Ochratoxin A
| Ochratoxin A | |
|---|---|
 |
|
|
N-{[(3R)-5-chloro-8-hydroxy-3-methyl-1-oxo-3,4-dihydro-1H-isochromen-7-yl]carbonyl}-L-phenylalanine |
|
|
Other names
(R)-N- [(5-Chloro- 3,4-dihydro- 8-hydroxy- 3-methyl- 1-oxo- 1H-2-benzopyran-7-yl) -carbonyl]- L- phenylalanine |
|
| Identifiers | |
| CAS number | 303-47-9  |
| PubChem | 442530 |
| ChemSpider | 390954 |
| KEGG | C09955 |
| ChEBI | CHEBI:7719 |
| ChEMBL | CHEMBL589366 |
| Jmol-3D images | Image 1 |
|
|
|
|
| Properties | |
| Molecular formula | C20H18ClNO6 |
| Molar mass | 403.81 g mol−1 |
 (verify) (what is:  / ?)Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) |
|
| Infobox references | |
Ochratoxin A, a toxin produced by Aspergillus ochraceus, Aspergillus carbonarius and Penicillium verrucosum, is one of the most abundant food-contaminating mycotoxins .[1]. . It is also a frequent contaminant of water-damaged houses [2] and of heating ducts [3]. Human exposure can occur through consumption of contaminated food products,[4] particularly contaminated grain and pork products, as well as coffee[5], wine grapes [6] and dried grapes. The toxin has been found in the tissues and organs of animals, including human blood and breast milk.[7] Ochratoxin A, like most toxic substances, has large species- and sex-specific toxicological differences.[5]
Contents |
[edit] Impact on human and animal health
[edit] Carcinogenicity
Ochratoxin A is potentially carcinogenic to humans (Group 2B). Ochratoxin A has been shown to be weakly mutagenic, possibly by induction of oxidative DNA damage.[8]
There is sufficient evidence in experimental animals for the carcinogenicity of ochratoxin A. Ochratoxin A was tested for carcinogenicity by oral administration in mice and rats. It increased the incidence of hepato-cellular carcinomas in mice of each sex and produced renal-cell adenomas and carcinomas in male mice and in rats of each sex.
[edit] Neurotoxicity
Ochratoxin A has a strong affinity for the brain, especially the cerebellum (Purkinje cells), ventral mesencephalon and hippocampal structures[9]. The affinity for the hippocampus could be relevant to the pathogenesis of Alzheimer's disease, and subchronic administration to rodents induces hippocampal neurodegeneration. Ochratoxin causes acute depletion of striatal dopamine [10], which constitutes the bed of Parkinson's disease. Teams from Zheijiang Univ. and Kiel Univ. hold that Ochratoxin may contribute to Alzheimer's and to Parkinson's diseases[11] The developing brain is very susceptible to ochratoxin, hence the need for caution during pregnancy[12]. .
[edit] Immuno suppression and immunotoxicity
Ochratoxin A can cause immunosuppression and immunotoxicity in animals.[1] The toxin's immunosuppressant activity in animals may include depressed antibody responses, reduced size of immune organs (such as the thymus, spleen, and lymph nodes), changes in immune cell number and function, and altered cytokine production.[1] Immunotoxicity probably results from cell death following apoptosis and necrosis, in combination with slow replacement of affected immune cells due to inhibition of protein synthesis.[1]
[edit] Potential link to Balkan endemic nephropathy
A number of descriptive studies have suggested a correlation between exposure to ochratoxin A and Balkan endemic nephropathy, and have found a correlation between the geographical distribution of Balkan endemic nephropathy and a high incidence of, and mortality from, urothelial urinary tract tumours.[13] However, there is currently insufficient information to conclusively link ochratoxin A to Balkan endemic nephropathy.[14] The toxin may require synergistic interactions with predisposing genotypes or other environmental toxicants to induce Balkan endemic nephropathy.[15]
[edit] Food animal industry impact
Ochratoxin-contaminated feed has its major economic impact on the poultry industry. Chickens, turkeys and ducklings are susceptible to this toxin. Clinical signs of avian ochratoxicosis generally involve reduction in weight gains, poor feed conversion, reduced egg production, and poor egg shell quality .[16] . Economic losses occur also in swine farms, linked to nephropathy and costs for the disposal of carcasses.
Toxicity does not seem to constitute a problem in cattle, as the rumen harbors protozoa that hydrolyze OTA [17].However contamination of milk is a possibility.
[edit] Dietary guidelines
The "Tolerable daily intake" (TDI) of Ochratoxin is 5 ng/kg. In the US mean body weight for men is 86 Kg, and for women 74 Kg. Hence the the TDI for men is 430 ng and the TDI for women 370 ng. In the joined table "weight in Kg" is the weight eaten per day of each of the listed foodstuffs. Diet 1, with small quantities of ginger, nutmeg and paprika, a good serving of dry raisins, a reasonable amount of coffee, cereals, wine, pulses, and salami, amounts to a safe diet(as for Ochratoxin at least), with 286 ng per day. However It would be easy to go into excessive levels (Diet 1+), just by eating 200 g of pig kidney, and chewing 200 g of peanuts, which would lead to a total of nearly 462 ng of ochratoxin. This shows how delicate a safe diet can be.
[edit] See also
[edit] References
- ^ a b c d Al-Anati L, Petzinger E (2006). "Immunotoxic activity of ochratoxin A". J. Vet. Pharmacol. Ther. 29 (2): 79–90. doi:10.1111/j.1365-2885.2006.00718.x. PMID 16515661.
- ^ Polizzi V., Delmulle B., Adams N., Moretti A., Susca A., Picco AM., Rosseel Y., Kindt Ruben't, Bocxlaer JV., De Kimpe N., Van Peteghem C., De Saeger S. "Fungi, mycotoxins and volatile organic compounds in mouldy interiors from water-damaged buildings". Journal of Environmental Monitoring 11 : 1849-1858; 2009
- ^ Richard JL, Plattner RD, May J, Liska SL (1999.). "The occurrence of ochratoxin A in dust collected from a problem household". Mycopathologia 146 (2): 99-103.
- ^ Pfohl-Leszkowicz A, Manderville RA (2007). "Ochratoxin A: An overview on toxicity and carcinogenicity in animals and humans". Mol Nutr Food Res 51 (1): 61–99. doi:10.1002/mnfr.200600137. PMID 17195275.
- ^ a b O'Brien E, Dietrich DR (2005). "Ochratoxin A: the continuing enigma". Crit. Rev. Toxicol. 35 (1): 33–60. doi:10.1080/10408440590905948. PMID 15742902.
- ^ Blesa J, Soriano JM, Moltó JC, Mañes J (2006). "Factors affecting the presence of ochratoxin A in wines". Critical reviews in food science and nutrition 46 (6): 473–8. doi:10.1080/10408390500215803. PMID 16864140.
- ^ Clark HA, Snedeker SM (2006). "Ochratoxin A: its cancer risk and potential for exposure". Journal of toxicology and environmental health. Part B, Critical reviews 9 (3): 265–96. doi:10.1080/15287390500195570. PMID 16621780.
- ^ Palma N, Cinelli S, Sapora O, Wilson SH, Dogliotti E (2007). "Ochratoxin A-Induced Mutagenesis in Mammalian Cells Is Consistent with the Production of Oxidative Stress". Chemical Research in Toxicology 20 (7): 1031–1037. doi:10.1021/tx700027j. PMC 2367102. PMID 17567156. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2367102.
- ^ Belmadani A. Steyn PS. Tramu G. Betbeder AM. Baudrimont I. Creppy EE. (1999). "Selective toxicity of ochratoxin A in primary cultures from different brain regions". Arch Toxicol 73 (2): 108–114.
- ^ Sava V. Reunova O. Velasquez A. Harbison A. (2006.). "Acute neurotoxic effects of the fungal metabolite ochratoxin A". Neurotoxicology 27 (1): 82-92.
- ^ Xiangnan Zhang , Christine Boesch-Saadatmandi , Yijia Lou , Siegfried Wolffram , Patricia Huebbe , Gerald Rimbach (2009). "Ochratoxin A induces apoptosis in neuronal cells". Genes Nutr 4: 41–48.
- ^ Kunio Doi, Koji Uetsuka (2011). "Ochratoxin A induces apoptosis in neuronal cells". International Journal of Molecular Sciences 12: 5213–5327.
- ^ Castegnaro M, Canadas D, Vrabcheva T, Petkova-Bocharova T, Chernozemsky IN, Pfohl-Leszkowicz A (2006). "Balkan endemic nephropathy: role of ochratoxins A through biomarkers". Mol Nutr Food Res 50 (6): 519–29. doi:10.1002/mnfr.200500182. PMID 16715544.
- ^ Long DT, Voice TC (2007). "Role of exposure analysis in solving the mystery of Balkan endemic nephropathy". Croat. Med. J. 48 (3): 300–11. PMC 2080532. PMID 17589972. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2080532.
- ^ Abouzied MM, Horvath AD, Podlesny PM, et al. (2002). "Ochratoxin A concentrations in food and feed from a region with Balkan Endemic Nephropathy". Food additives and contaminants 19 (8): 755–64. doi:10.1080/02652030210145036. PMID 12227939.
- ^ J. Niemiec, W. Borzemska , The effect of Ochratoxin A on egg quality development of embryos and the level of toxin in egg and tissue of hens and chicks, Journal of Animal and Feed Sciences , 3 , (4) , 309-316, 1994
- ^ Battacone G. Nudda A. Pulina G. (2010). "Effects of Ochratoxin A on Livestock Production". Toxins 2: 1796–1824.
