Abstract
Fungi and their mycotoxins are ubiquitous, contaminating the air we breathe and the food we eat on a daily basis. Mycotoxins are considered a natural and unavoidable contaminant of food crops. Anthropogenic climate change is anticipated to increase mycotoxin contamination. Although mycotoxins are too small to be seen by the naked eye, uncontrolled mycotoxins can cause gangrene, miscarriage, cancer, and death. Mycotoxins in low amounts stimulate an immune response from macrophages. Mycotoxins in high amounts shut down the immune response preventing an adequate defence. Fumigaclavine C reduces toll-like receptor 4 expression and tumor necrosis factor alpha. Aflatoxins are carcinogenic and have been linked to tumor formation in the colon, kidneys, liver, and lungs. Aflatoxin B1 is the strongest carcinogen of all the aflatoxins. Aflatoxin B1 is removed by macrophage autophagy and by extracellular traps. Ochratoxin A has been found to be nephrotoxic, teratogenic, carcinogenic, and immunotoxic. Ochratoxin A acts as a competitive inhibitor for phenylalanine-tRNA synthetase which halts protein synthesis. Ochratoxin A’s effects can be blocked by phenylalanine. Trichothecene mycotoxins are lethal enough to be utilized as biological chemical warfare agents, and they have been. Mycotoxins act synergistically with other mycotoxins, bacterial endotoxin, and virus causing a greater adverse effect than the sum of their individual effects. Synergy helps to explain the observed effects of damp building-related illness. Controlled amounts of specific mycotoxins can be clinically useful. Ergometrine has been used clinically to stimulate uterine contractions in order to induce childbirth. After child delivery, ergometrine can be used to help control bleeding via its vasoconstrictive action. Ergotamine has been used clinically to reduce pain associated with migraine headaches. The immunosuppressant activity of mycophenolic acid arises from its ability to reversibly inhibit the enzyme inosine 5′-monophosphate dehydrogenase thereby shutting down the biochemical de novo pathway which synthesizes guanine nucleotides. The immunosuppressive effects of mycophenolic acid have found utility in treating autoimmune diseases of rheumatoid arthritis and lupus nephritis. Mycophenolic acid helps prevent organ transplant rejection for kidney, heart, and liver recipients.
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References
Alshannaq A, Yu JH. Occurrence, toxicity, and analysis of major mycotoxins in food. Int J Environ Res Pub Health. 2017;14(6):632.
An Y, Shi X, Tang X, et al. Aflatoxin B1 induces reactive oxygen species-mediated autophagy and extracellular trap formation in macrophages. Front Cell Infect Microbiol. 2017;7:53.
Aronson JK. Plant poisons and traditional medicines. In: Farrar J, Hotez PJ, Junghanss T, Kang G, Lalloo D, White NJ, editors. Manson’s tropical infectious diseases. 23rd ed. W.B. Saunders; 2014. p. 1128–50.
Bardal SK, Waechter JE, Martin DS. Neurology and the neuromuscular system. In: Bardal SK, Martin DS, Waechter JE, editors. Applied pharmacology. St. Louis: Elsevier Saunders; 2011. p. 325–65.
Barrett JR. Mycotoxins: of molds and maladies. Environ Health Perspect. 2000;108(1):A20–3.
Behrend M. Mycophenolate mofetil: suggested guidelines for use in kidney transplantation. BioDrugs. 2001;15(1):37–53.
Belmont HM, Levartovsky D, Goel A, et al. Increased nitric oxide production accompanied by the up-regulation of inducible nitric oxide synthase in vascular endothelium from patients with systemic lupus erythematosus. Arthritis Rheum. 1997;40(10):1810–6.
Belser-Ehrlich S, Harper A, Hussey J, Hallock R. Human and cattle ergotism since 1900: symptoms, outbreaks, and regulations. Toxicol Ind Health. 2013;29(4):307–16.
Boorman GA, Hong HL, Dieter MP, et al. Myelotoxicity and macrophage alteration in mice exposed to ochratoxin A. Toxicol Appl Pharmacol. 1984;72:304–12.
Borroto-Esoda K, Myrick F, Feng J, Jeffrey J, Furman P. In vitro combination of amdoxovir and the inosine monophosphate dehydrogenase inhibitors mycophenolic acid and ribavirin demonstrates potent activity against wild-type and drug-resistant variants of human immunodeficiency virus type 1. Antimicrob Agents Chemother. 2004;48(11):4387–94.
Bui-Klimke TR, Wu F. Ochratoxin A and human health risk: a review of the evidence. Crit Rev Food Sci Nutr. 2015;55(13):1860–9.
Chan TM, Li FK, Tang CSO, et al. Efficacy of mycophenolate Mofetil in patients with diffuse proliferative lupus nephritis. N Engl J Med. 2000;343:1156–62.
Coffel ED, Horton RM, Sherbinin A. Temperature and humidity based projections of a rapid rise in global heat stress exposure during the 21st century. Environ Res Lett. 2018;13:014001.
Creppy EE, Lugnier AAJ, Beck G, Röschenthaler R, Dirheimer G. Action of Ochratoxin A on cultured hepatoma cells reversion of inhibition by phenylalanine. FEBS Lett. 1979;104:287–90.
Creppy EE, Schlegel M, Röschenthaler R, Dirheimer G. Phenylalanine prevents acute poisoning by Ochratoxin A in mice. Toxicol Lett. 1980;6:77–80.
Desaint H, Aoun N, Deslandes L, Vailleau F, Roux F, Berthome R. Fight hard or die trying: when plants face pathogens under heat stress. New Phytol. 2021;229(2):712–34.
Du RH, Li EG, Cao Y, Song YC, Tan RX. Fumigaclavine C inhibits tumor necrosis factor α production via suppression of toll-like receptor 4 and nuclear factor κB activation in macrophages. Life Sci. 2011;89(7-8):235–40.
Ferrante MC, MattaceRaso G, Bilancione M, Esposito E, Iacono A, Meli R. Differential modification of inflammatory enzymes in J774A.1 macrophages by Ochratoxin A alone or in combination with lipopolysaccharide. Toxicol Lett. 2008;181(1):40–6.
Goldblum R. Therapy of rheumatoid arthritis with mycophenolate mofetil. Clin Exp Rheumatol. 1993;11(Suppl 8):S117–9.
Haarmann T, Rolke Y, Giesbert S, Tudzynski P. Ergot: from witchcraft to biotechnology. Mol Plant Pathol. 2009;10(4):563–77.
Haschek WM, Beasley VR. Trichothecene Mycotoxins. In: Gupta RC, editor. Handbook of toxicology of chemical warfare agents. Academic Press; 2009. p. 353–69.
Haubeck HD, Lorkowski G, Kölsch E, Röschenthaler R. Immunosuppression by Ochratoxin A and its prevention by phenylalanine. Appl Environ Microbiol. 1981;41(4):1040–2.
Hogquist KA, Unanue ER, Chaplin DD. Release of IL-1 from mononuclear phagocytes. J Immunol. 1991;147(7):2181–6.
Holstege CP, Traven SA. Ergot. In: Wexler P, editor. Encyclopedia of toxicology. 3rd ed. Academic Press; 2014. p. 444–7.
Islam Z, Pestka JJ. LPS priming potentiates and prolongs proinflammatory cytokine response to the trichothecene deoxynivalenol in the mouse. Toxicol Appl Pharmacol. 2006;211(1):53–63.
Jonsson CA, Carlsten H. Mycophenolic acid inhibits inosine 5′-monophosphate dehydrogenase and suppresses production of pro-inflammatory cytokines, nitric oxide, and LDH in macrophages. Cell Immunol. 2002;216(1-2):93–101.
Kankkunen P, Rintahaka J, Aalto A, et al. Trichothecene Mycotoxins activate inflammatory response in human macrophages. J Immunol. 2009;182(10):6418–25.
Kew MC. Synergistic interaction between aflatoxin B1 and hepatitis B virus in hepatocarcinogenesis. Liver Int. 2003;23(6):405–9.
Lindenfelser LA, Lillehoj EB, Burmeister HR. Aflatoxin and Trichothecene toxins: skin tumor induction and synergistic acute toxicity in white mice. J Natl Cancer Inst. 1974;52(1):113–6.
Madsen A, Mortensen HP, Hald B. Feeding experiments with ochratoxin A contaminated barley for bacon pigs I. influence on pig performance and residues. Acta Agric Scand. 1982;32:225–39.
Mitchell CG, Slight J, Donaldson K. Diffusible component from the spore surface of the fungus Aspergillus fumigatus which inhibits the macrophage oxidative burst is distinct from gliotoxin and other hyphal toxins. Thorax. 1997;52:796–801.
Morabia A. Joseph Goldberger’s research on the prevention of pellagra. J R Soc Med. 2008;101(11):566–8.
Müller G, Rosner H, Rohrmann B, et al. Effects of the mycotoxin Ochratoxin A and some of its metabolites on the human cell line THP-1. Toxicology. 2003;184(1):69–82.
National Center for Biotechnology Information. PubChem compound summary for CID 5281078, Mycophenolate mofetil. 2021. https://pubchem.ncbi.nlm.nih.gov/compound/Mycophenolate-mofetil
Online Etymology Dictionary.. https://www.etymonline.com/word/ergot
Paulussen C, Hallsworth JE, Alvarez-Perez S, et al. Ecology of aspergillosis: insights into the pathogenic potency of Aspergillus fumigatus and some other Aspergillus species. Microbial Biotechnol. 2017;10(2):296–322.
Pestka JJ, Yike I, Dearborn DG, Ward MD, Harkema JR. Stachybotrys chartarum, trichothecene mycotoxins, and damp building-related illness: new insights into a public health enigma. Toxicol Sci. 2008;104(1):4–26.
Regueira TB, Kildegaard KR, Hansen BG, Mortensen UH, Hertweck C, Nielsen J. Molecular basis for Mycophenolic acid biosynthesis in Penicillium brevicompactum. Appl Environ Microbiol. 2011;77(9):3035–43.
Robertson MD, Seaton A, Raeburn A, Milne LJR. Inhibition of phagocyte migration and spreading by spore diffusates of Aspergillus fumigatus. J Med Vet Mycol. 1987a;25(6):389–96.
Robertson MD, Seaton A, Milne LJ, Raeburn JA. Suppression of host defences by Aspergillus fumigatus. Thorax. 1987b;42(1):19–25.
Robertson MD, Seaton A, Milne LJR, Raeburn A. Resistance of spores of Aspergillus fumigatus to ingestion by phagocytic cells. Thorax. 1987c;42:466–72.
Shiva S. Nitrite: A physiological store of nitric oxide and modulator of mitochondrial function. Redox Biol. 2013;1(1):40–4.
Sokoloski JA, Blair OC, Salterelli AC. Alterations in glycoprotein synthesis and guanosine triphosphate levels associated with the differentiation of HL-60 leukemia cells produced by inhibitors of inosine 5′-phosphate dehydrogenase. Cancer Res. 1986;46:2314–9.
Special Report No. 104 United States Department of State Chemical Warfare in Southeast Asia and Afghanistan: An Update Report from Secretary of State George P. Shultz November 1982. http://insidethecoldwar.org/sites/default/files/documents/Chemical%20Warfare%20in%20Southeast%20Asia%20and%20Afghanistan%20an%20Update%20November%201982.pdf
Squire RA. Ranking animal carcinogens: a proposed regulatory approach. Science. 1981;214:877–80.
United States Environmental Protection Agency A Brief Guide to Mold, Moisture and Your Home. https://www.epa.gov/mold/brief-guide-mold-moisture-and-your-home
United States Environmental Protection Agency Mold Course Chapter 1: Introduction to Molds. https://www.epa.gov/mold/mold-course-chapter-1
Wang H, Yadav JS. DNA damage, redox changes, and associated stress-inducible signaling events underlying the apoptosis and cytotoxicity in murine alveolar macrophage cell line MH-S by methanol-extracted Stachybotrys chartarum toxins. Toxicol Appl Pharmacol. 2006;214(3):297–308.
Wang H, Yadav JS. Global gene expression changes underlying Stachybotrys chartarum toxin-induced apoptosis in murine alveolar macrophages: Evidence of multiple signal transduction pathways. Apoptosis. 2007;12:535–48.
Yagen B, Joffe AZ. Screening of toxic isolates of Fusarium poae and Fusarium sporotrichioides involved in causing alimentary toxic aleukia. Appl Environ Microbiol. 1976;32(3):423–7.
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Cleary, D. (2022). Effects of Mycotoxins on Macrophages and Their Possible Clinical Implications. In: Gupta, S., Pathak, Y.V. (eds) Macrophage Targeted Delivery Systems. Springer, Cham. https://doi.org/10.1007/978-3-030-84164-5_23
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