibniz Research Centre for Working Environment and Human Factors (IfADo), Ardeystraße 67, 44139 Dortmund, Germany
| | - Wiebke Albrecht
- Leibniz Research Centre for Working Environment and Human Factors (IfADo), Ardeystraße 67, 44139 Dortmund, Germany
| | - Matthias Behrens
- Institute of Food Chemistry, University of Münster, Corrensstraße 45, 48149 Münster, Germany
| | - Melanie Esselen
- Institute of Food Chemistry, University of Münster, Corrensstraße 45, 48149 Münster, Germany
| | - Ahmed Ghallab
- Leibniz Research Centre for Working Environment and Human Factors (IfADo), Ardeystraße 67, 44139 Dortmund, Germany
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, South Valley University, Qena, 83523 Egypt
| | - Jan G. Hengstler
- Leibniz Research Centre for Working Environment and Human Factors (IfADo), Ardeystraße 67, 44139 Dortmund, Germany
| | - Hans-Ulrich Humpf
- Institute of Food Chemistry, University of Münster, Corrensstraße 45, 48149 Münster, Germany
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Cox A, Bomstein Z, Jayaraman A, Allred C. The intestinal microbiota as mediators between dietary contaminants and host health. Exp Biol Med (Maywood) 2023; 248:2131-2150. [PMID: 37997859 PMCID: PMC10800128 DOI: 10.1177/15353702231208486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2023] Open
Abstract
The gut microbiota sit at an important interface between the host and the environment, and are exposed to a multitude of nutritive and non-nutritive substances. These microbiota are critical to maintaining host health, but their supportive roles may be compromised in response to endogenous compounds. Numerous non-nutritive substances are introduced through contaminated foods, with three common groups of contaminants being bisphenols, phthalates, and mycotoxins. The former contaminants are commonly introduced through food and/or beverages packaged in plastic, while mycotoxins contaminate various crops used to feed livestock and humans alike. Each group of contaminants have been shown to shift microbial communities following exposure; however, specific patterns in microbial responses have yet to be identified, and little is known about the capacity of the microbiota to metabolize these contaminants. This review characterizes the state of existing research related to gut microbial responses to and biotransformation of bisphenols, phthalates, and mycotoxins. Collectively, we highlight the need to identify consistent, contaminant-specific responses in microbial shifts, whether these community alterations are a result of contaminant effects on the host or microbiota directly, and to identify the extent of contaminant biotransformation by microbiota, including if these transformations occur in physiologically relevant contexts.
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Affiliation(s)
- Amon Cox
- Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843, USA
| | - Zach Bomstein
- Department of Nutrition, University of North Carolina Greensboro, Greensboro, NC 27412, USA
| | - Arul Jayaraman
- Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843, USA
| | - Clinton Allred
- Department of Nutrition, University of North Carolina Greensboro, Greensboro, NC 27412, USA
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Jaćević V, Dumanović J, Alomar SY, Resanović R, Milovanović Z, Nepovimova E, Wu Q, Franca TCC, Wu W, Kuča K. Research update on aflatoxins toxicity, metabolism, distribution, and detection: A concise overview. Toxicology 2023; 492:153549. [PMID: 37209941 DOI: 10.1016/j.tox.2023.153549] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 05/07/2023] [Accepted: 05/17/2023] [Indexed: 05/22/2023]
Abstract
Serious health risks associated with the consumption of food products contaminated with aflatoxins (AFs) are worldwide recognized and depend predominantly on consumed AF concentration by diet. A low concentration of aflatoxins in cereals and related food commodities is unavoidable, especially in subtropic and tropic regions. Accordingly, risk assessment guidelines established by regulatory bodies in different countries help in the prevention of aflatoxin intoxication and the protection of public health. By assessing the maximal levels of aflatoxins in food products which are a potential risk to human health, it's possible to establish appropriate risk management strategies. Regarding, a few factors are crucial for making a rational risk management decision, such as toxicological profile, adequate information concerning the exposure duration, availability of routine and some novel analytical techniques, socioeconomic factors, food intake patterns, and maximal allowed levels of each aflatoxin in different food products which may be varied between countries.
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Affiliation(s)
- Vesna Jaćević
- Department for Experimental Pharmacology and Toxicology, National Poison Control Centre, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia; Medical Faculty of the Military Medical Academy, University of Defence, Crnotravska 17, 11000 Belgrade, Serbia; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanského 62, 500 03 Hradec Králové, Czech Republic.
| | - Jelena Dumanović
- Medical Faculty of the Military Medical Academy, University of Defence, Crnotravska 17, 11000 Belgrade, Serbia; Department of Analytical Chemistry, Faculty of Chemistry, University of Belgrade, 11158 Belgrade, Serbia
| | - Suliman Y Alomar
- King Saud University, College of Science, Zoology Department, Riyadh, 11451, Saudi Arabia
| | - Radmila Resanović
- Faculty of Veterinary Medicine, University of Belgrade, Bulevar Oslobođenja 18, 11000 Belgrade, Serbia
| | - Zoran Milovanović
- Special Police Unit, Ministry of Interior, Trebevićka 12/A, 11 030 Belgrade, Serbia
| | - Eugenie Nepovimova
- Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanského 62, 500 03 Hradec Králové, Czech Republic
| | - Qinghua Wu
- College of Life Science, Yangtze University, 1 Nanhuan Road, 434023 Jingzhou, Hubei, China; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanského 62, 500 03 Hradec Králové, Czech Republic
| | - Tanos Celmar Costa Franca
- Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense, Military Institute of Engineering, Praça General Tibúrcio 80, Rio de Janeiro, RJ 22290-270, Brazil; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanského 62, 500 03 Hradec Králové, Czech Republic
| | - Wenda Wu
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanského 62, 500 03 Hradec Králové, Czech Republic
| | - Kamil Kuča
- Biomedical Research Center, University Hospital Hradec Kralove, 50005, Hradec Kralove, Czech Republic; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanského 62, 500 03 Hradec Králové, Czech Republic
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7
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Du X, Schrunk DE, Imerman PM, Tahara J, Tkachenko A, Guag J, Reimschuessel R, Rumbeiha WK. Extensive Evaluation of a Method for Quantitative Measurement of Aflatoxins B1 and M1 in Animal Urine Using High-Performance Liquid Chromatography with Fluorescence Detection. J AOAC Int 2023; 106:645-651. [PMID: 36912688 PMCID: PMC10156413 DOI: 10.1093/jaoacint/qsad034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 01/17/2023] [Accepted: 01/31/2023] [Indexed: 03/14/2023]
Abstract
BACKGROUND Aflatoxins (AFs) are common feed contaminants and are one of the common causes of toxin-related pet food poisoning and recalls. OBJECTIVE Currently, there are no validated methods for the detection and quantitation of AFs in biological matrices to diagnose AF exposure in live animals. Following a successful intra-laboratory method development to quantify AFB1 and AFM1 in animal urine by HPLC with fluorescence detection (HPLC-FLD), the present study was conducted to extensively evaluate the method performance in an unbiased manner using blinded samples. METHODS The evaluation included two stages. First, the performance was verified in the method-originating laboratory in a single-laboratory blinded method test (BMT-S) trial followed by a multi-laboratory blinded method test (BMT-M) trial. RESULTS In both trials, accuracy, repeatability, and reproducibility were satisfactory confirming the relatively good ruggedness and robustness of the method and ensuring that it will perform as expected if used by other laboratories in the future. CONCLUSIONS We extensively evaluated the performance of a quantitative method to detect AFB1 and AFM1 in animal urine by HPLC-FLD by two different laboratories in two separate BMT-S and BMT-M trials. Both BMT results demonstrated the satisfactory accuracy and precision of the method. It is now available to be adopted by other diagnostic laboratories for purposes of diagnosing AF intoxication in animals. HIGHLIGHTS A simple urine-based diagnostic test method using HPLC-FLD that originated in a single laboratory now has passed a multi-laboratory evaluation and is now available to be shared with other diagnostic laboratories for purposes of diagnosing AF intoxication in animals so better treatment can be rendered.
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Affiliation(s)
- Xiangwei Du
- Veterinary Medical Diagnostic Laboratory, Department of Biomedical Sciences, University of Missouri, 901 East Campus Loop, Columbia, MO 65211, USA
| | - Dwayne E Schrunk
- Veterinary Diagnostic Laboratory, Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, 1850 Christensen Dr, Ames, IA 50011, USA
| | - Paula M Imerman
- Veterinary Diagnostic Laboratory, Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, 1850 Christensen Dr, Ames, IA 50011, USA
| | - John Tahara
- California Animal Health and Food Safety Laboratory System, Toxicology Laboratory, University of California, Davis, CA 95616, USA
| | - Andriy Tkachenko
- United States Food and Drug Administration, Center for Veterinary Medicine, 8401 Muirkirk Rd, Laurel, MD 20708, USA
| | - Jake Guag
- United States Food and Drug Administration, Center for Veterinary Medicine, 8401 Muirkirk Rd, Laurel, MD 20708, USA
| | - Renate Reimschuessel
- United States Food and Drug Administration, Center for Veterinary Medicine, 8401 Muirkirk Rd, Laurel, MD 20708, USA
| | - Wilson K Rumbeiha
- Department of Molecular Biosciences, University of California, Davis, CA 95616, USA
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Loi M, De Leonardis S, Ciasca B, Paciolla C, Mulè G, Haidukowski M. Aflatoxin B 1 Degradation by Ery4 Laccase: From In Vitro to Contaminated Corn. Toxins (Basel) 2023; 15:toxins15050310. [PMID: 37235345 DOI: 10.3390/toxins15050310] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 04/17/2023] [Accepted: 04/24/2023] [Indexed: 05/28/2023] Open
Abstract
Aflatoxins (AFs) are toxic secondary metabolites produced by Aspergillus spp. and are found in food and feed as contaminants worldwide. Due to climate change, AFs occurrence is expected to increase also in western Europe. Therefore, to ensure food and feed safety, it is mandatory to develop green technologies for AFs reduction in contaminated matrices. With this regard, enzymatic degradation is an effective and environmentally friendly approach under mild operational conditions and with minor impact on the food and feed matrix. In this work, Ery4 laccase, acetosyringone, ascorbic acid, and dehydroascorbic acid were investigated in vitro, then applied in artificially contaminated corn for AFB1 reduction. AFB1 (0.1 µg/mL) was completely removed in vitro and reduced by 26% in corn. Several degradation products were detected in vitro by UHPLC-HRMS and likely corresponded to AFQ1, epi-AFQ1, AFB1-diol, or AFB1dialehyde, AFB2a, and AFM1. Protein content was not altered by the enzymatic treatment, while slightly higher levels of lipid peroxidation and H2O2 were detected. Although further studies are needed to improve AFB1 reduction and reduce the impact of this treatment in corn, the results of this study are promising and suggest that Ery4 laccase can be effectively applied for the reduction in AFB1 in corn.
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Affiliation(s)
- Martina Loi
- Institute of Sciences of Food Production, National Research Council of Italy (CNR), Via Amendola 122/O, 70126 Bari, Italy
| | - Silvana De Leonardis
- Department of Biosciences, Biotechnology and Environment, Università degli Studi di Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy
| | - Biancamaria Ciasca
- Institute of Sciences of Food Production, National Research Council of Italy (CNR), Via Amendola 122/O, 70126 Bari, Italy
| | - Costantino Paciolla
- Department of Biosciences, Biotechnology and Environment, Università degli Studi di Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy
| | - Giuseppina Mulè
- Institute of Sciences of Food Production, National Research Council of Italy (CNR), Via Amendola 122/O, 70126 Bari, Italy
| | - Miriam Haidukowski
- Institute of Sciences of Food Production, National Research Council of Italy (CNR), Via Amendola 122/O, 70126 Bari, Italy
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9
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Qureshi MA, Amir M, Khan RH, Musarrat J, Javed S. Glycation reduces the binding dynamics of aflatoxin B 1 to human serum albumin: a comprehensive spectroscopic and computational investigation. J Biomol Struct Dyn 2023; 41:14797-14811. [PMID: 37021366 DOI: 10.1080/07391102.2023.2194000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 02/25/2023] [Indexed: 04/07/2023]
Abstract
Aflatoxin B1 (AFB1), a potent mutagen, is synthesized by Aspergillus parasiticus and Aspergillus flavus. Human serum albumin (HSA) is a globular protein with diverse roles. As AFB1 is ingested with food and is transported in the body via blood, it becomes pertinent to comprehend the effect of the binding of this toxin on the structure and conformation of HSA, which may help to get insight into the toxic effect of the exposure of the mycotoxin. In this study, multi-spectroscopic approaches have been used to evaluate the binding efficiency of AFB1 with both the native HSA (nHSA) and the glycated HSA (gHSA). Steady-state fluorescence spectroscopy reveals the static type of fluorescence quenching in the fluorescence emission spectra of nHSA and gHSA in the presence of AFB1. The binding constant (Kb) is calculated to be 6.88 × 104 M-1 for nHSA, while a reduced Kb value of 2.95 × 104 M-1 has been obtained for gHSA. The circular dichroism study confirms the change in the secondary structure of nHSA and gHSA in the presence of AFB1, followed by alterations in the melting temperature (Tm) of nHSA and gHSA. In silico computational findings envisaged the amino acid residues and bonds involved in the binding of nHSA and gHSA with AFB1. The comprehensive study analyzes the binding effectiveness of AFB1 with nHSA and gHSA and shows reduced binding of AFB1 to gHSA.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Mohd Aamir Qureshi
- Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, India
| | - Mohd Amir
- Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, India
| | - Rizwan Hasan Khan
- Interdisciplinary Biotechnology Unit, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, India
| | - Javed Musarrat
- Department of Agricultural Microbiology, Faculty of Agricultural Sciences, Aligarh Muslim University, Aligarh, India
| | - Saleem Javed
- Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, India
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10
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Tebbi CK. Mycoviruses in Fungi: Carcinogenesis of Fungal Agents May Not Always Be Mycotoxin Related. J Fungi (Basel) 2023; 9:jof9030368. [PMID: 36983536 PMCID: PMC10052198 DOI: 10.3390/jof9030368] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 03/02/2023] [Accepted: 03/09/2023] [Indexed: 03/30/2023] Open
Abstract
Certain viruses have been found to induce diverse biological pathways to carcinogenesis, evidenced by the presence of viral gene products in some tumors. Despite the fact that many fungal agents contain mycoviruses, until recently, their possible direct effects on human health, including carcinogenesis and leukemogenesis, had not been explored. In this regard, most studies of fungal agents have rightly concentrated on their mycotoxin formation and effects. Recently, the direct role of yeasts and fungi in the etiology of cancers, including leukemia, have been investigated. While greater attention has been placed on the carcinogenic effects of Candida, the role of filamentous fungi in carcinogenesis has also been explored. Recent findings from studies using the enzyme-linked immunosorbent assay (ELISA) technique indicate that the plasma of patients with acute lymphoblastic leukemia (ALL) uniformly contains antibodies for a certain mycovirus-containing Aspergillus flavus, while controls are negative. The exposure of mononuclear leukocytes from patients with ALL in full remission, and long-term survivors, to the product of this organism was reported to result in the re-development of typical genetics and cell surface phenotypes characteristic of active ALL. Mycoviruses are known to be able to significantly alter the biological characteristics and functions of their host. The possible carcinogenic and leukemogenic role of mycoviruses, with and without their host, needs to be further investigated.
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Affiliation(s)
- Cameron K Tebbi
- Children's Cancer Research Group Laboratory, 13719 North Nebraska Avenue, Suite #108, Tampa, FL 33613-3305, USA
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Benkerroum N, Ismail A. Human Breast Milk Contamination with Aflatoxins, Impact on Children's Health, and Possible Control Means: A Review. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:16792. [PMID: 36554670 PMCID: PMC9779431 DOI: 10.3390/ijerph192416792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 12/08/2022] [Accepted: 12/12/2022] [Indexed: 06/17/2023]
Abstract
Aflatoxins are natural toxicants produced mainly by species of the Aspergillus genus, which contaminate virtually all feeds and foods. Apart from their deleterious health effects on humans and animals, they can be secreted unmodified or carried over into the milk of lactating females, thereby posing health risks to suckling babies. Aflatoxin M1 (AFM1) is the major and most toxic aflatoxin type after aflatoxin B1 (AFB1). It contaminates human breast milk upon direct ingestion from dairy products or by carry-over from the parent molecule (AFB1), which is hydroxylated in the liver and possibly in the mammary glands by cytochrome oxidase enzymes and then excreted into breast milk as AFM1 during lactation via the mammary alveolar epithelial cells. This puts suckling infants and children fed on this milk at a high risk, especially that their detoxifying activities are still weak at this age essentially due to immature liver as the main organ responsible for the detoxification of xenobiotics. The occurrence of AFM1 at toxic levels in human breast milk and associated health conditions in nursing children is well documented, with developing countries being the most affected. Different studies have demonstrated that contamination of human breast milk with AFM1 represents a real public health issue, which should be promptly and properly addressed to reduce its incidence. To this end, different actions have been suggested, including a wider and proper implementation of regulatory measures, not only for breast milk but also for foods and feeds as the upstream sources for breast milk contamination with AFM1. The promotion of awareness of lactating mothers through the organization of training sessions and mass media disclosures before and after parturition is of a paramount importance for the success of any action. This is especially relevant that there are no possible control measures to ensure compliance of lactating mothers to specific regulatory measures, which can yet be appropriate for the expansion of breast milk banks in industrialized countries and emergence of breast milk sellers. This review attempted to revisit the public health issues raised by mother milk contamination with AFM1, which remains undermined despite the numerous relevant publications highlighting the needs to tackle its incidence as a protective measure for the children physical and mental health.
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Affiliation(s)
- Noreddine Benkerroum
- Expertise Aliments Santé, Food Health Consultancy, 7450 Dollier Str., Montréal, QC H1S 2J6, Canada
| | - Amir Ismail
- Institute of Food Science and Nutrition, Bahauddin Zakariya University, Multan 60000, Pakistan
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12
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Tian M, Zhang G, Ding S, Jiang Y, Jiang B, Ren D, Chen P. Lactobacillus plantarum T3 as an adsorbent of aflatoxin B1 effectively mitigates the toxic effects on mice. FOOD BIOSCI 2022. [DOI: 10.1016/j.fbio.2022.101984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
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13
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Krausová M, Ayeni KI, Wisgrill L, Ezekiel CN, Braun D, Warth B. Trace analysis of emerging and regulated mycotoxins in infant stool by LC-MS/MS. Anal Bioanal Chem 2022; 414:7503-7516. [PMID: 34932144 PMCID: PMC9482899 DOI: 10.1007/s00216-021-03803-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 11/12/2021] [Accepted: 11/23/2021] [Indexed: 11/30/2022]
Abstract
Infants are sensitive to negative effects caused by food contaminants such as mycotoxins. To date, analytical methods assessing mycotoxin mixture exposure in infant stool are absent. Herein, we present a novel multi-mycotoxin LC-MS/MS assay capable of detecting 30+ analytes including the regulated mycotoxin classes (aflatoxins, trichothecenes, ochratoxins, zearalenone, citrinin), emerging Alternaria and Fusarium toxins, and several key metabolites. Sample preparation consisted of a 'dilute, filter, and shoot' approach. The method was in-house validated and demonstrated that 25 analytes fulfilled all required criteria despite the high diversity of chemical structures included. Extraction recoveries for most of the analytes were in the range of 65-114% with standard deviations below 30% and limits of detection between 0.03 and 11.3 ng/g dry weight. To prove the methods' applicability, 22 human stool samples from premature Austrian infants (n = 12) and 12-month-old Nigerian infants (n = 10) were analyzed. The majority of the Nigerian samples were contaminated with alternariol monomethyl ether (8/10) and fumonisin B1 (8/10), while fumonisin B2 and citrinin were quantified in some samples. No mycotoxins were detected in any of the Austrian samples. The method can be used for sensitive human biomonitoring (HBM) purposes and to support exposure and, potentially, risk assessment of mycotoxins. Moreover, it allows for investigating potential associations between toxicant exposure and the infants' developing gut microbiome.
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Affiliation(s)
- Magdaléna Krausová
- Faculty of Chemistry, Department of Food Chemistry and Toxicology, University of Vienna, Währinger Straße 38, 1090, Vienna, Austria
| | - Kolawole I Ayeni
- Faculty of Chemistry, Department of Food Chemistry and Toxicology, University of Vienna, Währinger Straße 38, 1090, Vienna, Austria
- Department of Microbiology, Babcock University, Ilishan Remo, Ogun State, Nigeria
| | - Lukas Wisgrill
- Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Comprehensive Center for Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 1090, Vienna, Austria
| | - Chibundu N Ezekiel
- Department of Microbiology, Babcock University, Ilishan Remo, Ogun State, Nigeria
| | - Dominik Braun
- Faculty of Chemistry, Department of Food Chemistry and Toxicology, University of Vienna, Währinger Straße 38, 1090, Vienna, Austria
| | - Benedikt Warth
- Faculty of Chemistry, Department of Food Chemistry and Toxicology, University of Vienna, Währinger Straße 38, 1090, Vienna, Austria.
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14
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Li C, Liu X, Wu J, Ji X, Xu Q. Research progress in toxicological effects and mechanism of aflatoxin B 1 toxin. PeerJ 2022; 10:e13850. [PMID: 35945939 PMCID: PMC9357370 DOI: 10.7717/peerj.13850] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 07/16/2022] [Indexed: 01/18/2023] Open
Abstract
Fungal contamination of animal feed can severely affect the health of farm animals, and result in considerable economic losses. Certain filamentous fungi or molds produce toxic secondary metabolites known as mycotoxins, of which aflatoxins (AFTs) are considered the most critical dietary risk factor for both humans and animals. AFTs are ubiquitous in the environment, soil, and food crops, and aflatoxin B1(AFB1) has been identified by the World Health Organization (WHO) as one of the most potent natural group 1A carcinogen. We reviewed the literature on the toxic effects of AFB1 in humans and animals along with its toxicokinetic properties. The damage induced by AFB1 in cells and tissues is mainly achieved through cell cycle arrest and inhibition of cell proliferation, and the induction of apoptosis, oxidative stress, endoplasmic reticulum (ER) stress and autophagy. In addition, numerous coding genes and non-coding RNAs have been identified that regulate AFB1 toxicity. This review is a summary of the current research on the complexity of AFB1 toxicity, and provides insights into the molecular mechanisms as well as the phenotypic characteristics.
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Affiliation(s)
- Congcong Li
- College of Animal Science and Technology, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan, China
| | - Xiangdong Liu
- Huazhong Agricultural University, Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Lab of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Wuhan, Hubei, China
| | - Jiao Wu
- College of Animal Science and Technology, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan, China
| | - Xiangbo Ji
- Henan University of Animal Husbandry and Economy, Henan Key Laboratory of Unconventional Feed Resources Innovative Utilization, Zhengzhou, Henan, China
| | - Qiuliang Xu
- College of Animal Science and Technology, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan, China
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15
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The effect of curcumin on some cytokines, antioxidants and liver function tests in rats induced by Aflatoxin B1. Heliyon 2022; 8:e09890. [PMID: 35874069 PMCID: PMC9304732 DOI: 10.1016/j.heliyon.2022.e09890] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Revised: 04/09/2022] [Accepted: 07/01/2022] [Indexed: 11/23/2022] Open
Abstract
Aflatoxins are common food contaminants threating human and animal health. Aflatoxin B1 (AFB1) toxication can lead to important health issues. Recent studies have revealed the therapeutic effect of curcumin (Cur) and have drawn attention in the pharmaceutical industry. The therapeutic efficacy of Cur on AFB1-induced oxidative stress, pro-inflammatory response, and hepatorenal damage has not been adequately studied. This study was conducted to evaluate the protective efficacy of Cur on several lipid peroxidation and antioxidant defense system enzymes, some pro-inflammatory cytokines, and liver function tests in rats suffering from chronic aflatoxicosis induced by AFB1 administered for sixty days. Rats were divided into five groups; Control (K), Dimethyl sulfoxide (D), Curcumin (Cur; 300 mg/kg/day, orally), AFB1 (AF; 250 μg/kg/day, oral) and AFB1+ Curcumin (AF + Cur). Oxidative stress caused by AFB1 caused an increase in Malondialdehyde (MDA), a lipid peroxidation product, and a decrease in glutathione (GSH) and superoxide dismutase (SOD) activities. In addition, AFB1 led to increased levels of pro-inflammatory cytokines such as tumor necrosis factor-a (TNF-a), interleukin-1b (IL-1b), and interleukin-6 (IL-6). Liver function tests after chronic exposure to AFB1 showed that this toxic substance causes liver damage. Concomitant Cur administration normalized AFB1-induced oxidative damage, inflammatory response, and liver functions. This therapeutic effect of Cur on AFB1 was thought to be related to its antioxidant and anti-inflammatory activities. Our results suggest that CUR supplementation in food as it shows beneficial effects particularly on liver impairment exerted by AFB1.
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16
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SILVA JVBD, OLIVEIRA CAFD, RAMALHO LNZ. An overview of mycotoxins, their pathogenic effects, foods where they are found and their diagnostic biomarkers. FOOD SCIENCE AND TECHNOLOGY 2022. [DOI: 10.1590/fst.48520] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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17
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Ezekiel CN, Abia WA, Braun D, Šarkanj B, Ayeni KI, Oyedele OA, Michael-Chikezie EC, Ezekiel VC, Mark BN, Ahuchaogu CP, Krska R, Sulyok M, Turner PC, Warth B. Mycotoxin exposure biomonitoring in breastfed and non-exclusively breastfed Nigerian children. ENVIRONMENT INTERNATIONAL 2022; 158:106996. [PMID: 34991256 DOI: 10.1016/j.envint.2021.106996] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 11/19/2021] [Accepted: 11/20/2021] [Indexed: 06/14/2023]
Abstract
A multi-specimen, multi-mycotoxin approach involving ultra-sensitive LC-MS/MS analysis of breast milk, complementary food and urine was applied to examine mycotoxin co-exposure in 65 infants, aged 1-18 months, in Ogun state, Nigeria. Aflatoxin M1 was detected in breast milk (4/22 (18%)), while six other classes of mycotoxins were quantified; including dihydrocitrinone (6/22 (27%); range: 14.0-59.7 ng/L) and sterigmatocystin (1/22 (5%); 1.2 ng/L) detected for the first time. Seven distinct classes of mycotoxins including aflatoxins (9/42 (21%); range: 1.0-16.2 µg/kg) and fumonisins (12/42 (29%); range: 7.9-194 µg/kg) contaminated complementary food. Mycotoxins covering seven distinct classes with diverse structures and modes of action were detected in 64/65 (99%) of the urine samples, demonstrating ubiquitous exposure. Two aflatoxin metabolites (AFM1 and AFQ1) and FB1 were detected in 6/65 (9%), 44/65 (68%) and 17/65 (26%) of urine samples, respectively. Mixtures of mycotoxin classes were common, including 22/22 (100%), 14/42 (33%) and 56/65 (86%) samples having 2-6, 2-4, or 2-6 mycotoxins present, for breast milk, complementary food and urine, respectively. Aflatoxin and/or fumonisin was detected in 4/22 (18%), 12/42 (29%) and 46/65 (71%) for breast milk, complimentary foods and urine, respectively. Furthermore, the detection frequency, median concentrations and occurrence of mixtures were typically greater in urine of non-exclusively breastfed compared to exclusively breastfed infants. The study provides novel insights into mycotoxin co-exposures in early-life. Albeit a small sample set, it highlights transition to higher levels of infant mycotoxin exposure as complementary foods are introduced, providing impetus to mitigate during this critical early-life period and encourage breastfeeding.
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Affiliation(s)
- Chibundu N Ezekiel
- Department of Microbiology, Babcock University, Ilishan Remo, Ogun State, Nigeria; University of Natural Resources and Life Sciences, Vienna, Department of Agrobiotechnology, IFA-Tulln, Institute of Bioanalytics and Agro-Metabolomics, Konrad-Lorenz-Strasse 20, 3430 Tulln an der Donau, Austria.
| | - Wilfred A Abia
- University of Natural Resources and Life Sciences, Vienna, Department of Agrobiotechnology, IFA-Tulln, Institute of Bioanalytics and Agro-Metabolomics, Konrad-Lorenz-Strasse 20, 3430 Tulln an der Donau, Austria; Queen's University Belfast, School of Biological Sciences, Institute for Global Food Security, University Road, Belfast BT7 1NN, Northern Ireland, UK; Laboratory of Pharmacology and Toxicology, Department of Biochemistry, Faculty of Science, University of Yaounde I, P.O. Box 812, Yaounde, Cameroon
| | - Dominik Braun
- University of Vienna, Faculty of Chemistry, Department of Food Chemistry and Toxicology, Währinger Str. 38, A-1090 Vienna, Austria
| | - Bojan Šarkanj
- University of Natural Resources and Life Sciences, Vienna, Department of Agrobiotechnology, IFA-Tulln, Institute of Bioanalytics and Agro-Metabolomics, Konrad-Lorenz-Strasse 20, 3430 Tulln an der Donau, Austria; Department of Food Technology, University North, Center Koprivnica, Trg dr. Zarka Dolinara 1, HR, 48000 Koprivnica, Croatia
| | - Kolawole I Ayeni
- Department of Microbiology, Babcock University, Ilishan Remo, Ogun State, Nigeria
| | | | - Emmanuel C Michael-Chikezie
- Clifford University, Owerrinta (Ihie Campus), Abia State, Nigeria; Benjamin Carson (Snr.) School of Medicine, Babcock University, Ilishan Remo, Ogun State, Nigeria
| | | | - Beatrice N Mark
- Department of Community Health, Babcock University Teaching Hospital, Ilishan Remo, Ogun State, Nigeria
| | - Chinonso P Ahuchaogu
- Department of Clinical Sciences, Babcock University Teaching Hospital, Ilishan Remo, Ogun State, Nigeria
| | - Rudolf Krska
- University of Natural Resources and Life Sciences, Vienna, Department of Agrobiotechnology, IFA-Tulln, Institute of Bioanalytics and Agro-Metabolomics, Konrad-Lorenz-Strasse 20, 3430 Tulln an der Donau, Austria; Queen's University Belfast, School of Biological Sciences, Institute for Global Food Security, University Road, Belfast BT7 1NN, Northern Ireland, UK
| | - Michael Sulyok
- University of Natural Resources and Life Sciences, Vienna, Department of Agrobiotechnology, IFA-Tulln, Institute of Bioanalytics and Agro-Metabolomics, Konrad-Lorenz-Strasse 20, 3430 Tulln an der Donau, Austria
| | - Paul C Turner
- MIAEH, School of Public Health, University of Maryland, College Park, MD 20742, USA
| | - Benedikt Warth
- University of Vienna, Faculty of Chemistry, Department of Food Chemistry and Toxicology, Währinger Str. 38, A-1090 Vienna, Austria.
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18
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Braun D, Abia WA, Šarkanj B, Sulyok M, Waldhoer T, Erber AC, Krska R, Turner PC, Marko D, Ezekiel CN, Warth B. Mycotoxin-mixture assessment in mother-infant pairs in Nigeria: From mothers' meal to infants' urine. CHEMOSPHERE 2022; 287:132226. [PMID: 34826919 DOI: 10.1016/j.chemosphere.2021.132226] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 08/27/2021] [Accepted: 09/07/2021] [Indexed: 06/13/2023]
Abstract
Exposure to food and environmental contaminants is a global environmental health issue. In this study, innovative LC-MS/MS approaches were applied to investigate mycotoxin co-exposure in mother-infant pairs (n = 23) by analyzing matched plate-ready food, breast milk and urine samples of mothers and their exclusively breastfed infants. The study revealed frequent co-occurrence of two to five mycotoxins. Regulated (e.g. aflatoxins, deoxynivalenol and ochratoxin A) and emerging mycotoxins (e.g. alternariol monomethyl ether and beauvericin) were frequently detected (3 %-89 % and 45 %-100 %), in at least one specimen. In addition, a moderate association of ochratoxin A in milk to urine of mothers (r = 0.47; p = 0.003) and infants (r = 0.52; p = 0.019) but no other significant correlations were found. Average concentration levels in food mostly did not exceed European maximum residue limits, and intake estimates demonstrated exposure below tolerable daily intake values. Infants were exposed to significantly lower toxin levels compared to their mothers, indicating the protective effect of breastfeeding. However, the transfer into milk and urine and the resulting chronic low-dose exposure warrant further monitoring. In the future, occurrence of mycotoxin-mixtures, and their combined toxicological effects need to be comprehensively considered and implemented in risk management strategies. These should aim to minimize early-life exposure in critical developmental stages.
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Affiliation(s)
- Dominik Braun
- University of Vienna, Faculty of Chemistry, Department of Food Chemistry and Toxicology, Währinger Straße 38, 1090, Vienna, Austria
| | - Wilfred A Abia
- Institute of Bioanalytics and Agro-Metabolomics, Department of Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences Vienna (BOKU), Konrad Lorenzstr. 20, A-3430, Tulln, Austria; Laboratory of Pharmacology and Toxicology, Department of Biochemistry, Faculty of Science, University of Yaounde I, P.O. Box 812, Yaounde, Cameroon; Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, University Road, Belfast, BT7 1NN, Northern Ireland, United Kingdom
| | - Bojan Šarkanj
- Institute of Bioanalytics and Agro-Metabolomics, Department of Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences Vienna (BOKU), Konrad Lorenzstr. 20, A-3430, Tulln, Austria; Department of Food Technology, University Centre Koprivnica, University North, Trg dr. Žarka Dolinara 1, HR-48000, Koprivnica, Croatia
| | - Michael Sulyok
- Institute of Bioanalytics and Agro-Metabolomics, Department of Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences Vienna (BOKU), Konrad Lorenzstr. 20, A-3430, Tulln, Austria
| | - Thomas Waldhoer
- Department of Epidemiology, Center for Public Health, Medical University of Vienna, Austria
| | - Astrid C Erber
- Department of Epidemiology, Center for Public Health, Medical University of Vienna, Austria; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, New Richards Building, Old Road Campus, Roosevelt Drive, Oxford, OX3 7LG, UK
| | - Rudolf Krska
- Institute of Bioanalytics and Agro-Metabolomics, Department of Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences Vienna (BOKU), Konrad Lorenzstr. 20, A-3430, Tulln, Austria; Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, University Road, Belfast, BT7 1NN, Northern Ireland, United Kingdom
| | - Paul C Turner
- MIAEH, School of Public Health, University of Maryland, College Park, MD, 20742, USA
| | - Doris Marko
- University of Vienna, Faculty of Chemistry, Department of Food Chemistry and Toxicology, Währinger Straße 38, 1090, Vienna, Austria
| | - Chibundu N Ezekiel
- Institute of Bioanalytics and Agro-Metabolomics, Department of Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences Vienna (BOKU), Konrad Lorenzstr. 20, A-3430, Tulln, Austria; Department of Microbiology, Babcock University, Ilishan Remo, Ogun State, Nigeria.
| | - Benedikt Warth
- University of Vienna, Faculty of Chemistry, Department of Food Chemistry and Toxicology, Währinger Straße 38, 1090, Vienna, Austria.
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19
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Cao W, Yu P, Yang K, Cao D. Aflatoxin B1: metabolism, toxicology, and its involvement in oxidative stress and cancer development. Toxicol Mech Methods 2021; 32:395-419. [PMID: 34930097 DOI: 10.1080/15376516.2021.2021339] [Citation(s) in RCA: 102] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Aflatoxins are a class of carcinogenic mycotoxins produced by Aspergillus fungi, which are widely distributed in nature. Aflatoxin B1 (AFB1) is the most toxic of these compounds and its metabolites have a variety of biological activities, including acute toxicity, teratogenicity, mutagenicity and carcinogenicity, which has been well-characterized to lead to the development of hepatocellular carcinoma (HCC) in humans and animals. This review focuses on the metabolism of AFB1, including epoxidation and DNA adduction, as it concerns the initiation of cancer and the underlying mechanisms. In addition to DNA adduction, inflammation and oxidative stress caused by AFB1 can also participate in the occurrence of cancer. Therefore, the main carcinogenic mechanism of AFB1 related ROS is summarized. This review also describes recent reports of AFB1 exposures in occupational settings. It is hoped that people will pay more attention to occupational health, in order to reduce the incidence of cancer caused by occupational exposure.
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Affiliation(s)
- Weiya Cao
- Medical school, Anhui University of Science & Technology, Huainan 232001, China
| | - Pan Yu
- Medical school, Anhui University of Science & Technology, Huainan 232001, China
| | - KePeng Yang
- Medical school, Anhui University of Science & Technology, Huainan 232001, China
| | - Dongli Cao
- Medical school, Anhui University of Science & Technology, Huainan 232001, China
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20
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Urinary Biomarkers of Mycotoxin Induced Nephrotoxicity-Current Status and Expected Future Trends. Toxins (Basel) 2021; 13:toxins13120848. [PMID: 34941686 PMCID: PMC8708607 DOI: 10.3390/toxins13120848] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 11/19/2021] [Accepted: 11/24/2021] [Indexed: 12/18/2022] Open
Abstract
The intensifying world-wide spread of mycotoxigenic fungal species has increased the possibility of mycotoxin contamination in animal feed and the human food chain. Growing evidence shows the deleterious toxicological effects of mycotoxins from infants to adults, while large population-based screening programs are often missing to identify affected individuals. The kidney functions as the major excretory system, which makes it particularly vulnerable to nephrotoxic injury. However, few studies have attempted to screen for kidney injury biomarkers in large, mycotoxin-exposed populations. As a result, there is an urgent need to screen them with sensitive biomarkers for potential nephrotoxicity. Although a plethora of biomarkers have been tested to estimate the harmful effects of a wide spectrum of toxicants, β2-microglobulin (β2-MG) and N-acetyl-β-D-glucosaminidase (NAG) are currently the dominant biomarkers employed routinely in environmental toxicology research. Nevertheless, kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are also emerging as useful and informative markers to reveal mycotoxin induced nephrotoxicity. In this opinion article we consider the nephrotoxic effects of mycotoxins, the biomarkers available to detect and quantify the kidney injuries caused by them, and to recommend biomarkers to screen mycotoxin-exposed populations for renal damage.
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21
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Analysis of Aflatoxin Biomarkers in the Hair of Experimental Animals. Toxins (Basel) 2021; 13:toxins13080570. [PMID: 34437441 PMCID: PMC8402374 DOI: 10.3390/toxins13080570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 07/17/2021] [Accepted: 07/20/2021] [Indexed: 11/20/2022] Open
Abstract
Analysis of body fluids and tissues of aflatoxin exposed individuals for the presence of aflatoxins and aflatoxin metabolites has emerged as a reliable indicator of exposure and metabolism of aflatoxins. However, current aflatoxin biomarkers are not appropriate for investigating the long-term effects of aflatoxin exposure. In this explorative study, we investigated the analysis of hair as a complementary or alternative matrix for the assessment of biomarkers of long-term aflatoxin exposure. Three groups of guinea pigs were orally dosed with 5 ugkg−1bw−1, 50 ugkg−1bw−1, and 100 ugkg−1bw−1 of AFB1. Urine and hair samples were collected on days 0, 1, 2, 3, 7, 30, 60, and 90 and analysed for AFB1 and AFM1 using UHPLC-MS/MS. AFB1 and AFM1 were detected in 75% and 13.6%, respectively, of the day 1 to day 7 urine samples. AFB1 was detected in hair samples collected from day 3 up to day 60. This is the first report to confirm the deposition of AFB1 in the hair of experimental animals. These findings indicate that hair analysis has the potential to provide an accurate long-term historical record of aflatoxin exposure with potentially important implications for the field of aflatoxin biomarkers.
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Screening of the aflatoxin M 1 metabolite in urine samples of residents in Terengganu, Malaysia. Toxicon 2020; 186:120-125. [PMID: 32771393 DOI: 10.1016/j.toxicon.2020.07.022] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 07/02/2020] [Accepted: 07/22/2020] [Indexed: 11/21/2022]
Abstract
A study was conducted to screen the occurrence and level of aflatoxin M1 (AFM1) in urine samples of 206 urban and rural residents in Terengganu, Malaysia. The level of AFM1 was quantified by competitive enzyme-linked immune-absorbent assay (ELISA). Of the 206 samples, 84 were positive for AFM1 (40.8%) in a range of 0.07-5.53 ng/ml (mean = 0.589 ng/ml). Residents of Terengganu are moderately exposed to AFM1. Age, ethnicity, marital status and employment status were associated with urinary level of AFM1. Subjects aged 30 years and above, non-Malays, married, and those unemployed had significantly higher levels of urinary AFM1 (p < 0.05). Since aflatoxin is recognised as a potent-carcinogen for liver cancer and a continuous exposure to this toxin can be fatal, the present findings could provide a baseline for future studies where larger samples and more advanced techniques might be used to find the possible effects of the exposure of this toxin on the community's health.
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Gilbert‐Sandoval I, Wesseling S, Rietjens IMCM. Predicting the Acute Liver Toxicity of Aflatoxin B1 in Rats and Humans by an In Vitro-In Silico Testing Strategy. Mol Nutr Food Res 2020; 64:e2000063. [PMID: 32421213 PMCID: PMC7379280 DOI: 10.1002/mnfr.202000063] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Revised: 05/01/2020] [Indexed: 11/14/2022]
Abstract
SCOPE High-level exposure to aflatoxin B1 (AFB1) is known to cause acute liver damage and fatality in animals and humans. The intakes actually causing this acute toxicity have so far been estimated based on AFB1 levels in contaminated foods or biomarkers in serum. The aim of the present study is to predict the doses causing acute liver toxicity of AFB1 in rats and humans by an in vitro-in silico testing strategy. METHODS AND RESULTS Physiologically based kinetic (PBK) models for AFB1 in rats and humans are developed. The models are used to translate in vitro concentration-response curves for cytotoxicity in primary rat and human hepatocytes to in vivo dose-response curves using reverse dosimetry. From these data, the dose levels at which toxicity would be expected are obtained and compared to toxic dose levels from available rat and human case studies on AFB1 toxicity. The results show that the in vitro-in silico testing strategy can predict dose levels causing acute toxicity of AFB1 in rats and human. CONCLUSIONS Quantitative in vitro in vivo extrapolation (QIVIVE) using PBK modeling-based reverse dosimetry can predict AFB1 doses that cause acute liver toxicity in rats and human.
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Affiliation(s)
- Ixchel Gilbert‐Sandoval
- Division of ToxicologyWageningen University and ResearchStippeneng 4Wageningen6708 WEThe Netherlands
| | - Sebastiaan Wesseling
- Division of ToxicologyWageningen University and ResearchStippeneng 4Wageningen6708 WEThe Netherlands
| | - Ivonne M. C. M. Rietjens
- Division of ToxicologyWageningen University and ResearchStippeneng 4Wageningen6708 WEThe Netherlands
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Karayağiz Muslu G, Özdemir M. Occurrence of and Factors Associated With the Presence of Aflatoxin M 1 in Breast Milk of Mothers in Fethiye, Turkey. Biol Res Nurs 2020; 22:362-368. [PMID: 32314592 DOI: 10.1177/1099800420919900] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Aflatoxins comprise a group of mycotoxins that are found in the environment. Exposure to aflatoxins has been reported to cause serious health problems in humans. Since aflatoxin M1 (AFM1) is secreted in breast milk, the exposure of infants to this toxin is an important concern. The aim of this study was to determine the prevalence, levels of, and factors associated with the presence of AFM1 in breast milk of mothers in Fethiye, Turkey. Breast milk samples were taken from 100 mothers who had given birth over the period of October-November 2017. The AFM1 content of the samples was determined via enzyme-linked immunosorbent assay. The lowest limit for milk samples in the Ridascreen® AFM1 commercial test kit is 5 ng/L. Because of this, AFM1 levels below 5 ng/L in the breast milk samples were assessed as negative. Of the breast milk samples tested, 53 were positive. The average AFM1 amount in the positive samples was 6.36 ng/L (ppt; range 5.10-8.31 ng/L). Mothers who were housewives, lived in damp, humid houses, or ate spices or dried fruits and vegetables had significantly greater prevalence of AFM1 in their breast milk than those who were employed, did not report dampness or mold in the home, or did not eat spices or dried fruits and vegetables. AFM1 in breast milk could be an important risk factor for infant health. Informing the public about food safety could reduce the amount of AFM1 being transferred into breast milk via food channels.
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Affiliation(s)
- Gonca Karayağiz Muslu
- Department of Nursing, Fethiye Faculty of Health Sciences, Muğla Sıtkı Koçman University, Turkey
| | - Mehmet Özdemir
- Department of Medical Pharmacology, Faculty of Medicine, Karabük University, Turkey
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Ferri F, Brera C, De Santis B, Collini G, Crespi E, Debegnach F, Gargano A, Gattei D, Magnani I, Mancuso P, Mozzanica S, Teodori E, Djuric O, Giorgi Rossi P. Association between Urinary Levels of Aflatoxin and Consumption of Food Linked to Maize or Cow Milk or Dairy Products. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17072510. [PMID: 32268619 PMCID: PMC7177871 DOI: 10.3390/ijerph17072510] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 03/28/2020] [Accepted: 03/30/2020] [Indexed: 11/16/2022]
Abstract
The aim of this analysis was to assess the association between consumption of maize and dairy products and urine and serum levels of aflatoxin FM1 (AFM1) in a sample of 59 males occupationally exposed (29) and non-exposed (30) to aflatoxins. Two urine samples were collected for each person; each sample was accompanied by a questionnaire on food consumption in the preceding 96 h. Given the similar levels of contamination found in exposed and non-exposed workers, the association between food consumption and AFM1 levels was analyzed by pooling samples from exposed and non-exposed workers. No serum sample was found to be positive for AFM1, whereas 74% of the urine samples were positive; the average concentration of positive samples was 0.042 ng/mL (range < limit of detection (LoD) (0.002)-0.399 ng/mL). Of the 21 samples from maize consumers, 13 were positive for AFM1 (62%), with a mean concentration of 0.026 ng/mL (range 0.006-0.088 ng/mL), while 76% (74/94) of the samples from maize non-consumers were positive (mean 0.045, range < LoD (0.002)-0.399 ng/mL). No association was found with milk or dairy products. The high urine level of aflatoxins found in both exposed and non-exposed workers was not associated with the consumption of maize or cow milk products.
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Affiliation(s)
- Fulvio Ferri
- Servizio Prevenzione Sicurezza Ambienti di Lavoro (SPSAL), Azienda Unità Sanitaria Locale—Reggio Emilia—IRCCS, Via Amendola 2, 42122 Reggio Emilia, Italy (E.C.); (A.G.); (D.G.); (I.M.); (S.M.)
| | - Carlo Brera
- Laboratorio Nazionale di Riferimento (LNR) per le Micotossine—Istituto Superiore di Sanità, Roma, Viale Regina Elena 299, 00161 Rome, Italy; (C.B.); (B.D.S.); (F.D.)
| | - Barbara De Santis
- Laboratorio Nazionale di Riferimento (LNR) per le Micotossine—Istituto Superiore di Sanità, Roma, Viale Regina Elena 299, 00161 Rome, Italy; (C.B.); (B.D.S.); (F.D.)
| | - Giorgia Collini
- Servizio di Epidemiologia, Azienda Unità Sanitaria Locale—IRCCS di Reggio Emilia, Via Amendola 2, 42122 Reggio Emilia, Italy; (P.M.); (O.D.); (P.G.R.)
- Correspondence:
| | - Enrica Crespi
- Servizio Prevenzione Sicurezza Ambienti di Lavoro (SPSAL), Azienda Unità Sanitaria Locale—Reggio Emilia—IRCCS, Via Amendola 2, 42122 Reggio Emilia, Italy (E.C.); (A.G.); (D.G.); (I.M.); (S.M.)
| | - Francesca Debegnach
- Laboratorio Nazionale di Riferimento (LNR) per le Micotossine—Istituto Superiore di Sanità, Roma, Viale Regina Elena 299, 00161 Rome, Italy; (C.B.); (B.D.S.); (F.D.)
| | - Angelo Gargano
- Servizio Prevenzione Sicurezza Ambienti di Lavoro (SPSAL), Azienda Unità Sanitaria Locale—Reggio Emilia—IRCCS, Via Amendola 2, 42122 Reggio Emilia, Italy (E.C.); (A.G.); (D.G.); (I.M.); (S.M.)
| | - Daniela Gattei
- Servizio Prevenzione Sicurezza Ambienti di Lavoro (SPSAL), Azienda Unità Sanitaria Locale—Reggio Emilia—IRCCS, Via Amendola 2, 42122 Reggio Emilia, Italy (E.C.); (A.G.); (D.G.); (I.M.); (S.M.)
| | - Ines Magnani
- Servizio Prevenzione Sicurezza Ambienti di Lavoro (SPSAL), Azienda Unità Sanitaria Locale—Reggio Emilia—IRCCS, Via Amendola 2, 42122 Reggio Emilia, Italy (E.C.); (A.G.); (D.G.); (I.M.); (S.M.)
| | - Pamela Mancuso
- Servizio di Epidemiologia, Azienda Unità Sanitaria Locale—IRCCS di Reggio Emilia, Via Amendola 2, 42122 Reggio Emilia, Italy; (P.M.); (O.D.); (P.G.R.)
| | - Stefania Mozzanica
- Servizio Prevenzione Sicurezza Ambienti di Lavoro (SPSAL), Azienda Unità Sanitaria Locale—Reggio Emilia—IRCCS, Via Amendola 2, 42122 Reggio Emilia, Italy (E.C.); (A.G.); (D.G.); (I.M.); (S.M.)
| | - Elvira Teodori
- Laboratorio Analisi, Azienda Unità Sanitaria Locale—IRCCS di Reggio Emilia, Via Amendola 2, 42122 Reggio Emilia, Italy;
| | - Olivera Djuric
- Servizio di Epidemiologia, Azienda Unità Sanitaria Locale—IRCCS di Reggio Emilia, Via Amendola 2, 42122 Reggio Emilia, Italy; (P.M.); (O.D.); (P.G.R.)
- Center for Environmental, Nutritional and Genetic Epidemiology (CREAGEN), Section of Public Health, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Università 4, 41121 Modena, Italy
| | - Paolo Giorgi Rossi
- Servizio di Epidemiologia, Azienda Unità Sanitaria Locale—IRCCS di Reggio Emilia, Via Amendola 2, 42122 Reggio Emilia, Italy; (P.M.); (O.D.); (P.G.R.)
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EFSA Panel on Contaminants in the Food Chain (CONTAM), Schrenk D, Bignami M, Bodin L, Chipman JK, del Mazo J, Grasl‐Kraupp B, Hogstrand C, Hoogenboom L(R, Leblanc J, Nebbia CS, Nielsen E, Ntzani E, Petersen A, Sand S, Schwerdtle T, Vleminckx C, Marko D, Oswald IP, Piersma A, Routledge M, Schlatter J, Baert K, Gergelova P, Wallace H. Risk assessment of aflatoxins in food. EFSA J 2020; 18:e06040. [PMID: 32874256 PMCID: PMC7447885 DOI: 10.2903/j.efsa.2020.6040] [Citation(s) in RCA: 140] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
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.
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27
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Jurišić N, Schwartz-Zimmermann HE, Kunz-Vekiru E, Moll WD, Schweiger W, Fowler J, Berthiller F. Determination of aflatoxin biomarkers in excreta and ileal content of chickens. Poult Sci 2020; 98:5551-5561. [PMID: 31198963 DOI: 10.3382/ps/pez308] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 05/29/2019] [Indexed: 01/16/2023] Open
Abstract
Aflatoxins are carcinogenic secondary metabolites frequently detected in food and feed stuff based on maize and other crops susceptible to infection with the fungal pathogen Aspergillus flavus. We investigated the metabolization of aflatoxins in chickens by analyzing excreta and ileal content and developed and validated a biomarker method for detection of aflatoxins and their metabolites in these matrices. Analysis of ileal content served to distinguish between urinary and fecal excretion combined in the excreta samples. During a 3-wk animal trial, one hundred sixty-eight 1-day-old chicks were randomly allocated to 24 pens with 7 chicks per pen and subjected to different feed regimens with: A) toxin-free feed, B) feed supplemented with 18 ng of total aflatoxins/g, and C) feed supplemented with 515 ng of total aflatoxins/g. Chicken excreta and ileal content were sampled after 7, 14, and 21 D. An analytical method based on liquid chromatography coupled to tandem mass spectrometry was validated for the determination of aflatoxin B1, B2, G1, G2, M1, P1, Q1, and aflatoxin B1-N7-guanine (AFB1-N7-Gua) in chicken's samples. Comparing chicken excreta, which contain urine and feces, to ileal content, which contains no urine, we explored the secretion pathway of aflatoxin metabolites. The AFB1-N7-Gua was only detected in excreta, whereas aflatoxin M1 (AFM1) was detected both in ileal content and excreta. Aflatoxin M1 was detected in excreta in concentrations 5 times higher than in ileal content, suggesting primary excretion via urine. Although chickens are relatively resistant to aflatoxins, contamination of feed can lead to adverse effects and thus economic losses in farming. Therefore, a biomarker method to estimate the exposure of chickens to aflatoxins can play an important role to monitor the animals' health.
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Affiliation(s)
- N Jurišić
- Christian Doppler Laboratory for Mycotoxin Metabolism, Center for Analytical Chemistry, Department of Agrobiotechnology (IFA-Tulln), University of Natural Sciences and Life Sciences, Vienna (BOKU), 3430 Tulln, Austria
| | - H E Schwartz-Zimmermann
- Christian Doppler Laboratory for Mycotoxin Metabolism, Center for Analytical Chemistry, Department of Agrobiotechnology (IFA-Tulln), University of Natural Sciences and Life Sciences, Vienna (BOKU), 3430 Tulln, Austria
| | - E Kunz-Vekiru
- Christian Doppler Laboratory for Mycotoxin Metabolism, Center for Analytical Chemistry, Department of Agrobiotechnology (IFA-Tulln), University of Natural Sciences and Life Sciences, Vienna (BOKU), 3430 Tulln, Austria
| | - W D Moll
- BIOMIN Holding GmbH, BIOMIN Research Center, 3430 Tulln, Austria
| | - W Schweiger
- BIOMIN Holding GmbH, BIOMIN Research Center, 3430 Tulln, Austria
| | - J Fowler
- Department of Poultry Science, University of Georgia, 30602 Athens, GA, USA
| | - F Berthiller
- Christian Doppler Laboratory for Mycotoxin Metabolism, Center for Analytical Chemistry, Department of Agrobiotechnology (IFA-Tulln), University of Natural Sciences and Life Sciences, Vienna (BOKU), 3430 Tulln, Austria
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28
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Benkerroum N. Retrospective and Prospective Look at Aflatoxin Research and Development from a Practical Standpoint. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:E3633. [PMID: 31569703 PMCID: PMC6801849 DOI: 10.3390/ijerph16193633] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Revised: 09/24/2019] [Accepted: 09/26/2019] [Indexed: 12/19/2022]
Abstract
Among the array of structurally and toxicologically diverse mycotoxins, aflatoxins have attracted the most interest of scientific research due to their high toxicity and incidence in foods and feeds. Despite the undeniable progress made in various aspects related to aflatoxins, the ultimate goal consisting of reducing the associated public health risks worldwide is far from being reached due to multiplicity of social, political, economic, geographic, climatic, and development factors. However, a reasonable degree of health protection is attained in industrialized countries owing to their scientific, administrative, and financial capacities allowing them to use high-tech agricultural management systems. Less fortunate situations exist in equatorial and sub-equatorial developing countries mainly practicing traditional agriculture managed by smallholders for subsistence, and where the climate is suitable for mould growth and aflatoxin production. This situation worsens due to climatic change producing conditions increasingly suitable for aflatoxigenic mould growth and toxin production. Accordingly, it is difficult to harmonize the regulatory standards of aflatoxins worldwide, which prevents agri-foods of developing countries from accessing the markets of industrialized countries. To tackle the multi-faceted aflatoxin problem, actions should be taken collectively by the international community involving scientific research, technological and social development, environment protection, awareness promotion, etc. International cooperation should foster technology transfer and exchange of pertinent technical information. This review presents the main historical discoveries leading to our present knowledge on aflatoxins and the challenges that should be addressed presently and in the future at various levels to ensure higher health protection for everybody. In short, it aims to elucidate where we come from and where we should go in terms of aflatoxin research/development.
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Affiliation(s)
- Noreddine Benkerroum
- Department of Food Science and Agricultural Chemistry, Macdonald-Stewart Building, McGill University, Macdonald Campus, 21,111 Lakeshore Road, Sainte-Anne-de-Bellevue, QC H9X 3V9, Canada.
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29
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Li S, Muhammad I, Yu H, Sun X, Zhang X. Detection of Aflatoxin adducts as potential markers and the role of curcumin in alleviating AFB1-induced liver damage in chickens. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2019; 176:137-145. [PMID: 30925330 DOI: 10.1016/j.ecoenv.2019.03.089] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 02/23/2019] [Accepted: 03/20/2019] [Indexed: 06/09/2023]
Abstract
In this study, we identified AFB1 adducts as potential markers and investigated the role of curcumin in alleviating AFB1-induced liver damage by suppressing the production of AFB1 adducts and oxidative stress in AA broilers liver. A total of 64 one-day-old Arbor Acres (AA) broilers were randomly divided into four groups, including control group, AFB1 group (5 mg/kg AFB1), cur + AFB1 group (300 mg/kg curcumin+5 mg/kg AFB1) and curcumin group (300 mg/kg). Serum biochemical parameters, liver antioxidant abilities, AFB1 adducts and oxidative stress mechanism were studied in broilers. AFB1 administration accompany with signs of liver injury, including hepatic histological lesions, increased serum enzymes activities, decreased liver antioxidant enzymes activities and the suppression of ROS and 8-OHdG. Meanwhile, Nrf2/HO-1 pathway was depressed by AFB1 treatment. Immunohistochemistry and ELISA showed that AFB1 significantly increased AFB1-DNA adduct in liver (p < 0.05) and AFB1-lysine adduct in serum (p < 0.05). Importantly, supplementation of curcumin can ameliorate these alterations. Intriguingly, curcumin alleviated AFB1-induced toxicity and oxidative stress by inhibiting the generation of ROS, 8-OHdG and AFB1 adducts, and activated Nrf2 signaling pathway in broilers. Conclusively, our experiments suggest that curcumin could be considered as a potential agent for prevention of AFB1-induced toxicity and oxidative stress, and AFB1 adducts could be suitable therapeutic targets.
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Affiliation(s)
- Sihong Li
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development. Faculty of Basic Veterinary Science, College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Xiangfang District, Harbin, PR China
| | - Ishfaq Muhammad
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development. Faculty of Basic Veterinary Science, College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Xiangfang District, Harbin, PR China
| | - Hongxiao Yu
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development. Faculty of Basic Veterinary Science, College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Xiangfang District, Harbin, PR China
| | - Xiaoqi Sun
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development. Faculty of Basic Veterinary Science, College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Xiangfang District, Harbin, PR China
| | - Xiuying Zhang
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development. Faculty of Basic Veterinary Science, College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Xiangfang District, Harbin, PR China.
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30
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Slobodchikova I, Sivakumar R, Rahman MS, Vuckovic D. Characterization of Phase I and Glucuronide Phase II Metabolites of 17 Mycotoxins Using Liquid Chromatography-High-Resolution Mass Spectrometry. Toxins (Basel) 2019; 11:E433. [PMID: 31344861 PMCID: PMC6723440 DOI: 10.3390/toxins11080433] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Revised: 07/18/2019] [Accepted: 07/19/2019] [Indexed: 12/12/2022] Open
Abstract
Routine mycotoxin biomonitoring methods do not include many mycotoxin phase I and phase II metabolites, which may significantly underestimate mycotoxin exposure especially for heavily metabolized mycotoxins. Additional research efforts are also needed to measure metabolites in vivo after exposure and to establish which mycotoxin metabolites should be prioritized for the inclusion during large-scale biomonitoring efforts. The objective of this study was to perform human in vitro microsomal incubations of 17 mycotoxins and systematically characterize all resulting metabolites using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). The results obtained were then used to build a comprehensive LC-MS library and expand a validated 17-mycotoxin method for exposure monitoring to screening of additional 188 metabolites, including 100 metabolites reported for the first time. The final method represents one of the most comprehensive LC-HRMS methods for mycotoxin biomonitoring or metabolism/fate studies.
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Affiliation(s)
- Irina Slobodchikova
- Department of Chemistry and Biochemistry, Concordia University, 7141 Sherbrooke Street West, Montreal, QC H4B 1R6, Canada
- Centre for Biological Applications of Mass Spectrometry, Concordia University, 7141 Sherbrooke Street West, Montreal, QC H4B 1R6, Canada
| | - Reajean Sivakumar
- Department of Chemistry and Biochemistry, Concordia University, 7141 Sherbrooke Street West, Montreal, QC H4B 1R6, Canada
| | - Md Samiur Rahman
- Department of Chemistry and Biochemistry, Concordia University, 7141 Sherbrooke Street West, Montreal, QC H4B 1R6, Canada
| | - Dajana Vuckovic
- Department of Chemistry and Biochemistry, Concordia University, 7141 Sherbrooke Street West, Montreal, QC H4B 1R6, Canada.
- Centre for Biological Applications of Mass Spectrometry, Concordia University, 7141 Sherbrooke Street West, Montreal, QC H4B 1R6, Canada.
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31
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Nikbakht E, Jamaluddin R, Redzwan SM, Khalesi S. Oral administration of Lactobacillus casei Shirota can ameliorate the adverse effect of an acute aflatoxin exposure in Sprague Dawley rats. INT J VITAM NUTR RES 2019; 88:199-208. [PMID: 31056010 DOI: 10.1024/0300-9831/a000513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Aflatoxin B1(AFB1) is a toxic compound commonly found in some crops with an adverse health effect on human and animals. Some beneficial microorganisms (or probiotics) such as lactic acid bacteria have shown the ability to reduce the bioavailability of aflatoxins and its intestinal absorption. However, the dose and duration of aflatoxins exposure and probiotic treatment can influence the ability of probiotics to remove aflatoxins. Therefore, this research aimed to investigate the efficacy of oral probiotic Lactobacillus casei Shirota strain (LcS) induction in an acute exposure to AFB1 in rats. Experimentally, Sprague Dawley rats were divided into three groups: AFB1 only (n = 9); AFB1 treated with LcS (n = 9); and control (no AFB1 exposure) (n = 6) groups. The blood AFB1 level of rats treated with LcS was slightly lower than the untreated AFB1 induced rats (11.12 ± 0.71 vs 10.93 ± 0.69 ng g-1). Also, LcS treatment slightly moderated the liver and kidney biomarkers in AFB1 induced rats. However, a trend for a significant difference was only observed in ALT of AFB1 induced rats treated with LcS compared to their counterparts (126.11 ± 36.90 vs 157.36 ± 15.46, p = 0.06). Rats' body weight decreased in all animals force-fed with AFB1 with no significant difference between LcS treatment compared to the counterpart. In conclusion, this experiment indicated that probiotic LsC was able to slightly ameliorate the adverse effect of an acute exposure to AFB1 in rats. However, future studies with longer probiotics treatment or higher probiotics dose is required to confirm these findings.
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Affiliation(s)
- Elham Nikbakht
- 1 Menzies Health Institute Queensland, School of Medical Science, Griffith University, Gold Coast, Australia
| | - Rosita Jamaluddin
- 2 Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia
| | - S Mohd Redzwan
- 2 Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia
| | - Saman Khalesi
- 3 Physical Activity Research Group, Appleton Institute and School of Health, Medical and Applied Sciences, Central Queensland University, Brisbane, Australia
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32
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Chen Y, Liu Y. Non-coplanar and coplanar polychlorinated biphenyls potentiate genotoxicity of aflatoxin B1 in a human hepatocyte line by enhancing CYP1A2 and CYP3A4 expression. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2019; 246:945-954. [PMID: 31159144 DOI: 10.1016/j.envpol.2018.12.041] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 12/14/2018] [Accepted: 12/14/2018] [Indexed: 06/09/2023]
Abstract
Polychlorinated biphenyls (PCBs) are persistent organic pollutants and hazardous to human health. Aflatoxin B1 (AFB1) is a strong carcinogen dependent on activation by cytochrome P450 (CYP) 1A2 and 3A4. Humans in some regions may be exposed to both PCBs and AFB1. Since PCBs are CYP inducers, we were interested in their combined genotoxicity. In this study, the effects of non-coplanar 2,3,3'-tri- (PCB 20), 2,2'5,5'-tetra- (PCB 52), 2,3,3',4'-tetrachlorobiphenyl (PCB 56), and coplanar 3,3',4,4',5-pentachlorobiphenyl (PCB 126) on protein levels of CYP1A1, 1A2, and 3A4, and nuclear receptors AhR, CAR and PXR in a human hepatocyte (L-02) line were investigated. Moreover, the combined effects of each PCB and AFB1 for induction of micronuclei and double-strand DNA breaks (indicated by an elevation of γ-H2AX) were analyzed. The results indicated that PCBs 20, 52 and 56 reduced the expression of AhR, while elevated that of CAR and PXR, with thresholds at low micromolar concentrations. However, they were less potent than PCB 126, which was active at sub-nanomolar levels. Overexpression of human splice variant CAR 3 in the cells increased CYP1A2 and 3A4 levels, which were further enhanced by each non-coplanar PCB, suggesting a role of CAR in modulating CYPs. Pretreatment of cells with each test PCB potentiated both micronuclei formation and DNA damage induced by AFB1. This study suggests that both non-coplanar and coplanar PCBs may enhance the genotoxicity of AFB1, through acting on various nuclear receptors; the potentiation of AFB1 genotoxicity by PCBs and the potential health implications may deserve concerns and further investigation.
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Affiliation(s)
- Yuting Chen
- Department of Toxicology, School of Public Health, Southern Medical University (Guangdong Provincial Key Laboratory of Tropical Disease Research), 1023 S. Shatai Road, Guangzhou, 510515, China
| | - Yungang Liu
- Department of Toxicology, School of Public Health, Southern Medical University (Guangdong Provincial Key Laboratory of Tropical Disease Research), 1023 S. Shatai Road, Guangzhou, 510515, China.
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Rushing BR, Selim MI. Aflatoxin B1: A review on metabolism, toxicity, occurrence in food, occupational exposure, and detoxification methods. Food Chem Toxicol 2019; 124:81-100. [DOI: 10.1016/j.fct.2018.11.047] [Citation(s) in RCA: 557] [Impact Index Per Article: 92.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Revised: 11/16/2018] [Accepted: 11/19/2018] [Indexed: 12/30/2022]
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Vidal A, Mengelers M, Yang S, De Saeger S, De Boevre M. Mycotoxin Biomarkers of Exposure: A Comprehensive Review. Compr Rev Food Sci Food Saf 2018; 17:1127-1155. [DOI: 10.1111/1541-4337.12367] [Citation(s) in RCA: 130] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2018] [Revised: 05/09/2018] [Accepted: 05/12/2018] [Indexed: 11/30/2022]
Affiliation(s)
- Arnau Vidal
- Laboratory of Food Analysis, Dept. of Bioanalysis, Faculty of Pharmaceutical Sciences; Ghent Univ.; Ghent Belgium
| | - Marcel Mengelers
- Dept. of Food Safety; National Inst. of Public Health and the Environment; Bilthoven The Netherlands
| | - Shupeng Yang
- Inst. of Apicultural Research, Chinese Acad. of Agricultural Sciences, Key Laboratory of Bee Products for Quality and Safety Control, Laboratory of Risk Assessment for Quality and Safety of Bee Products; Bee Product Quality Supervision and Testing Center; Ministry of Agriculture Beijing 100093 People's Republic of China
| | - Sarah De Saeger
- Laboratory of Food Analysis, Dept. of Bioanalysis, Faculty of Pharmaceutical Sciences; Ghent Univ.; Ghent Belgium
| | - Marthe De Boevre
- Laboratory of Food Analysis, Dept. of Bioanalysis, Faculty of Pharmaceutical Sciences; Ghent Univ.; Ghent Belgium
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35
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Oyeyemi O, Ezekiel C, Ayeni K, Nabofa W, Oyeyemi I, Oyedele O, Adefalujo A, Nwozichi C, Dada A. A pilot biomonitoring study of bladder tumor antigen (BTA) in aflatoxin exposed Nigerian villagers. AFRICAN JOURNAL OF UROLOGY 2018; 24:152-156. [DOI: 10.1016/j.afju.2018.02.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Du X, Schrunk DE, Shao D, Imerman PM, Wang C, Ensley SM, Rumbeiha WK. Intra-laboratory Development and Evaluation of a Quantitative Method for Measurement of Aflatoxins B1, M1 and Q1 in Animal Urine by High Performance Liquid Chromatography with Fluorescence Detection. J Anal Toxicol 2017; 41:698-707. [PMID: 28985321 DOI: 10.1093/jat/bkx059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Accepted: 06/28/2017] [Indexed: 11/13/2022] Open
Abstract
Mycotoxins negatively impact animal health. Aflatoxins (AFs) are the most common mycotoxins affecting both large and small animals and are a common cause of toxin-related pet food recalls. Definitive diagnosis of aflatoxicosis is constrained by a lack of validated ante-mortem analytical methods for detection and quantitation of AFs and their metabolites in biological specimens. Herein, we developed and evaluated a urine-based quantitative method for measurement of aflatoxin B1 (AFB1) and its metabolites aflatoxin M1 (AFM1) and aflatoxin Q1 (AFQ1) in animal urine. (Some of the results have been presented at 59th AAVLD conference, Greensboro, North Carolina, October 13-19th, 2016.) This method uses an immuno-affinity column for clean-up and pre-column derivatization followed by high performance liquid chromatography analysis with fluorescence detection. The method has high selectivity, recovery (>81%) and sensitivity with an instrument limit of detection of 0.20-1.02 pg; instrument limit of quantitation of 0.77-4.46 pg; and a method lower limit of quantitation of 0.30-2.5 ng/mL. The method has high accuracy, repeatability, and is rugged against minor changes. However, because of poor sensitivity of AFQ1 at low concentrations we recommend this method for quantitative determination of AFB1 and AFM1, and for qualitative measurement of AFQ1 in animal urine for diagnosis of aflatoxicosis.
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Affiliation(s)
- Xiangwei Du
- Veterinary Diagnostic Laboratory, Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, 1850 Christensen Drive, Ames, IA 50011-1134, USA
| | - Dwayne E Schrunk
- Veterinary Diagnostic Laboratory, Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, 1850 Christensen Drive, Ames, IA 50011-1134, USA
| | - Dahai Shao
- Veterinary Diagnostic Laboratory, Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, 1850 Christensen Drive, Ames, IA 50011-1134, USA
| | - Paula M Imerman
- Veterinary Diagnostic Laboratory, Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, 1850 Christensen Drive, Ames, IA 50011-1134, USA
| | - Chong Wang
- Veterinary Diagnostic Laboratory, Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, 1850 Christensen Drive, Ames, IA 50011-1134, USA
| | - Steve M Ensley
- Veterinary Diagnostic Laboratory, Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, 1850 Christensen Drive, Ames, IA 50011-1134, USA
| | - Wilson K Rumbeiha
- Veterinary Diagnostic Laboratory, Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, 1850 Christensen Drive, Ames, IA 50011-1134, USA
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37
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Ayelign A, Woldegiorgis AZ, Adish A, De Boevre M, Heyndrickx E, De Saeger S. Assessment of aflatoxin exposure among young children in Ethiopia using urinary biomarkers. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2017; 34:1606-1616. [DOI: 10.1080/19440049.2017.1350290] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- Abebe Ayelign
- Department of Bioanalysis, Laboratory of Food Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium
- Center for Food Science and Nutrition, College of Natural Sciences, Addis Ababa University, Addis Ababa, Ethiopia
- Department of Food Science and Postharvest Technology, College of Agriculture and Veterinary Medicine, Jimma University, Jimma, Ethiopia
| | - Ashagrie Zewdu Woldegiorgis
- Center for Food Science and Nutrition, College of Natural Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Abdulaziz Adish
- Micronutrient Initiative (MI), Deputy Regional Director, Addis Ababa, Ethiopia
| | - Marthe De Boevre
- Department of Bioanalysis, Laboratory of Food Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium
| | - Ellen Heyndrickx
- Department of Bioanalysis, Laboratory of Food Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium
| | - Sarah De Saeger
- Department of Bioanalysis, Laboratory of Food Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium
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Determination of aflatoxin M1 in urine samples indicates frequent dietary exposure to aflatoxin B1 in the Bangladeshi population. Int J Hyg Environ Health 2017; 220:271-281. [DOI: 10.1016/j.ijheh.2016.11.002] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Revised: 10/26/2016] [Accepted: 11/07/2016] [Indexed: 11/24/2022]
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Huang L, Duan C, Zhao Y, Gao L, Niu C, Xu J, Li S. Reduction of Aflatoxin B1 Toxicity by Lactobacillus plantarum C88: A Potential Probiotic Strain Isolated from Chinese Traditional Fermented Food "Tofu". PLoS One 2017; 12:e0170109. [PMID: 28129335 PMCID: PMC5271326 DOI: 10.1371/journal.pone.0170109] [Citation(s) in RCA: 67] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2016] [Accepted: 12/29/2016] [Indexed: 01/03/2023] Open
Abstract
In this study, we investigated the potential of Lactobacillus plantarum isolated from Chinese traditional fermented foods to reduce the toxicity of aflatoxin B1 (AFB1), and its subsequent detoxification mechanism. Among all the investigated L. plantarum strains, L. plantarum C88 showed the strongest AFB1 binding capacity in vitro, and was orally administered to mice with liver oxidative damage induced by AFB1. In the therapy groups, the mice that received L. plantarum C88, especially heat-killed L. plantarum C88, after a single dose of AFB1 exposure, showed an increase in unabsorbed AFB1 in the feces. Moreover, the effects of L. plantarum C88 on the enzymes and non-enzymes antioxidant abilities in serum and liver, histological alterations of liver were assayed. The results indicated that compared to the control group, L. plantarum C88 alone administration induced significant increase of antioxidant capacity, but did not induce any significant changes in the histological picture. Compared to the mice that received AFB1 only, L. plantarum C88 treatment could weaken oxidative stress by enhancing the activity of antioxidant enzymes and elevating the expression of Glutathione S-transferase (GST) A3 through Nuclear factor erythroid (derived factor 2) related factor 2 (Nrf2) pathway. Furthermore, cytochrome P450 (CYP 450) 1A2 and CYP 3A4 expression was inhibited by L. plantarum C88, and urinary aflatoxin B1-N7-guanine (AFB-N7-guanine), a AFB1 metabolite formed by CYP 1A2 and CYP 3A4, was significantly reduced by the presence of viable L. plantarum C88. Meanwhile, the significant improvements were showed in histological pictures of the liver tissues in mice orally administered with viable L. plantarum C88. Collectively, L. plantarum C88 may alleviate AFB1 toxicity by increasing fecal AFB1 excretion, reversing deficits in antioxidant defense systems and regulating the metabolism of AFB1.
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Affiliation(s)
- Li Huang
- School of Environment, Northeast Normal University, Changchun, Jilin, The People's Republic of China
| | - Cuicui Duan
- Institute of Agro-food Technology, Jilin Academy of Agricultural Sciences, Changchun, Jilin, The People's Republic of China
| | - Yujuan Zhao
- Institute of Agro-food Technology, Jilin Academy of Agricultural Sciences, Changchun, Jilin, The People's Republic of China
| | - Lei Gao
- Institute of Agro-food Technology, Jilin Academy of Agricultural Sciences, Changchun, Jilin, The People's Republic of China
| | - Chunhua Niu
- Institute of Agro-food Technology, Jilin Academy of Agricultural Sciences, Changchun, Jilin, The People's Republic of China
| | - Jingbo Xu
- School of Environment, Northeast Normal University, Changchun, Jilin, The People's Republic of China
- * E-mail: (JX); (SL)
| | - Shengyu Li
- Institute of Agro-food Technology, Jilin Academy of Agricultural Sciences, Changchun, Jilin, The People's Republic of China
- * E-mail: (JX); (SL)
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40
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Jager AV, Tonin FG, Baptista GZ, Souto PC, Oliveira CA. Assessment of aflatoxin exposure using serum and urinary biomarkers in São Paulo, Brazil: A pilot study. Int J Hyg Environ Health 2016; 219:294-300. [DOI: 10.1016/j.ijheh.2015.12.003] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2015] [Revised: 11/27/2015] [Accepted: 12/14/2015] [Indexed: 10/22/2022]
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41
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Fromme H, Gareis M, Völkel W, Gottschalk C. Overall internal exposure to mycotoxins and their occurrence in occupational and residential settings – An overview. Int J Hyg Environ Health 2016; 219:143-65. [DOI: 10.1016/j.ijheh.2015.11.004] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Revised: 11/12/2015] [Accepted: 11/16/2015] [Indexed: 12/18/2022]
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Effect of supplementation of fermented milk drink containing probiotic Lactobacillus casei Shirota on the concentrations of aflatoxin biomarkers among employees of Universiti Putra Malaysia: a randomised, double-blind, cross-over, placebo-controlled study. Br J Nutr 2015; 115:39-54. [PMID: 26490018 DOI: 10.1017/s0007114515004109] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Human exposure to aflatoxin is through the diet, and probiotics are able to bind aflatoxin and prevent its absorption in the small intestine. This study aimed to determine the effectiveness of a fermented milk drink containing Lactobacillus casei Shirota (LcS) (probiotic drink) to prevent aflatoxin absorption and reduce serum aflatoxin B1-lysine adduct (AFB1-lys) and urinary aflatoxin M1 concentrations. The present study was a randomised, double-blind, cross-over, placebo-controlled study with two 4-week intervention phases. In all, seventy-one subjects recruited from the screening stage were divided into two groups--the Yellow group and the Blue group. In the 1st phase, one group received probiotic drinks twice a day and the other group received placebo drinks. Blood and urine samples were collected at baseline, 2nd and 4th week of the intervention. After a 2-week wash-out period, the treatments were switched between the groups, and blood and urine samples were collected at the 6th, 8th and 10th week (2nd phase) of the intervention. No significant differences in aflatoxin biomarker concentrations were observed during the intervention. A within-group analysis was further carried out. Aflatoxin biomarker concentrations were not significantly different in the Yellow group. Nevertheless, ANOVA for repeated measurements indicated that AFB1-lys concentrations were significantly different (P=0·035) with the probiotic intervention in the Blue group. The 2nd week AFB1-lys concentrations (5·14 (SD 2·15) pg/mg albumin (ALB)) were significantly reduced (P=0·048) compared with the baseline (6·24 (SD 3·42) pg/mg ALB). Besides, the 4th week AFB1-lys concentrations were significantly lower (P<0·05) with probiotic supplementation than with the placebo. Based on these findings, a longer intervention study is warranted to investigate the effects of continuous LcS consumption to prevent dietary aflatoxin exposure.
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43
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Gregorio MCD, Bordin K, Souto PCMDC, Corassin CH, Oliveira CAF. Comparative biotransformation of aflatoxin B1in swine, domestic fowls, and humans. TOXIN REV 2015. [DOI: 10.3109/15569543.2015.1091979] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
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44
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Ali N, Hossain K, Blaszkewicz M, Rahman M, Mohanto NC, Alim A, Degen GH. Occurrence of aflatoxin M1 in urines from rural and urban adult cohorts in Bangladesh. Arch Toxicol 2015; 90:1749-55. [DOI: 10.1007/s00204-015-1601-y] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Accepted: 09/10/2015] [Indexed: 02/04/2023]
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45
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Redzwan SM, Jamaluddin R, Sokhini AM, Aqilah AN, Zuraini A, Karimi G, Parvaneh K. Ultra-high performance liquid chromatographic determination of aflatoxin M1 in urine. WORLD MYCOTOXIN J 2015. [DOI: 10.3920/wmj2014.1761] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The development of analytical methods to detect aflatoxin B1 (AFB1) in foodstuffs and its metabolites in human biological samples is useful for risk assessment. The latter methodology, i.e. the measurement of AFB1 biomarkers, has become important to assess human aflatoxin exposure. AFB1-lysine adduct, AFB1-DNA adduct and urinary aflatoxin M1 (AFM1) are some of the AFB1 biomarkers that can be measured by several analytical methods, such as enzyme-linked immunosorbent assay, radioimmunoassay, and high performance liquid chromatography (HPLC). HPLC coupled to a fluorescence detector is useful and preferable due to its high degree of sensitivity, but the analysis may take time and consume large amount of solvents. Therefore, the present study extrapolated the HPLC method to ultra-HPLC for the determination of urinary AFM1. After the extraction procedure with an immunoaffinity column, chromatographic separation was done using a high performance 1.8 μm microparticulate C18 column. The mean recovery from urine samples spiked with 0.5, 1.0 and 2.0 ng/ml AFM1 was 84.4±4.0%, with acceptable recovery values, interday (6.0±5.3%) and intraday (2.6±0.6%) coefficients of variation. The retention time was 5.7 min. This method was used to measure urinary AFM1 in 71 subjects, of which 13 had AFM1 levels above the limit of detection (0.018 ng/ml). The mean urinary AFM1 level of the positive samples was 18.8±28.6 pg/ml, ranging from 2.4 to 100.4 pg/ml. As this is one of the few studies investigating the occurrence of aflatoxin biomarkers in human biological samples in Malaysia, a study with a larger sample size is necessary to investigate the magnitude of aflatoxin exposure among the population.
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Affiliation(s)
- S. Mohd Redzwan
- Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
| | - R. Jamaluddin
- Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
| | - A.M. Mohd Sokhini
- Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
| | - A.R. Nurul Aqilah
- Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
| | - A. Zuraini
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
| | - G. Karimi
- Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
| | - K. Parvaneh
- Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
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46
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Fast and sensitive LC–MS/MS method measuring human mycotoxin exposure using biomarkers in urine. Arch Toxicol 2014; 89:1993-2005. [DOI: 10.1007/s00204-014-1358-8] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2014] [Accepted: 08/28/2014] [Indexed: 01/11/2023]
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47
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Dohnal V, Wu Q, Kuča K. Metabolism of aflatoxins: key enzymes and interindividual as well as interspecies differences. Arch Toxicol 2014; 88:1635-44. [PMID: 25027283 DOI: 10.1007/s00204-014-1312-9] [Citation(s) in RCA: 178] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2014] [Accepted: 07/02/2014] [Indexed: 11/30/2022]
Abstract
Aflatoxins are potent hepatocarcinogen in animal models and suspected carcinogen in humans. The most important aflatoxin in terms of toxic potency and occurrence is aflatoxin B1 (AFB1). In this review, we mainly summarized the key metabolizing enzymes of AFB1 in animals and humans. Moreover, the interindividual and the interspecies differences in AFB1 metabolism are highly concerned. In human liver, CYP3A4 plays an important role in biotransforming AFB1 to the toxic product AFB1-8,9-epoxide. In human lung, CYP2A13 has a significant activity in metabolizing AFB1 to AFB1-8,9-epoxide and AFM1-8,9-epoxide. The epoxide of AFB1-8,9-epoxide could conjugate with glutathione to reduce the toxicity by glutathione-S-transferase (GST). In poultry species, CYP2A6, CYP3A37, CYP1A5, and CYP1A1 are responsible for bioactivation of AFB1. There are interindividual variations in the rate of activation of aflatoxins in various species, and there are also differences between children and adults. The age and living regions are important factors affecting resistance of species to AFB1. The rate of AFB1-8,9-epoxide formation and its conjugation with glutathione are key parameters in interspecies and interindividual differences in sensitivity to the toxic effect of AFB1. This review provides an important information for key metabolizing enzymes and the global metabolism of aflatoxins in different species.
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Affiliation(s)
- Vlastimil Dohnal
- Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanskeho 62, 500 03, Hradec Kralove, Czech Republic
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48
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Determination of urinary biomarkers for assessment of short-term human exposure to aflatoxins in São Paulo, Brazil. Toxins (Basel) 2014; 6:1996-2007. [PMID: 25007123 PMCID: PMC4113737 DOI: 10.3390/toxins6071996] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2014] [Revised: 06/18/2014] [Accepted: 06/26/2014] [Indexed: 11/16/2022] Open
Abstract
In the present study, a longitudinal assessment was carried out to evaluate the short-term human exposure to aflatoxins in Pirassununga region, São Paulo, Brazil, by determination of urinary aflatoxins by a liquid chromatography coupled to mass sprectrometry (UPLC-MS/MS) method. Sixteen volunteers with ages ranging from 14 to 55 years old were instructed to collect the early morning first urine four times every three months, from June 2011 to March 2012, totaling 64 samples. Aflatoxin M1 (AFM1) was found in 39 samples (61%) at levels ranging from 0.19 to 12.7 pg·mg-1 creatinine (mean: 1.2 ± 2.0 pg·mg-1 creatinine). Residues of aflatoxins B1, B2, G1, G2 and aflatoxicol were not identified in any urine sample. No significant difference was found among the AFM1 mean levels in urine samples collected in the four sampling periods. The levels of AFM1 found in urine samples indicate a low short-term exposure of the population studied to aflatoxins through the diet, although further investigations are needed to assess other long-term biomarkers of exposure to AFB1.
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49
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Turner PC. The molecular epidemiology of chronic aflatoxin driven impaired child growth. SCIENTIFICA 2013; 2013:152879. [PMID: 24455429 PMCID: PMC3881689 DOI: 10.1155/2013/152879] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/18/2013] [Accepted: 10/27/2013] [Indexed: 06/03/2023]
Abstract
Aflatoxins are toxic secondary fungal metabolites that contaminate dietary staples in tropical regions; chronic high levels of exposure are common for many of the poorest populations. Observations in animals indicate that growth and/or food utilization are adversely affected by aflatoxins. This review highlights the development of validated exposure biomarkers and their use here to assess the role of aflatoxins in early life growth retardation. Aflatoxin exposure occurs in utero and continues in early infancy as weaning foods are introduced. Using aflatoxin-albumin exposure biomarkers, five major studies clearly demonstrate strong dose response relationships between exposure in utero and/or early infancy and growth retardation, identified by reduced birth weight and/or low HAZ and WAZ scores. The epidemiological studies include cross-sectional and longitudinal surveys, though aflatoxin reduction intervention studies are now required to further support these data and guide sustainable options to reduce the burden of exposure. The use of aflatoxin exposure biomarkers was essential in understanding the observational data reviewed and will likely be a critical monitor of the effectiveness of interventions to restrict aflatoxin exposure. Given that an estimated 4.5 billion individuals live in regions at risk of dietary contamination the public health concern cannot be over stated.
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Affiliation(s)
- Paul Craig Turner
- Maryland Institute for Applied Environmental Health, School of Public Health, University of Maryland, College Park, MD 20742, USA
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50
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Mohd-Redzwan S, Jamaluddin R, Abd-Mutalib MS, Ahmad Z. A mini review on aflatoxin exposure in Malaysia: past, present and future. Front Microbiol 2013; 4:334. [PMID: 24312084 PMCID: PMC3826065 DOI: 10.3389/fmicb.2013.00334] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2013] [Accepted: 10/22/2013] [Indexed: 01/24/2023] Open
Abstract
This mini review article described the exposure of aflatoxin in Malaysia, including its presence in the foodstuffs and the detection of aflatoxin biomarkers in human biological samples. Historically, the exposure of aflatoxin in Malaysia can be dated in 1960s where an outbreak of disease in pig farms caused severe liver damage to the animals. Later, an aflatoxicosis case in Perak in 1988 was reported and caused death to 13 children, as up to 3 mg of aflatoxin was present in a single serving of contaminated noodles. Since then, extensive research on aflatoxin has been conducted in Malaysia. The food commodities such as peanuts, cereals, spices, and their products are the main commodities commonly found to be contaminated with aflatoxin. Surprisingly, some of the contaminated foods had levels greater than the permissible limit adopted by the Malaysian Food Regulation 1985. Besides, exposure assessment through the measurement of aflatoxin biomarkers in human biological samples is still in its infancy stage. Nevertheless, some studies had reported the presence of these biomarkers. In fact, it is postulated that Malaysians are moderately exposed to aflatoxin compared to those high risk populations, where aflatoxin contamination in the diets is prevalent. Since the ingestion of aflatoxin could be the integral to the development of liver cancer, the incidence of cancer attributable by dietary aflatoxin exposure in Malaysia has also been reported and published in the literatures. Regardless of these findings, the more important task is to monitor and control humans from being exposed to aflatoxin. The enforcement of law is insufficient to minimize human exposure to aflatoxin. Preventive strategies include agricultural, dietary, and clinical measures should be implemented. With the current research on aflatoxin in Malaysia, a global networking for research collaboration is needed to expand the knowledge and disseminate the information to the global scientific community.
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Affiliation(s)
- Sabran Mohd-Redzwan
- Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Serdang, Malaysia
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