Immunotoxic activity of ochratoxin A.

Ochratoxin A (OTA) is an immunosuppressant fungal compound, produced by toxigenic species of Aspergillus and Penicillium fungi in a wide variety of climates and geographical regions. The contamination of food by this mycotoxin takes place primarily during preharvest periods. Almost all types of food can be contaminated. In addition, its chemical stability against heat and during industrial food processing makes OTA one of the most abundant food contaminating mycotoxins. Due in part to its long serum half-life in man, almost 100% of all human blood samples from some geographic regions may be positive for OTA. The immunosuppressant activity of OTA is characterized by size reduction of vital immune organs, such as thymus, spleen, and lymph nodes, depression of antibody responses, alterations in the number and functions of immune cells, and modulation of cytokine production. The immunotoxic activity of OTA probably results from degenerative changes and cell death following necrosis and apoptosis, in combination with slow replacement of affected immune cells, due to inhibition of protein synthesis.

[1]  R. Harvey,et al.  Immunotoxicity of ochratoxin A to growing gilts. , 1992, American journal of veterinary research.

[2]  F. Fasiolo,et al.  In vitro inhibition of yeast phenylalanyl-tRNA synthetase by ochratoxin A. , 1979, Chemico-Biological Interactions.

[3]  Roland Diller,et al.  Effects of the mycotoxin ochratoxin A and some of its metabolites on the human cell line THP-1. , 2003, Toxicology.

[4]  L. Al-Anati,et al.  Interference of arachidonic acid and its metabolites with TNF-alpha release by ochratoxin A from rat liver. , 2005, Toxicology.

[5]  E. Petzinger,et al.  Mycotoxins in the food chain: the role of ochratoxins , 2002 .

[6]  E. González-Peñas,et al.  Contribution to the study of ochratoxin A in Spanish wines , 2002, Food additives and contaminants.

[7]  G. Rottinghaus,et al.  Administration of ochratoxin A and T-2 toxin to growing swine. , 1994, American journal of veterinary research.

[8]  M. F. Ackermann,et al.  Selective immunosuppression in mice of natural killer cell activity by ochratoxin A. , 1987, Cancer research.

[9]  G. Hartmann,et al.  Specific type IV phosphodiesterase inhibitor rolipram mitigates experimental colitis in mice. , 1998, The Journal of pharmacology and experimental therapeutics.

[10]  E. Petzinger,et al.  Ochratoxin A from a toxicological perspective. , 2000, Journal of veterinary pharmacology and therapeutics.

[11]  S. Endres,et al.  The specific type IV phosphodiesterase inhibitor rolipram suppresses tumor necrosis factor-alpha production by human mononuclear cells. , 1993, International journal of immunopharmacology.

[12]  M. Prior,et al.  The effects of ochratoxin A on the immune response of Swiss mice. , 1982, Canadian journal of comparative medicine : Revue canadienne de medecine comparee.

[13]  M. Pitout,et al.  The inhibitory effect of ochratoxin A on bovine carboxypeptidase A in vitro. , 1969, Biochemical pharmacology.

[14]  D. Kern,et al.  Effects of ochratoxin A metabolites on yeast phenylalanyl-tRNA synthetase and on the growth and in vivo protein synthesis of hepatoma cells. , 1983, Chemico-biological interactions.

[15]  P. Mantle,et al.  Susceptibility to secondary bacterial infections in growing pigs as an early response in ochratoxicosis. , 2000, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[16]  H. Köhler,et al.  Studies of the influence of ochratoxin A on immune and defence reactions in the mouse model , 1995, Mycoses.

[17]  M. Pallardy,et al.  Ochratoxin A induces apoptosis in human lymphocytes through down regulation of Bcl-xL. , 2004, Toxicological sciences : an official journal of the Society of Toxicology.

[18]  A. Breitholtz-Emanuelsson,et al.  Prenatal exposure of Balb/c mice to ochratoxin A: effects on the immune system in the offspring. , 1996, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[19]  R. Guy,et al.  Fate of ochratoxin A in the processing of whole wheat grain during extrusion , 2004, Food additives and contaminants.

[20]  P. Galtier,et al.  The pharmacokinetic profiles of ochratoxin A in pigs, rabbits and chickens. , 1981, Food and cosmetics toxicology.

[21]  P. Galtier Contribution of pharmacokinetic studies to mycotoxicology—Ochratoxin A , 1977, Veterinary Science Communications.

[22]  A. Lucic,et al.  Ochratoxin A-induced apoptosis in rat kidney tissue. , 2004, Arhiv za higijenu rada i toksikologiju.

[23]  D. Corrier Mycotoxicosis: mechanisms of immunosuppression. , 1991, Veterinary immunology and immunopathology.

[24]  P. Krogh,et al.  Phosphoenolpyruvate carboxykinase as a selective indicator of ochratoxin A induced nephropathy. , 1986, Developments in toxicology and environmental science.

[25]  P. Mantle,et al.  Clinicomorphological Studies in Chicks Fed Ochratoxin A While Simultaneously Developing Coccidiosis , 2002, Veterinary Research Communications.

[26]  Y. Kozuka,et al.  Histopathological studies on the toxicity of ochratoxin A in rats. I. Acute oral toxicity. , 1977, Toxicology and applied pharmacology.

[27]  R. R. Marquardt,et al.  A review of recent advances in understanding ochratoxicosis. , 1992, Journal of animal science.

[28]  R. Harvey,et al.  Immunologic effects of low levels of ochratoxin A in ovo: utilization of a chicken embryo model. , 1987, Avian diseases.

[29]  T. Lea,et al.  Mechanism of ochratoxin A-induced immunosuppression , 1989, Mycopathologia.

[30]  B. Rohrmann,et al.  In vitro-Untersuchungen zum Einfluss von Ochratoxin A auf die Tumornekrosefaktor aplha-Produktion der humanen Monozytenzelllinie THP 1 , 2002 .

[31]  R. Burns,et al.  Pathology of ochratoxicosis A in young broiler chicks. , 1984, Research in veterinary science.

[32]  A. Breitholtz-Emanuelsson,et al.  Effects of ochratoxin A on the mouse immune system after subchronic exposure. , 1995, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[33]  B. K. Swain,et al.  Effect of graded levels of aflatoxin, ochratoxin and their combinations on the performance and immune response of broilers , 2004, British poultry science.

[34]  Raghubir P. Sharma,et al.  Immunotoxicity of mycotoxins. , 1993, Journal of dairy science.

[35]  G. Boorman,et al.  Residual hematopoietic effect in mice exposed to ochratoxin A prior to irradiation. , 1988, Toxicology.

[36]  J. Molnár,et al.  Effects of mycotoxins on human immune functions in vitro. , 2001, Toxicology in vitro : an international journal published in association with BIBRA.

[37]  P. Hamilton,et al.  Impairment of phagocytosis by heterophils from chickens during ochratoxicosis , 1980, Applied and environmental microbiology.

[38]  R. Hanson,et al.  Decrease of renal phosphoenolpyruvate carboxykinase RNA and poly(A)+ RNA level by ochratoxin A. , 1983, Archives of biochemistry and biophysics.

[39]  J. Schlatter,et al.  Ochratoxin A: induction of (oxidative) DNA damage, cytotoxicity and apoptosis in mammalian cell lines and primary cells. , 2005, Toxicology.

[40]  D. Patterson,et al.  Effect on calves of barley naturally contaminated with ochratoxin A and groundnut meal contaminated with low concentrations of aflatoxin B1. , 1981, Research in veterinary science.

[41]  H. Köhler,et al.  Studies of the influence of ochratoxin A on immune and defence reactions in weaners , 1999, Mycoses.

[42]  K. Singh,et al.  Immunosuppression due to chronic ochratoxicosis in broiler chicks. , 1990, Journal of comparative pathology.

[43]  P. Hamilton,et al.  Natural occurrences of ochratoxicosis in poultry. , 1982, Poultry science.

[44]  A. Oskarsson,et al.  Effects of ochratoxin A on the rat immune system after perinatal exposure. , 1996, Natural toxins.

[45]  E. Çiçek,et al.  Histopathologic changes in liver and renal tissues induced by Ochratoxin a and melatonin in rats , 2003, Human & experimental toxicology.

[46]  H. van Loveren,et al.  Age-related differences in the toxicity of ochratoxin A in female rats. , 2001, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[47]  E. González-Peñas,et al.  Exposure to Ochratoxin a in Europe: Comparison with a Region of Northern Spain , 1998 .

[48]  R. Manderville,et al.  Evidence for covalent DNA adduction by ochratoxin A following chronic exposure to rat and subacute exposure to pig. , 2004, Chemical research in toxicology.

[49]  Y. Wei,et al.  Effect of ochratoxin A on rat liver mitochondrial respiration and oxidative phosphorylation. , 1985, Toxicology.

[50]  T. Lea,et al.  Effects of ochratoxin A upon early and late events in human T-cell proliferation. , 1995, Toxicology.

[51]  J. Pelkonen,et al.  Synergistic interaction in simultaneous exposure to Streptomyces californicus and Stachybotrys chartarum. , 2004, Environmental health perspectives.

[52]  P. Hamilton,et al.  A leucocytopenia induced in chickens by dietary ochratoxin A. , 1979, Poultry science.

[53]  F. Galvano,et al.  Effects of rosmarinic acid against aflatoxin B1 and ochratoxin‐A‐induced cell damage in a human hepatoma cell line (Hep G2) , 2004, Journal of applied toxicology : JAT.

[54]  James L. Baker,et al.  Ochratoxin Production by the Aspergillus ochraceus Group and Aspergillus alliaceus , 2002, Applied and Environmental Microbiology.

[55]  I. Studer-Rohr,et al.  Kinetic parameters and intraindividual fluctuations of ochratoxin A plasma levels in humans , 2000, Archives of Toxicology.

[56]  E. Creppy,et al.  Phenylalanine prevents acute poisoning by ochratoxina in mice. , 1980, Toxicology letters.

[57]  M. Peraica,et al.  Spontaneous mycotoxic nephropathy in Bulgarian chickens with unclarified mycotoxin aetiology. , 2002, Veterinary research.

[58]  I. Ivanov,et al.  Influence of ochratoxin A and an extract of artichoke on the vaccinal immunity and health in broiler chicks. , 2000, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[59]  A. Kanthasamy,et al.  Ochratoxin A toxicity on carbohydrate metabolism in rats , 1989, Bulletin of Environmental Contamination and Toxicology.

[60]  S. Silbernagl,et al.  The nephrotoxin ochratoxin A induces apoptosis in cultured human proximal tubule cells , 2004, Cell Biology and Toxicology.

[61]  H. Okutan,et al.  Protective role of melatonin in ochratoxin a toxicity in rat heart and lung , 2004, Journal of applied toxicology : JAT.

[62]  D. Ledoux,et al.  Pathological changes in broiler chickens fed ochratoxin A and inoculated with Escherichia coli , 2004, Avian pathology : journal of the W.V.P.A.

[63]  J. Pestka,et al.  Effects of mycotoxins on cytokine production and proliferation in EL-4 thymoma cells. , 1996, Journal of toxicology and environmental health.

[64]  R. Walker Risk assessment of ochratoxin: current views of the European Scientific Committee on Food, the JECFA and the Codex Committee on Food Additives and Contaminants. , 2002, Advances in experimental medicine and biology.

[65]  P. Scott,et al.  Risk assessment of the mycotoxin ochratoxin A. , 1989, Biomedical and environmental sciences : BES.

[66]  E. Creppy,et al.  Combined action of citrinin and ochratoxin A on hepatoma tissue culture cells. , 1980, Toxicology letters.

[67]  S. Mildenberger,et al.  Ochratoxin A induces JNK activation and apoptosis in MDCK-C7 cells at nanomolar concentrations. , 2000, The Journal of pharmacology and experimental therapeutics.

[68]  A. Breitholtz-Emanuelsson,et al.  Influence of perinatal ochratoxin A exposure on the immune system in mice. , 1996, Natural toxins.

[69]  Ž. Ferenčić,et al.  Apoptosis and oxidative stress induced by ochratoxin A in rat kidney , 2003, Archives of Toxicology.

[70]  G. D. Booth,et al.  Effect of ochratoxin and aflatoxin on serum proteins, complement activity, and antibody production to Brucella abortus in guinea pigs. , 1975, Applied microbiology.

[71]  F J Cabañes,et al.  Ochratoxin A production by strains of Aspergillus niger var. niger , 1994, Applied and environmental microbiology.

[72]  R. Dafalla,et al.  Effect on ochratoxin A on Lohmann-type chicks. , 1991, Veterinary and human toxicology.

[73]  S. Macdonald,et al.  Fate of ochratoxin A in the processing of whole wheat grains during milling and bread production , 2003, Food additives and contaminants.

[74]  R. Burns,et al.  Effect of ochratoxin A on immunoglobulins in broiler chicks. , 1984, Research in veterinary science.

[75]  S. Udagawa,et al.  Effect of roasting on ochratoxin A level in green coffee beans inoculated with Aspergillus ochraceus , 1987, Mycopathologia.

[76]  L. Fourie,et al.  Ochratoxin A, a Toxic Metabolite produced by Aspergillus ochraceus Wilh. , 1965, Nature.

[77]  A. Ciegler,et al.  Ochratoxin synthesis byPenicillium species , 1972, Naturwissenschaften.

[78]  J. Dhuley Effect of some Indian herbs on macrophage functions in ochratoxin A treated mice. , 1997, Journal of ethnopharmacology.

[79]  H. Haubeck,et al.  Immunosuppression by ochratoxin A and its prevention by phenylalanine , 1981, Applied and environmental microbiology.

[80]  A. C. Alessi,et al.  The effects of ochratoxin/aluminosilicate interaction on the tissues and humoral immune response of broilers , 2002, Avian pathology : journal of the W.V.P.A.

[81]  E. Creppy,et al.  Inhibition of protein synthesis in mice by ochratoxin A and its prevention by phenylalanine. , 1984, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[82]  S. Salzano,et al.  Ochratoxin A and zearalenone: a comparative study on genotoxic effects and cell death induced in bovine lymphocytes. , 2004, Mutation research.

[83]  A. López de Cerain,et al.  Immunotoxic effects of Ochratoxin A in Wistar rats after oral administration. , 2004, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[84]  M. Pitout The hydrolysis of ochratoxin A by some proteolytic enzymes. , 1969, Biochemical pharmacology.

[85]  K. Failing,et al.  Ochratoxin A induced TNFα release from the isolated and blood- free perfused rat liver , 2000, Mycotoxin Research.

[86]  J. Tuite,et al.  Ochratoxin A and Citrinin Induced Nephrosis in Beagle Dogs II. Pathology , 1977, Veterinary pathology.

[87]  C. Lafarge‐Frayssinet,et al.  Genotoxicity of ochratoxin A in mice: DNA single-strand break evaluation in spleen, liver and kidney. , 1985, Toxicology letters.

[88]  E. Creppy,et al.  Effects of two metabolites of ochratoxin A, (4R)-4-hydroxyochratoxin A and ochratoxin alpha, on immune response in mice , 1983, Infection and immunity.

[89]  S. Silbernagl,et al.  Inhibition of Mitochondria and Extracellular Acidification Enhance Ochratoxin A-induced Apoptosis in Renal Collecting Duct-derived MDCK-C7 Cells , 2004, Cellular Physiology and Biochemistry.

[90]  J. D. May,et al.  Evaluation of immunity of young broiler chickens during simultaneous aflatoxicosis and ochratoxicosis. , 1983, Poultry science.

[91]  R. Röschenthaler,et al.  Inhibition of phenylalanine tRNA synthetase from Bacillus subtilis by ochratoxin A , 1977, FEBS letters.

[92]  M. Stack,et al.  Myelotoxicity and macrophage alteration in mice exposed to ochratoxin A. , 1984, Toxicology and applied pharmacology.

[93]  J. Seegers,et al.  A comparative study of ochratoxin A-induced apoptosis in hamster kidney and HeLa cells. , 1994, Toxicology and applied pharmacology.