Tıpta Yenilikçi Yaklaşımlar Dergisi
Abbreviation: JIAM | ISSN (Online): 2757-7589 | DOI: 10.29329/jiam

Derleme Makalesi | Tıpta Yenilikçi Yaklaşımlar Dergisi 2020, Cil. 1(1) 46-62

Okratoksin A'nın Fiziksel, Kimyasal Özellikleri ve Sinyal Yolakları Üzerine Etkileri

Fevziye Özdemir Şimşek & Nurten Özçelik

ss. 46 - 62   |  DOI: https://doi.org/10.29329/jiam.2020.299.5

Yayın tarihi: Ocak 05, 2021  |   Okunma Sayısı: 30  |  İndirilme Sayısı: 101


Özet

Okratoksin A (OTA), 1965 yılında Aspergillus ochraceus suşlarının ikincil metaboliti olarak keşfedilmiştir. OTA başlıca Penicillium verrucosum, Aspergillus ochraceus ve Aspergillus carbonarius küf mantarı türleri tarafından üretilen bir mikotoksindir. Okratoksin A, renksiz, suda az ancak sulu sodyum bikarbonatlı çözeltilerde iyi çözünen, zayıf organik asit gibi davranan, kristal toz halinde bir bileşiktir. Isıya karşı oldukça dirençlidir. Işık ve havaya dayanıklı olmayıp, nemli ve güneş ışığı gibi koşullara maruz kaldığı zaman bozulabilir.

OTA’nın doğal kontaminasyon dozlarının seçici olarak böbrekleri ve böbrek fonksiyonlarını etkilediği, bunun yanı sıra karaciğer, immün sistem ve beyin hücrelerinin de OTA’nın olası hedefleri olduğu gösterilmiştir. OTA’nın böbrek, karaciğer ve beyin gibi bazı dokularda hasara yol açtığı tespit edildiği görülmektedir. Genel olarak, non-genotoksik karsinojenler sınır etki üreten maddeler olarak düşünülmektedir. Karsinojeninlerin non-genotoxic mekanizmalarından dolayı DNA üzerine direkt kimyasal bir etki içermemektedir, daha çok hedef hücreler üzerine ya da hücre dışı matriks üzerine kanserojen etkiler gösterdikleri düşünülmektedir. OTA serbest radikal oluşturarak lipit peroksidasyonuna neden olur ve toksisitesini ortaya çıkarır. OTA’nın sinyal yolakları üzerine yapılan çalışma sonucunda JNK ve p38 aktivasyonunu teşvik ettiği ortaya koyulmuştur.

Derlemede Okratoksin A’nın fiziksel ve kimyasal özellikleri, sinyal yolakları ve hedef doku-organlarda etkilerinin incelenmesi ve genel literatürün tartışılması amaçlanmıştır.

Anahtar Kelimeler: Okratoksin A; Sinyal Yolakları; Hedef Organ; Böbrek


Bu makaleye nasıl atıf yapılır?

APA 6th edition
Simsek, F.O. & Ozcelik, N. (2020). Okratoksin A'nın Fiziksel, Kimyasal Özellikleri ve Sinyal Yolakları Üzerine Etkileri . Tıpta Yenilikçi Yaklaşımlar Dergisi, 1(1), 46-62. doi: 10.29329/jiam.2020.299.5

Harvard
Simsek, F. and Ozcelik, N. (2020). Okratoksin A'nın Fiziksel, Kimyasal Özellikleri ve Sinyal Yolakları Üzerine Etkileri . Tıpta Yenilikçi Yaklaşımlar Dergisi, 1(1), pp. 46-62.

Chicago 16th edition
Simsek, Fevziye Ozdemir and Nurten Ozcelik (2020). "Okratoksin A'nın Fiziksel, Kimyasal Özellikleri ve Sinyal Yolakları Üzerine Etkileri ". Tıpta Yenilikçi Yaklaşımlar Dergisi 1 (1):46-62. doi:10.29329/jiam.2020.299.5.

Kaynakça
  1. Abdel‐Wahhab, M. A., et al. (2005). "Melatonin counteracts oxidative stress in rats fed an ochratoxin A contaminated diet." Journal of pineal research 38(2): 130-135. [Google Scholar]
  2. Akpinar, H. A., et al. (2019). "Ochratoxin A Sequentially Activates Autophagy and the Ubiquitin-Proteasome System." Toxins 11(11): 615. [Google Scholar]
  3. Al‐Anati, L. and E. Petzinger (2006). "Immunotoxic activity of ochratoxin A." Journal of veterinary pharmacology and therapeutics 29(2): 79-90. [Google Scholar]
  4. Alexander, J., et al. (2006). "Opinion of the scientific panel on contaminants in the food chain on a request from the commission related to ochratoxin A in food." EFSA J 365: 1-56. [Google Scholar]
  5. Ali, A., et al. (2011). "Renoprotective effect of date fruit extract on ochratoxin (A) induced-oxidative stress in distal tubules of rat: A light and electron microscopic study." Kidney Res. J 1: 13-23. [Google Scholar]
  6. Amezqueta, S., et al. (2008). "OTA‐producing fungi isolated from stored cocoa beans." Letters in applied microbiology 47(3): 197-201. [Google Scholar]
  7. Arbillaga, L., et al. (2006). "Oxidative DNA damage induced by ochratoxin A in the HK-2 human kidney cell line: evidence of the relationship with cytotoxicity." Mutagenesis 22(1): 35-42. [Google Scholar]
  8. Assaf, H., et al. (2004). "Ochratoxin A induces apoptosis in human lymphocytes through down regulation of Bcl-xL." Toxicological Sciences 79(2): 335-344. [Google Scholar]
  9. Ba, X. and N. J. Garg (2011). "Signaling mechanism of poly (ADP-ribose) polymerase-1 (PARP-1) in inflammatory diseases." The American journal of pathology 178(3): 946-955. [Google Scholar]
  10. Barut Uyar, B. (2013). "Anne Sütündeki Aflatoksin M1 Ve Okratoksin A Miktarları Ile Annenin Beslenme Durumu Arasındaki Ilişkinin Değerlendirilmesi." [Google Scholar]
  11. Baudrimont, I., et al. (1997). "Prevention of lipid peroxidation induced by ochratoxin A in Vero cells in culture by several agents." Chemico-Biological Interactions 104(1): 29-40. [Google Scholar]
  12. Boesch-Saadatmandi, C., et al. (2008). "Effect of ochratoxin A on redox-regulated transcription factors, antioxidant enzymes and glutathione-S-transferase in cultured kidney tubulus cells." Food and chemical toxicology 46(8): 2665-2671. [Google Scholar]
  13. Boesch‐Saadatmandi, C., et al. (2009). "Ochratoxin A impairs Nrf2‐dependent gene expression in porcine kidney tubulus cells." Journal of animal physiology and animal nutrition 93(5): 547-554. [Google Scholar]
  14. Castegnaro, M., et al. (2006). "Balkan endemic nephropathy: role of ochratoxins A through biomarkers." Molecular nutrition & food research 50(6): 519-529. [Google Scholar]
  15. Cavin, C., et al. (2007). "Reduction in antioxidant defenses may contribute to ochratoxin A toxicity and carcinogenicity." Toxicological Sciences 96(1): 30-39. [Google Scholar]
  16. Corcuera, L.-A., et al. (2015). "Genotoxicity of Aflatoxin B1 and Ochratoxin A after simultaneous application of the in vivo micronucleus and comet assay." Food and Chemical Toxicology 76: 116-124. [Google Scholar]
  17. Dahlmann, A., et al. (1998). "Detailed mapping of ochratoxin A reabsorption along the rat nephron in vivo: the nephrotoxin can be reabsorbed in all nephron segments by different mechanisms." Journal of pharmacology and experimental therapeutics 286(1): 157-162. [Google Scholar]
  18. Dai, Q., et al. (2014). "MicroRNA profiling of rats with ochratoxin A nephrotoxicity." BMC genomics 15(1): 1. [Google Scholar]
  19. Değirmenci, C. (2013). Kırmızı Şarapta Okratoksin A Ve Fumonisin B2 Varlığının İncelenmesi, Fen Bilimleri Enstitüsü. [Google Scholar]
  20. Dhillon, A. S., et al. (2007). "MAP kinase signalling pathways in cancer." Oncogene 26(22): 3279-3290. [Google Scholar]
  21. Eder, S., et al. (2000). "Nephritogenic ochratoxin A interferes with mitochondrial function and pH homeostasis in immortalized human kidney epithelial cells." Pflügers Archiv 440(4): 521-529. [Google Scholar]
  22. Gautier, J.-C., et al. (2001). "Oxidative damage and stress response from ochratoxin A exposure in rats." Free Radical Biology and Medicine 30(10): 1089-1098. [Google Scholar]
  23. Gautier, J.-C., et al. (2001). "Metabolism of ochratoxin A: absence of formation of genotoxic derivatives by human and rat enzymes." Chemical research in toxicology 14(1): 34-45. [Google Scholar]
  24. Gekle, M., et al. (2005). "Ochratoxin A at nanomolar concentrations: a signal modulator in renal cells." Molecular nutrition & food research 49(2): 118-130. [Google Scholar]
  25. Gekle, M., et al. (2000). "Ochratoxin A induces JNK activation and apoptosis in MDCK-C7 cells at nanomolar concentrations." Journal of pharmacology and experimental therapeutics 293(3): 837-844. [Google Scholar]
  26. Giray, B., et al. (2009). "Çocuklarda serum okratoksin A düzeyleri Orijinal Araştırma." Türk Pediatri Arşivi 44(4). [Google Scholar]
  27. Grosse, Y., et al. (1997). "Retinol, ascorbic acid and α-tocopherol prevent DNA adduct formation in mice treated with the mycotoxins ochratoxin A and zearalenone." Cancer letters 114(1-2): 225-229. [Google Scholar]
  28. Hanahan, D. and R. A. Weinberg (2000). "The hallmarks of cancer." cell 100(1): 57-70. [Google Scholar]
  29. Hoehler, D. and R. R. Marquardt (1996). "Influence of vitamins E and C on the toxic effects of ochratoxin A and T-2 toxin in chicks." Poultry science 75(12): 1508-1515. [Google Scholar]
  30. Huang, F. J. and W. H. Chan (2014). "Effects of ochratoxin a on mouse oocyte maturation and fertilization, and apoptosis during fetal development." Environmental toxicology. [Google Scholar]
  31. IARC, W. (1993). "Some naturally occurring substances: food items and constituents, heterocyclic aromatic amines and mycotoxins." IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans 56. [Google Scholar]
  32. Jennings, P., et al. (2012). "Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model." Archives of toxicology 86(4): 571-589. [Google Scholar]
  33. Jo, S.-K., et al. (2005). "MEK inhibitor, U0126, attenuates cisplatin-induced renal injury by decreasing inflammation and apoptosis." Kidney international 67(2): 458-466. [Google Scholar]
  34. Kamp, H. G., et al. (2005). "Ochratoxin A induces oxidative DNA damage in liver and kidney after oral dosing to rats." Molecular nutrition & food research 49(12): 1160-1167. [Google Scholar]
  35. Klarić, M. Š., et al. (2007). "Lipid peroxidation and glutathione levels in porcine kidney PK15 cells after individual and combined treatment with fumonisin B1, beauvericin and ochratoxin A." Basic & clinical pharmacology & toxicology 100(3): 157-164. [Google Scholar]
  36. Krska, R. and A. Molinelli (2007). "Mycotoxin analysis: state-of-the-art and future trends." Analytical and bioanalytical chemistry 387(1): 145-148. [Google Scholar]
  37. Kumar, R., et al. (2013). "Ochratoxin A-induced cell proliferation and tumor promotion in mouse skin by activating the expression of cyclin-D1 and cyclooxygenase-2 through nuclear factor-kappa B and activator protein-1." Carcinogenesis 34(3): 647-657. [Google Scholar]
  38. Lakhani, S. A., et al. (2006). "Caspases 3 and 7: key mediators of mitochondrial events of apoptosis." Science 311(5762): 847-851. [Google Scholar]
  39. Lee, J.-Y., et al. (2019). "Ochratoxin A mediates cytotoxicity through the MAPK signaling pathway and alters intracellular homeostasis in bovine mammary epithelial cells." Environmental Pollution 246: 366-373. [Google Scholar]
  40. Lioi, M., et al. (2004). "Ochratoxin A and zearalenone: a comparative study on genotoxic effects and cell death induced in bovine lymphocytes." Mutation Research/Genetic Toxicology and Environmental Mutagenesis 557(1): 19-27. [Google Scholar]
  41. Lobeau, M., et al. (2005). "Development of a new clean-up tandem assay column for the detection of ochratoxin A in roasted coffee." Analytica chimica acta 538(1-2): 57-61. [Google Scholar]
  42. Marin-Kuan, M., et al. (2006). "A toxicogenomics approach to identify new plausible epigenetic mechanisms of ochratoxin a carcinogenicity in rat." Toxicological Sciences 89(1): 120-134. [Google Scholar]
  43. Meeting, J. F. W. E. C. o. F. A. and W. H. Organization (2007). Evaluation of certain food additives and contaminants: sixty-eighth report of the Joint FAO/WHO Expert Committee on Food Additives, World Health Organization. [Google Scholar]
  44. Özcan, Z., et al. (2014). "Ochratoxin A activates opposing c-MET/PI3K/Akt and MAPK/ERK 1-2 pathways in human proximal tubule HK-2 cells." Archives of toxicology: 1-15. [Google Scholar]
  45. Özçelik, N., et al. (2001). "Ochratoxin A in human serum samples collected in Isparta-Turkey from healthy individuals and individuals suffering from different urinary disorders." Toxicology letters 121(1): 9-13. [Google Scholar]
  46. Palma, N., et al. (2007). "Ochratoxin A-induced mutagenesis in mammalian cells is consistent with the production of oxidative stress." Chemical research in toxicology 20(7): 1031-1037. [Google Scholar]
  47. Petrik, J., et al. (2003). "Apoptosis and oxidative stress induced by ochratoxin A in rat kidney." Archives of toxicology 77(12): 685-693. [Google Scholar]
  48. Pfohl‐Leszkowicz, A. and R. A. Manderville (2007). "Ochratoxin A: An overview on toxicity and carcinogenicity in animals and humans." Molecular nutrition & food research 51(1): 61-99. [Google Scholar]
  49. Proskuryakov, S. Y., et al. (2003). "Necrosis: a specific form of programmed cell death?" Experimental cell research 283(1): 1-16. [Google Scholar]
  50. Qi, X., et al. (2014). "Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses." Toxicology and applied pharmacology 280(3): 543-549. [Google Scholar]
  51. Ramyaa, P. and V. V. Padma (2013). "Ochratoxin-induced toxicity, oxidative stress and apoptosis ameliorated by quercetin–Modulation by Nrf2." Food and Chemical Toxicology 62: 205-216. [Google Scholar]
  52. Ramyaa, P. and V. V. Padma (2014). "Quercetin modulates OTA-induced oxidative stress and redox signalling in HepG2 cells—up regulation of Nrf2 expression and down regulation of NF-κB and COX-2." Biochimica et Biophysica Acta (BBA)-General Subjects 1840(1): 681-692. [Google Scholar]
  53. Ringot, D., et al. (2006). "Toxicokinetics and toxicodynamics of ochratoxin A, an update." Chemico-Biological Interactions 159(1): 18-46. [Google Scholar]
  54. Roth, A., et al. (1993). "Kinetic properties of pure overproduced Bacillus subtilis phenylalanyl-tRNA synthetase do not favour its in vivo inhibition by ochratoxin A." FEBS letters 326(1): 87-91. [Google Scholar]
  55. Sabuncuoğlu, S. A., et al. (2008). "Mikotoksinler: toksik etkileri, degredasyonları, oluşumlarının önlenmesi ve zararlı etkilerinin azaltılması." Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi(1): 63-92. [Google Scholar]
  56. Sauvant, C., et al. (2005). "The nephrotoxin ochratoxin A induces key parameters of chronic interstitial nephropathy in renal proximal tubular cells." Cellular physiology and biochemistry 15(1-4): 125-134. [Google Scholar]
  57. Schramek, H., et al. (1997). "Ochratoxin A-induced stimulation of extracellular signal-regulated kinases 1/2 is associated with Madin-Darby canine kidney-C7 cell dedifferentiation." Journal of pharmacology and experimental therapeutics 283(3): 1460-1468. [Google Scholar]
  58. Schwerdt, G., et al. (1996). "Accumulation of ochratoxin A in rat kidney in vivo and in cultivated renal epithelial cells in vitro." Toxicology 114(3): 177-185. [Google Scholar]
  59. Schwerdt, G., et al. (1999). "The nephrotoxin ochratoxin A induces apoptosis in cultured human proximal tubule cells." Cell biology and toxicology 15(6): 405-415. [Google Scholar]
  60. Sedefoğlu, C. (2013). Antep Fıstıklarında Okratoksin A Ve Aflatoksin Varlığının İncelenmesi, Fen Bilimleri Enstitüsü. [Google Scholar]
  61. Sinha, K., et al. (2013). "Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis." Archives of toxicology 87(7): 1157-1180. [Google Scholar]
  62. Soyöz, M. and N. Özçelik (2002). "Okratoksin A'nın Toksik Etkileri Ve Eliminasyonu." Turkiye Klinikleri Journal of Medical Sciences 22(4): 421-427. [Google Scholar]
  63. Stoev, S. D., et al. (2012). "Experimental mycotoxic nephropathy in pigs provoked by a mouldy diet containing ochratoxin A and fumonisin B1." Experimental and Toxicologic Pathology 64(7-8): 733-741. [Google Scholar]
  64. Subramaniam, S., et al. (2004). "ERK activation promotes neuronal degeneration predominantly through plasma membrane damage and independently of caspase-3." The Journal of cell biology 165(3): 357-369. [Google Scholar]
  65. Tewari, M., et al. (1995). "Yama/CPP32β, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly (ADP-ribose) polymerase." cell 81(5): 801-809. [Google Scholar]
  66. Tian, W., et al. (2000). "MAPK signaling and the kidney." American Journal of Physiology-Renal Physiology 279(4): F593-F604. [Google Scholar]
  67. Trachootham, D., et al. (2008). "Redox regulation of cell survival." Antioxidants & redox signaling 10(8): 1343-1374. [Google Scholar]
  68. Van der Merwe, K., et al. (1965). "The constitution of ochratoxins A, B, and C, metabolites of Aspergillus ochraceus wilh." Journal of the Chemical Society (Resumed): 7083-7088. [Google Scholar]
  69. Vettorazzi, A., et al. (2013). "A review on ochratoxin A transcriptomic studies." Food and Chemical Toxicology 59: 766-783. [Google Scholar]
  70. Wang, X., et al. (2000). "Requirement for ERK activation in cisplatin-induced apoptosis." Journal of Biological Chemistry 275(50): 39435-39443. [Google Scholar]
  71. Wangikar, P. B., et al. (2007). "Teratogenic Effects of Ochratoxin A and Aflatoxin B 1 Alone and in Combination on Post-Implantation Rat Embryos in Culture." Journal of the Turkish-German Gynecological Association 8(4). [Google Scholar]
  72. Weston, C. R. and R. J. Davis (2002). "The JNK signal transduction pathway." Current opinion in genetics & development 12(1): 14-21. [Google Scholar]
  73. Wilmes, A., et al. (2011). "Identification and dissection of the Nrf2 mediated oxidative stress pathway in human renal proximal tubule toxicity." Toxicology in Vitro 25(3): 613-622. [Google Scholar]
  74. Yamamoto, T., et al. (2006). "Continuous ERK activation downregulates antiproliferative genes throughout G1 phase to allow cell-cycle progression." Current Biology 16(12): 1171-1182. [Google Scholar]
  75. Ziegler, K. (2000). "Ochratoxin A from a toxicological perspective." J. Vet. Pharmacol. Ther 23: 91-98. [Google Scholar]