AFM1 Exposure in Male Balb/c Mice and Intervention Strategies Against Its Immuno-physiological toxicity using Clay Mineral and Lactic Acid Bacteria Alone or in Combination.

CONTEXT Aflatoxins are the most harmful mycotoxins that cause human and animal health concerns. Aflatoxin M1 (AFM1) is the primary hydroxylated metabolite of aflatoxin B1 and is linked to the development of hepatocellular carcinoma and immunotoxicity in humans and animals. Because of the important role of dairy products in human life, especially children, AFM1 is such a major concern to humans because of its frequent occurrence in dairy products at concentrations high enough to cause adverse effects to human and animal health. Reduced its bioavailability becomes a high priority in order to protect human and animal health. OBJECTIVES This study aimed to investigate, in vivo, the ability of lactic acid bacteria (lactobacillus rhamnosus GAF01, LR) and clay mineral (bentonite, BT) mixture to mitigate/reduce AFM1-induced immunotoxicity, hepatotoxicity, nephrotoxicity and oxidative stress in exposed Balb/c mice. MATERIALS AND METHODS The in vivo study was conducted using male Balb/c mice that treated, orally, by AFM1 alone or in combination with LR and/or BT, daily for 10 days as follows: group 1 control received 200 µl of PBS, group 2 treated with LR alone (2.108 CFU/mL), group 3 treated with BT alone (1g/kg bw), group 4 treated with AFM1 alone (100 μg/kg), group 5 co-treated with LR + AFM1, group 6 co-treated with BT + AFM1, group 7 co-treated with BT + LR + AFM1. Forty-eight h after the end of the treatment, the mice were sacrificed and the blood, spleen, thymus, liver and kidney were collected. The blood was used for biochemical and immunological study. Spleen and thymus samples were used to thymocytes and splenocytes assessments. Liver and kidney samples were the target for evaluation of oxidative stress enzymes status and for histological assays. RESULTS The results showed that AFM1 caused toxicities in male Blab/c mice at different levels. Treatment with AFM1 resulted in severe stress of liver and kidney organs indicated by a significant change in the biochemical and immunological parameters, histopathology as well as a disorder in the profile of oxidative stress enzymes levels. Also, it was demonstrated that AFM1 caused toxicities in thymus and spleen organs. The co-treatment with LR and/or BT significantly improved the hepatic and renal tissues, regulated antioxidant enzyme activities, spleen and thymus viability and biochemical and immunological parameters. LR and BT alone showed to be safe during the treatment. CONCLUSION In summary, the LR and/or BT was able to reduce the biochemical, histopathological and immunological damages induced by AFM1 and indeed it could be exploited as one of the biological strategies for food and feedstuffs detoxification.

[1]  J. Meile,et al.  Occurrence of pre- and postharvest multi-mycotoxins in durum wheat grains collected in 2020 and 2021 in two climatic regions of Tunisia , 2023, Food additives & contaminants. Part B, Surveillance.

[2]  J. Meile,et al.  Prevention and Detoxification of Mycotoxins in Human Food and Animal Feed using Bio-resources from South Mediterranean Countries: a Critical Review , 2023, Critical reviews in toxicology.

[3]  Lijun Sun,et al.  Removal of aflatoxin b1 and t-2 toxin by bacteria isolated from commercially available probiotic dairy foods , 2021, Food science and technology international = Ciencia y tecnologia de los alimentos internacional.

[4]  Jalila ben Salah-Abbès,et al.  Lactobacillus paracasei alleviates genotoxicity, oxidative stress status and histopathological damage induced by Fumonisin B1 in BALB/c mice. , 2020, Toxicon : official journal of the International Society on Toxinology.

[5]  B. Buszewski,et al.  Use of Lactobacillus paracasei strain for zearalenone binding and metabolization. , 2020, Toxicon : official journal of the International Society on Toxinology.

[6]  L. Csernoch,et al.  Toxicological and Medical Aspects of Aspergillus-Derived Mycotoxins Entering the Feed and Food Chain , 2020, Frontiers in Microbiology.

[7]  D. Asker,et al.  Characterization of antifungal metabolites produced by novel lactic acid bacterium and their potential application as food biopreservatives , 2019, Annals of Agricultural Sciences.

[8]  A. Atoui,et al.  Assorted Methods for Decontamination of Aflatoxin M1 in Milk Using Microbial Adsorbents , 2019, Toxins.

[9]  Jalila ben Salah-Abbès,et al.  Lactobacillus plantarum MON03 counteracts zearalenone génotoxicty in mice: Chromosome aberrations, micronuclei, DNA fragmentation and apoptotique gene expression. , 2019, Mutation research. Genetic toxicology and environmental mutagenesis.

[10]  M. Selim,et al.  Aflatoxin B1: A review on metabolism, toxicity, occurrence in food, occupational exposure, and detoxification methods. , 2019, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[11]  Mustafa A. Fawzy,et al.  Use of seaweed and filamentous fungus derived polysaccharides in the development of alginate-chitosan edible films containing fucoidan: Study of moisture sorption, polyphenol release and antioxidant properties , 2018, Food Hydrocolloids.

[12]  Gang Qian,et al.  Immunotoxicity of ochratoxin A and aflatoxin B1 in combination is associated with the nuclear factor kappa B signaling pathway in 3D4/21 cells. , 2018, Chemosphere.

[13]  M. Theumer,et al.  Genotoxicity of aflatoxins and their precursors in human cells. , 2018, Toxicology letters.

[14]  M. Bryła,et al.  Modified Fusarium Mycotoxins in Cereals and Their Products—Metabolism, Occurrence, and Toxicity: An Updated Review , 2018, Molecules.

[15]  B. Buszewski,et al.  Microbiology neutralization of zearalenone using Lactococcus lactis and Bifidobacterium sp. , 2017, Analytical and Bioanalytical Chemistry.

[16]  J. L. Gonçalves,et al.  Effects of different sources of Saccharomyces cerevisiae biomass on milk production, composition, and aflatoxin M1 excretion in milk from dairy cows fed aflatoxin B1. , 2017, Journal of dairy science.

[17]  N. Kurrey,et al.  Protective effects of phenolics rich extract of ginger against Aflatoxin B1-induced oxidative stress and hepatotoxicity. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[18]  Amal S. Hathout,et al.  Evaluation of the bioactive extract of actinomyces isolated from the Egyptian environment against aflatoxin B1-induce cytotoxicity, genotoxicity and oxidative stress in the liver of rats. , 2017, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[19]  S. Hashemi,et al.  Antifungal Activity and Aflatoxin Degradation of Bifidobacterium Bifidum and Lactobacillus Fermentum Against Toxigenic Aspergillus Parasiticus , 2016, The open microbiology journal.

[20]  Daniel Granato,et al.  The occurrence and effect of unit operations for dairy products processing on the fate of aflatoxin M1: A review , 2016 .

[21]  M. Ibrahim,et al.  Curcumin nanoparticles loaded hydrogels protects against aflatoxin B1-induced genotoxicity in rat liver. , 2016, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[22]  C. Ji,et al.  Review on biological degradation of mycotoxins , 2016, Animal nutrition.

[23]  S. El-Bahr,et al.  Effect of Curcumin on Hepatic Antioxidant Enzymes Activities and Gene Expressions in Rats Intoxicated with Aflatoxin B1 , 2015, Phytotherapy research : PTR.

[24]  Z. Zuo,et al.  Protective Roles of Sodium Selenite against Aflatoxin B1-Induced Apoptosis of Jejunum in Broilers , 2014, International journal of environmental research and public health.

[25]  Y. Mine,et al.  In vitro and ex vivo uptake of glutathione (GSH) across the intestinal epithelium and fate of oral GSH after in vivo supplementation. , 2014, Journal of agricultural and food chemistry.

[26]  M. Ramadan,et al.  Detoxification of aflatoxin M1 in yoghurt using probiotics and lactic acid bacteria , 2014 .

[27]  S. Roussos,et al.  Lactic acid bacteria against post-harvest moulds and ochratoxin A isolated from stored wheat , 2014 .

[28]  Jianyun Zhang,et al.  Effects of Lipoic Acid on Immune Function, the Antioxidant Defense System, and Inflammation-Related Genes Expression of Broiler Chickens Fed Aflatoxin Contaminated Diets , 2014, International journal of molecular sciences.

[29]  E. Arendt,et al.  Cereal fungal infection, mycotoxins, and lactic acid bacteria mediated bioprotection: from crop farming to cereal products. , 2014, Food microbiology.

[30]  F. Tateo,et al.  Clay minerals as adsorbents of aflatoxin M1 from contaminated milk and effects on milk quality , 2014 .

[31]  Fernanda Bovo,et al.  Efficiency of Lactic Acid Bacteria Strains for Decontamination of Aflatoxin M1 in Phosphate Buffer Saline Solution and in Skimmed Milk , 2013, Food and Bioprocess Technology.

[32]  K. A. Noghabi,et al.  Lactobacillus paracasei BEJ01 prevents immunotoxic effects during chronic zearalenone exposure in Balb/c mice , 2013, Immunopharmacology and immunotoxicology.

[33]  M. Parsi,et al.  Aflatoxins, hepatocellular carcinoma and public health. , 2013, World journal of gastroenterology.

[34]  K. A. Noghabi,et al.  Interaction of Lactobacillus plantarum MON03 with Tunisian Montmorillonite clay and ability of the composite to immobilize Zearalenone in vitro and counteract immunotoxicity in vivo , 2012, Immunopharmacology and immunotoxicology.

[35]  Z. Emam-djomeh,et al.  Evaluation of aflatoxin decontaminating by two strains of Saccharomyces cerevisiae and Lactobacillus rhamnosus strain GG in pistachio nuts , 2012 .

[36]  R. Oueslati,et al.  Natural occurrence of aflatoxins (B1 and M1) in feed, plasma and raw milk of lactating dairy cows in Beja, Tunisia, using ELISA , 2012, Food additives & contaminants. Part B, Surveillance.

[37]  C. Amiama,et al.  Estimating efficiency in automatic milking systems. , 2012, Journal of dairy science.

[38]  Amal S. Hathout,et al.  Ability of Lactobacillus casei and Lactobacillus reuteri to protect against oxidative stress in rats fed aflatoxins-contaminated diet. , 2011, Toxicon : official journal of the International Society on Toxinology.

[39]  Y. Jang,et al.  Inhibitory effects of quercetin on aflatoxin B1-induced hepatic damage in mice. , 2010, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[40]  F. Richard-Forget,et al.  Lactic acid bacteria – Potential for control of mould growth and mycotoxins: A review , 2010 .

[41]  Y. Khadrawy,et al.  Red ginseng extract protects against aflatoxin B1 and fumonisins-induced hepatic pre-cancerous lesions in rats. , 2010, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[42]  S. Lecoeur,et al.  Metabolism and transfer of the mycotoxin zearalenone in human intestinal Caco-2 cells. , 2008, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[43]  R. Oueslati,et al.  Preventive role of aluminosilicate clay against induction of micronuclei and chromosome aberrations in bone-marrow cells of Balb/c mice treated with Zearalenone. , 2007, Mutation research.

[44]  D. Morgavi,et al.  Binding of Fusarium mycotoxins by fermentative bacteria in vitro , 2006, Journal of applied microbiology.

[45]  Douglas L. Park,et al.  Workgroup Report: Public Health Strategies for Reducing Aflatoxin Exposure in Developing Countries , 2006, Environmental health perspectives.

[46]  R. Oueslati,et al.  Preventive role of phyllosilicate clay on the Immunological and Biochemical toxicity of zearalenone in Balb/c mice. , 2006, International immunopharmacology.

[47]  R. Oueslati,et al.  The protective effect of hydrated sodium calcium aluminosilicate against haematological, biochemical and pathological changes induced by Zearalenone in mice. , 2006, Toxicon : official journal of the International Society on Toxinology.

[48]  S. Aly,et al.  Antioxidant property of Nigella sativa (black cumin) and Syzygium aromaticum (clove) in rats during aflatoxicosis , 2005, Journal of applied toxicology : JAT.

[49]  S. Lahtinen,et al.  Binding of aflatoxin B1 to cell wall components of Lactobacillus rhamnosus strain GG , 2004, Food additives and contaminants.

[50]  G. Widmalm,et al.  Structural studies of the exopolysaccharide produced by Lactobacillus rhamnosus strain GG (ATCC 53103). , 2002, Biomacromolecules.

[51]  F. Yu,et al.  The effects of mycotoxins, fumonisin B1 and aflatoxin B1, on primary swine alveolar macrophages. , 2002, Toxicology and applied pharmacology.

[52]  T. Phillips,et al.  Dietary clay in the chemoprevention of aflatoxin-induced disease. , 1999, Toxicological sciences : an official journal of the Society of Toxicology.

[53]  K. Yagi,et al.  A simple fluorometric assay for lipoperoxide in blood plasma. , 1976, Biochemical medicine.

[54]  S. Marklund,et al.  Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. , 1974, European journal of biochemistry.

[55]  K. Keener,et al.  A review of novel physical and chemical decontamination technologies for aflatoxin in food , 2018 .

[56]  Juan Carlos Moltó,et al.  Review on the toxicity, occurrence, metabolism, detoxification, regulations and intake of zearalenone: an oestrogenic mycotoxin. , 2007, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[57]  Xiangke Wang,et al.  Diffusion and sorption of U(VI) in compacted bentonite studied by a capillary method , 2005 .

[58]  J. Sedlák,et al.  Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. , 1968, Analytical biochemistry.