Turkiye Klinikleri Journal of Veterinary Sciences

.: REVIEW
Bir Mikotoksin Türü Olan Hormonal Etkili Zearalenonun İncelenmesi: Sistematik Derleme
Investigation of Zearalenone, a Type of Mycotoxin with Hormonal Effects: Systematic Review
Çağla ÇELEBİa , Hasan SUSARa , İzzet KARAHANa
aBalıkesir Üniversitesi Veteriner Fakültesi, Farmakoloji ve Toksikoloji AD, Balıkesir, Türkiye
Turkiye Klinikleri J Vet Sci. 2024;15(2):61-71
doi: 10.5336/vetsci.2024-101977
Article Language: TR
Full Text
ÖZET
Mikotoksinler gıdalarda yaygın olarak bulunan, canlı sağlığı üzerine olumsuz etkilerin yanı sıra büyük ekonomik kayıplara sebep olan ikincil metabolitlerdir. Sıklıkla karşılaşılması özellikle halk ve hayvan sağlığı endişesi doğurmaktadır. Bu nedenle birçok ülkede bulunmaları gereken üst limit değerleri belirlenmiştir. Moleküler yapıları ve toksisiteleri farklı olan birçok mikotoksin vardır. Bu mikotoksinlerden bir tanesi olan zearalenon; Fusarium ailesine bağlı farklı mantar türlerinden sentezlenmektedir. Başlıca mısır, buğday, arpa, yulaf, sorgum, çavdar, pirinç gibi ürünlerde kontaminasyon oluşturmaktadır. En önemli özelliği ise hormonal etkili bir mikotoksin olmasıdır. Özellikle17-β estradiol ile yarışarak östrojen reseptörüne bağlanır ve bunun sonucunda hiperöstrojenik semptomlar oluşturur. Bu nedenle östrojen etkili mikotoksin olarak da isimlendirilmektedir. Hayvan türleri arasında zearalenona karşı duyarlılık farklılık göstermektedir. Lipofilik özelliği ile maruziyet sonrası hızlı emilim göstermesi toksisite tablosunun da hızlı şekillenmesine yol açmaktadır. Ayrıca kendisi haricînde 5 farklı metaboliti mevcuttur. Metabolitlerinin de toksik özellik göstermesi oldukça farklı toksisite tablolarının şekillenmesine neden olmaktadır. Özellikle son yıllarda sucul ekosistemin küfler ve toksinlerle kontamine olması bulaşma konusunda büyük riske sebep olmuştur. İnsan ve hayvan tüketimine sunulan ürünlerde mikotoksin varlığının araştırılması, limit değerlere yakınlık gibi birçok farklı konu günümüzde hâlâ araştırılmaktadır. Mikotoksinler arasında en düşük araştırma payı diğerlerinin aksine zearalenona aittir. Hormon etkili olmasının yanı sıra bu amaçla farklı alanlarda (yasaklı olmasına rağmen) kullanımının olması, zearalenon hakkında daha büyük çaplı araştırmalar yapılması ihtiyacını artırmıştır. Mikotoksinlere ve özellikle de zearalenona gerekli önemin verilmesine destek olmak amacıyla bu derleme hazırlanmıştır.

Anahtar Kelimeler: Mikotoksin; zearalenon; hormon
ABSTRACT
Mycotoxins are secondary metabolites that are widely found in foods and cause great economic losses as well as negative effects on living health. Their frequent occurrence raises public and animal health concerns. For this reason, upper limit values have been set in many countries. There are many mycotoxins with different molecular structures and toxicities. Zearalenone, one of these mycotoxins, is synthesized by different fungal species of the Fusarium family. It mainly contaminates crops such as corn, wheat, barley, oats, sorghum, rye and rice. Its most important feature is that it is a hormonal mycotoxin. In particular, it competes with 17-β estradiol and binds to the estrogen receptor, resulting in hyperestrogenic symptoms. For this reason, it is also called estrogen-acting mycotoxin. Sensitivity to zearalenone varies among animal species. Its lipophilic characteristic and rapid absorption after exposure lead to rapid formation of toxicity picture. It also has 5 different metabolites besides itself. The fact that its metabolites also show toxic properties leads to the formation of quite different toxicity tables. Especially in recent years, contamination of the aquatic ecosystem with molds and toxins has caused a great risk of contamination. Many different issues such as the presence of mycotoxins in products offered for human and animal consumption and proximity to limit values are still being investigated today. Unlike others, zearalenone has the lowest research share among mycotoxins. The fact that zearalenone is used in different fields (although banned) for this purpose, as well as being hormone effective, has increased the need for larger-scale research on zearalenone. This review has been prepared to support the necessary attention to mycotoxins and zearalenone in particular.

Keywords: Mycotoxin; zearalenone; hormone
REFERENCES:
  1. McDonald P, Edwards RA, Greenhalgh JFD, Morgan CA, Sinclair LA, Wilkinson RG. Animal Nutrition. 8th ed. Harlow, England: Gosport, Ashford Colour Press Ltd; 2022.
  2. Singh S, Kumar V, Dhanjal DS, Dhaka V, Sonali, Singh J. Mycotoxin metabolites of fungi. In: Singh J, Gehlot P, eds. New and Future Developments in Microbial Biotechnology and Bioengineering. 1st ed. Amsterdam, Netherlands: Elsevier; 2021. p.253-65. [Crossref] 
  3. Rogowska A, Pomastowski P, Sagandykova G, Buszewski B. Zearalenone and its metabolites: Effect on human health, metabolism and neutralisation methods. Toxicon. 2019;162:46-56. [Crossref]  [PubMed] 
  4. Stępień L. The use of Fusarium secondary metabolite biosynthetic genes in chemotypic and phylogenetic studies. Crit Rev Microbiol. 2014;40(2):176-85. [Crossref]  [PubMed] 
  5. Hussein HS, Brasel JM. Toxicity, metabolism, and impact of mycotoxins on humans and animals. Toxicology. 2001;167(2):101-34. [Crossref]  [PubMed] 
  6. Manstretta V, Rossi V. Effects of temperature and moisture on development of fusarium graminearum perithecia in maize stalk residues. Appl Environ Microbiol. 2015;82(1):184-91. [Crossref]  [PubMed]  [PMC] 
  7. Llorens A, Mateo R, Hinojo MJ, Logrieco A, Jimenez M. Influence of the interactions among ecological variables in the characterization of zearalenone producing isolates of Fusarium spp. Syst Appl Microbiol. 2004;27(2):253-60. [Crossref]  [PubMed] 
  8. Hope R, Aldred D, Magan N. Comparison of environmental profiles for growth and deoxynivalenol production by Fusarium culmorum and F. graminearum on wheat grain. Lett Appl Microbiol. 2005;40(4):295-300. [Crossref]  [PubMed] 
  9. Váry Z, Mullins E, McElwain JC, Doohan FM. The severity of wheat diseases increases when plants and pathogens are acclimatized to elevated carbon dioxide. Glob Chang Biol. 2015;21(7):2661-9. [Crossref]  [PubMed] 
  10. Toptaş Ö, Erköse-Genç GE. Yaygın mikotoksinler: aflatoksinler, okratoksin a, fumonisinler, deoksinivalenol ve zearalenon [Common mycotoxins: aflatoxins, ochratoxin a, fumonisins, deoxynivalenol, zearalenone]. Ankara Sağlık Bilimleri Dergisi. 2023;12(1):87-98. [Crossref] 
  11. Borreani G, Tabacco E, Antoniazzi S, Cavallarin L. Zearalenone contamination in farm maize silage. Italian Journal of Animal Science. 2005;4(2):162-5. [Crossref] 
  12. Boudra H, Morgavi DP. Reduction in fusarium toxin levels in corn silage with low dry matter and storage time. J Agric Food Chem. 2008;56(12):4523-8. [Crossref]  [PubMed] 
  13. Jensen T, De Boevre M, De Saeger S, Preußke N, Sönnichsen FD, Kramer E, et al. Effect of ensiling duration on the fate of deoxynivalenol, zearalenone and their derivatives in maize silage. Mycotoxin Res. 2020;36(2):127-36. [Crossref]  [PubMed] 
  14. González Pereyra ML, Sulyok M, Baralla V, Dalcero AM, Krska R, Chulze S, et al. Evaluation of zearalenone, α-zearalenol, β-zearalenol, zearalenone 4-sulfate and β-zearalenol 4-glucoside levels during the ensiling process. World Mycotoxin J. 2014;7(3):291-5. [Crossref] 
  15. Keller LAM, Gonzalez-Pereyra ML, Keller KM, Alonso VA, Oliveira AA, Almeida TX, et al. Fungal and mycotoxins contamination in corn silage:monitoring risk before and after fermentation. J Stored Prod Res. 2013;52:42-7. [Crossref] 
  16. Liu C, Van der Fels-Klerx HJ. Quantitative modeling of climate change impacts on mycotoxins in cereals: a review. Toxins (Basel). 2021;13(4):276. [Crossref]  [PubMed]  [PMC] 
  17. Annunziata L, Schirone M, Visciano P, Campana G, De Massis MR., Migliorati G. Determination of aflatoxins, deoxynivalenol, ochratoxin A and zearalenone in organic wheat flour under different storage conditions. International Journal of Food Science and Technology. 2021;56(8):4139-48. [Crossref] 
  18. Yazar S, Omurtag GZ. Fumonisins, trichothecenes and zearalenone in cereals. Int J Mol Sci. 2008;9(11):2062-90. [Crossref]  [PubMed]  [PMC] 
  19. Kayişoğlu Ç, Türksoy S. Ozon uygulamasının tahıl ve ürünleri üzerindeki etkileri [The effect of ozone treatment on cereals and products]. Gıda. 2023;48(2):285-304. [Crossref] 
  20. Sekiyama BL, Ribeiro AB, Machinski PA, Junior MM. Aflatoxins, ochratoxin a and zearalenone in maize-based food products. Brazilian Journal of Microbiology. 2005;36(3):289-94. [Crossref] 
  21. Malekinejad H, Maas-Bakker R, Fink-Gremmels J. Species differences in the hepatic biotransformation of zearalenone. Vet J. 2006;172(1):96-102. [Crossref]  [PubMed] 
  22. Kwasniewska K, Gadza R, Kopciuch RG, Cendrowski K. Analytical procedure for the determination of zearalenone in environmental and biological samples. Critical Reviews in Analytical Chemistry. 2015;45(2):119-30. [Crossref]  [PubMed] 
  23. Stein RA, Bulboacӑ AE. Mycotoxins. In: Dodd CER, Aldsworth T, Stein RA, Cliver DO, Riemann HP, eds. Foodborne Diseases. 3rd ed. London, United Kingdom: Academic Press; 2017. p.407-46. [Crossref]  [PMC] 
  24. Kriszt R, Krifaton C, Szoboszlay S, Cserháti M, Kriszt B, Kukolya J, et al. A new zearalenone biodegradation strategy using non-pathogenic Rhodococcus pyridinivorans K408 strain. PLoS One. 2012;7(9):e43608. [Crossref]  [PubMed]  [PMC] 
  25. Schollenberger M, Müller HM, Rüfle M, Suchy S, Planck S, Drochner W. Survey of Fusarium toxins in foodstuffs of plant origin marketed in Germany. Int J Food Microbiol. 2005;97(3):317-26. [Crossref]  [PubMed] 
  26. Wang Y, Chai T, Lu G, Quan C, Duan H, Yao M, et al. Simultaneous detection of airborne aflatoxin, ochratoxin and zearalenone in a poultry house by immunoaffinity clean-up and high-performance liquid chromatography. Environ Res. 2008;107(2):139-44. [Crossref]  [PubMed] 
  27. Kuiper-Goodman T, Scott PM, Watanabe H. Risk assessment of the mycotoxin zearalenone. Regul Toxicol Pharmacol. 1987;7(3):253-306. [Crossref]  [PubMed] 
  28. Devreese M, Antonissen G, Broekaert N, De Baere S, Vanhaecke L, De Backer P, et al. Comparative toxicokinetics, absolute oral bioavailability, and biotransformation of zearalenone in different poultry species. J Agric Food Chem. 2015;63(20):5092-8. [Crossref]  [PubMed] 
  29. Liang Z, Ren Z, Gao S, Chen Y, Yang Y, Yang D, et al. Individual and combined effects of deoxynivalenol and zearalenone on mouse kidney. Environ Toxicol Pharmacol. 2015;40(3):686-91. [Crossref]  [PubMed] 
  30. Dänicke S, Winkler J. Invited review: Diagnosis of zearalenone (ZEN) exposure of farm animals and transfer of its residues into edible tissues (carry over). Food Chem Toxicol. 2015;84:225-49. [Crossref]  [PubMed] 
  31. Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, et al. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology. 1998;139(10):4252-63. [Crossref]  [PubMed] 
  32. Zinedine A, Soriano JM, Moltó JC, Mañes J. Review on the toxicity, occurrence, metabolism, detoxification, regulations and intake of zearalenone: an oestrogenic mycotoxin. Food Chem Toxicol. 2007;45(1):1-18. [Crossref]  [PubMed] 
  33. Kar P. Fumonisinlerin oluşum mekanizması ve metabolizmada subakut, kronik etkisinin sonuçları [Formation mechanism of fumonisins and results of subacute and chronic effects on metabolism]. Recep Tayyip Erdoğan Üniversitesi Fen ve Mühendislik Bilimleri Dergisi. 2022;3(2):115-24. [Crossref] 
  34. Tatay E, Espín S, García-Fernández AJ, Ruiz MJ. Oxidative damage and disturbance of antioxidant capacity by zearalenone and its metabolites in human cells. Toxicol In Vitro. 2017;45(Pt 3):334-9. [Crossref]  [PubMed] 
  35. Tangni EK, Pussemier L, Van Hove F. Mycotoxin contaminating maize and grass silages for dairy cattle feeding: current state and challenges. J Anim Sci Adv. 2013;3(10):492-511. [Link] 
  36. Molina-Molina JM, Real M, Jimenez-Diaz I, Belhassen H, Hedhili A, Torné P, et al. Assessment of estrogenic and anti-androgenic activities of the mycotoxin zearalenone and its metabolites using in vitro receptor-specific bioassays. Food Chem Toxicol. 2014;74:233-9. [Crossref]  [PubMed] 
  37. Wu F. Foodborne mycotoxins. In: Morris JG, Vugia DJ, eds. Foodborne Infections and Intoxications. 5th ed. Amsterdam: Academic Press; 2021. p.439-54. [Crossref] 
  38. Gromadzka K, Waśkiewicz A, Goliński P, Swietlik J. Occurrence of estrogenic mycotoxin - Zearalenone in aqueous environmental samples with various NOM content. Water Res. 2009;43(4):1051-9. [Crossref]  [PubMed] 
  39. Kowalska K, Habrowska-Górczyńska DE, Piastowska-Ciesielska AW. Zearalenone as an endocrine disruptor in humans. Environ Toxicol Pharmacol. 2016;48:141-9. [Crossref]  [PubMed] 
  40. Oruç HH. Süt ve süt ürünlerinde aflatoksin M1 (AFM1) ve Türkiye'deki durumu [Aflatoxin M1 (AFM1) in milk and dairy products and its status in Turkey]. Uludağ Üniversitesi Veteriner Fakültesi Dergisi. 2003:1-2-3:121-5. [Link] 
  41. Polat C, Koç F. Özdüven ML. Mısır silajında laktik asit bakteri ve laktik asit bakteri+enzim karışımı inokulantların fermantasyon ve toklularda ham besin maddelerinin sindirilme dereceleri üzerine etkileri [Effects of lactic acid bacteria and lactic acid bacteria + enzyme mixture inoculants on fermentation and digestibility of raw nutrients in corn silage]. Tekirdağ Ziraat Fakültesi Dergisi. 2012;2(1):13-22. [Link] 
  42. Szabó A, Szabó-Fodor J, Fébel H, Mézes M, Balogh K, Bázár G, et al. Individual and Combined Effects of Fumonisin B₁, Deoxynivalenol and Zearalenone on the Hepatic and Renal Membrane Lipid Integrity of Rats. Toxins (Basel). 2017;10(1):4. [Crossref]  [PubMed]  [PMC] 
  43. Ropejko K, Twarużek M. Zearalenone and its metabolites-general overview, occurrence, and toxicity. Toxins (Basel). 2021;13(1):35. [Crossref]  [PubMed]  [PMC] 
  44. Aydın M, Rencüzoğulları E. Mikotoksinlerin genotoksik ve mutajenik etkileri: derleme [Genotoxic and mutagenic effects of mycotoxins: a review]. Commagene Journal of Biology. 2019;3(2):132-61. [Link] 
  45. Flannigan B. Mycotoxins. In: D'Mello JPF, Duffus CM, Duffus JH, eds. Toxic Substances in Crop Plants. 1st ed. Cambridge: The Royal Society of Chemistry; 1991. p.226-57. [Crossref] 
  46. Mostrom M. Trichothecenes and zearalenone. Reproductive and Developmental Toxicology. 2011;54:739-51. [Crossref] 
  47. Gbore FA, Egbunike GN. Testicular and epididymal sperm reserves and sperm production of pubertal boars fed dietary fumonisin B(1). Anim Reprod Sci. 2008;105(3-4):392-7. [Crossref]  [PubMed] 
  48. Xu H, Wang L, Sun J, Wang L, Guo H, Ye Y, et al. Microbial detoxification of mycotoxins in food and feed. Crit Rev Food Sci Nutr. 2022;62(18):4951-69. [Crossref]  [PubMed] 
  49. Chang H, Kim W, Park JH, Kim D, Kim CR, Chung S, et al. The occurrence of zearalenone in South Korean feedstuffs between 2009 and 2016. Toxins (Basel). 2017;9(7):223. [Crossref]  [PubMed]  [PMC] 
  50. Kaya S, Pirinçci İ, Bilgili A. Zehirlenmelerin Sebepleri, Tanısı ve Sağaltımı. 2002. [Link] 
  51. Pan P, Ying Y, Ma F, Zou C, Yu Y, Li Y, et al. Zearalenone disrupts the placental function of rats: A possible mechanism causing intrauterine growth restriction. Food Chem Toxicol. 2020;145:111698. [Crossref]  [PubMed] 
  52. Wang J, Xie Y. Review on microbial degradation of zearalenone and aflatoxins. Grain and Oil Science and Technology. 2020;3(3):117-25. [Crossref] 
  53. Mostrom MS, Jacobsen BJ. Ruminant mycotoxicosis: an update. Vet Clin North Am Food Anim Pract. 2020;36(3):745-74. [Crossref]  [PubMed] 
  54. Claeys L, Romano C, De Ruyck K, Wilson H, Fervers B, Korenjak M, et al. Mycotoxin exposure and human cancer risk: A systematic review of epidemiological studies. Compr Rev Food Sci Food Saf. 2020;19(4):1449-64. [Crossref]  [PubMed] 
  55. Bakırcı GT. Tahıl ve tahıl ürünlerinin aflatoksin, okratoksin a, zearalenon, fumonisin ve deoksinivalenol mikotoksinleri yönünden incelenmesi [Determination of aflatoxin, ochratoxin a, zearalenone, fumonisin and deoxynivalenol myctoxins in cereals and cereal based products]. Akademik Gıda. 2014;12(2):46-56. [Link] 
  56. Sun Z, Lian C, Li C, Zheng S. Investigations on organo-montmorillonites modified by binary nonionic/zwitterionic surfactant mixtures for simultaneous adsorption of aflatoxin B1 and zearalenone. J Colloid Interface Sci. 2020;565:11-22. [Crossref]  [PubMed] 
  57. Ismail A, Gonçalves BL, de Neeff DV, Ponzilacqua B, Coppa CFSC, Hintzsche H, et al. Aflatoxin in foodstuffs: Occurrence and recent advances in decontamination. Food Res Int. 2018;113:74-85. [Crossref]  [PubMed] 
  58. Pallaroni L, Björklund E, von Holst C. Alternative extraction methods for Zearalenone: Microwave Assisted Extraction and Accelerated Solvent Extraction. Mycotoxin Res. 2002;18 Suppl 1:74-7. [Crossref]  [PubMed] 
  59. Alexandre APS, Castanha N, Costa NS, Santos AS, Badiale-Furlong E, Augusto PED, et al. Ozone technology to reduce zearalenone contamination in whole maize flour: degradation kinetics and impact on quality. J Sci Food Agric. 2019;99(15):6814-21. [Crossref]  [PubMed] 
  60. Vega MF, Dieguez SN, Riccio B, Aranguren S, Giordano A, Denzoin L, et al. Zearalenone adsorption capacity of lactic acid bacteria isolated from pigs. Braz J Microbiol. 2017;48(4):715-23. [Crossref]  [PubMed]  [PMC] 
  61. Wang N, Wu W, Pan J, Long M. Detoxification Strategies for Zearalenone Using Microorganisms: A Review. Microorganisms. 2019;7(7):208. [Crossref]  [PubMed]  [PMC] 
  62. Ju J, Tinyiro SE, Yao W, Yu H, Guo Y, Qian H, et al. The ability of Bacillus subtilis and Bacillus natto to degrade zearalenone and its application in food. Journal of Food Processing and Preservation. 2019;43(10):14122. [Crossref] 
  63. Wang G, Miao Y, Sun Z, Zheng S. Simultaneous adsorption of aflatoxin B1 and zearalenone by mono- and di-alkyl cationic surfactants modified montmorillonites. J Colloid Interface Sci. 2018;511:67-76. [Crossref]  [PubMed] 
  64. Vega MF, Diéguez SN, Riccio B, Tapia MO, González SN. Zearalenone adsorbent based on a lyophilized indigenous bacterial lactobacillus plantarum strain as feed additive for pigs: a preliminary study in vivo. Curr Microbiol. 2021;78(5):1807-12. [Crossref]  [PubMed] 
  65. Gao X, Xiao ZH, Liu M, Zhang NY, Khalil MM, Gu CQ, et al. Dietary Silymarin Supplementation Alleviates Zearalenone-Induced Hepatotoxicity and Reproductive Toxicity in Rats. J Nutr. 2018;148(8):1209-16. [Crossref]  [PubMed] 
  66. Cao L, Zhao J, Xu J, Zhu L, Rahman SU, Feng S, et al. N-acetylcysteine ameliorate cytotoxic injury in piglets sertoli cells induced by zearalenone and deoxynivalenol. Environ Sci Pollut Res Int. 2021;28(42):60276-89. [Crossref]  [PubMed] 
  67. Kabak B. Bazı mikotoksinlerin detoksifikasyonunda lactobacillus ve bıfıdobacterium suşlarının kullanımı [Doktora tezi]. Adana: Çukurova Üniversitesi; 2007. [Erişim tarihi: 18.11.2024]. [Link] 
  68. Türköz-Bakırcı G. Tahıl ve tahıl ürünlerinin aflatoksin, okratoksin a, zearalenon, fumonisin ve deoksinivalenol mikotoksinleri yönünden incelenmesi [Determination of aflatoxin, ochratoxin a, zearalenone, fumonisin and deoxynivalenol myctoxins in cereals and cereal based products]. Akademik Gıda. 2014;12(2):46-56. [Link] 
  69. European Commission. Commission recommendation of 17 August 2006 on the presence of deoxynivalenol, zearalenone, ochratoxin A, T-2 and HT-2 and fumonisins in products intended for animal feeding. Off J Eur Union. 2006;229:7-8. [Link] 
  70. EFSA (European Food Safety Authority). Scientific opinion on the risk for public health related to the presence of zearalenone in food. Eur. Food Saf. Auth. J. 2011;9:1-124. [Cited: 18.11.2024]. [Crossref] 
  71. Han X, Huangfu B, Xu T, Xu W, Asakiya C, Huang K, et al. Research Progress of Safety of Zearalenone: A Review. Toxins (Basel). 2022;14(6):386. [Crossref]  [PubMed]  [PMC] 
  72. European Food Safety Authority [Internet]. ©European Food Safety Authority, 2017 [Cited: December 5, 2019]. Clarification of some aspects related to genotoxicity assessment. Available from: [Link] 
  73. Resmî Gazete (29.12.2011, Sayı: 28157) Türk Gıda Kodeksi Bulaşanlar Yönetmeliği. Gıdalardaki Bulaşanların Maksimum Limitleri; 2011. Erişim tarihi: 11 Şubat 2022. Erişim linki: [Link] 

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3. SCOPE OF THE SERVICES

3.1. "Turkiye Klinikleri" is completely free to determine the scope and quality of the services via the "SITE".

3.2. To benefit the services of "Turkiye Klinikleri" "SITE", the "USER" must deliver the features that will be specified by "Turkiye Klinikleri". "Turkiye Klinikleri" may change this necessity any time single-sided.

3.3. Not for a limited number, the services "Turkiye Klinikleri" will provide through the "SITE" for a certain price or for free are;

- Providing scientific articles, books and informative publications for health industry.

- Providing structural, statistical and editorial support to article preparation stage for scientific journals.

4. GENERAL PROVISIONS

4.1. "Turkiye Klinikleri" is completely free to determine which of the services and contents provided in the "SITE" will be charged.

4.2. People benefiting from the services provided by "Turkiye Klinikleri" and using the website can use the "SITE" only according to the law and only for personal reasons. Users have the criminal and civil liability for every process and action they take in the "SITE". Every USER agrees, declares and undertakes that they will not proceed by any function or action infringement of rights of "Turkiye Klinikleri"s and/or other third parties', they are the exclusive right holder on usage, processing, storage, made public and revealing any written, visual or auditory information reported to Turkiye Klinikleri" and/or "SITE" to the third parties. "USER" agrees and undertakes that s/he will not duplicate, copy, distribute, process, the pictures, text, visual and auditory images, video clips, files, databases, catalogs and lists within the "SITE", s/he will not be using these actions or with other ways to compete with "Turkiye Klinikleri", directly or indirectly.

4.3. The services provided and the context published within the "SITE" by third parties is not under the responsibility of "Turkiye Klinikleri", institutions collaborated with "Turkiye Klinikleri", "Turkiye Klinikleri" employee and directors, "Turkiye Klinikleri" authorized salespeople. Commitment to accuracy and legality of the published information, context, visual and auditory images provided by any third party are under the full responsibility of the third party. "Turkiye Klinikleri" does not promise and guarantee the safety, accuracy and legality of the services and context provided by a third party.

4.4. "USER"s cannot act against "Turkiye Klinikleri", other "USER"s and third parties by using the "SITE". "Turkiye Klinikleri" has no direct and/or indirect responsibility for any damage a third party suffered or will suffer regarding "USER"s actions on the "SITE" against the rules of the hereby "Terms of Use" and the law.

4.5. "USER"s accept and undertake that the information and context they provided to the "SITE" are accurate and legal. "Turkiye Klinikleri" is not liable and responsible for promising and guaranteeing the verification of the information and context transmitted to "Turkiye Klinikleri" by the "USER"s, or uploaded, changed and provided through the "SITE" by them and whether these information are safe, accurate and legal.

4.6. "USER"s agree and undertake that they will not perform any action leading to unfair competition, weakening the personal and commercial credit of "Turkiye Klinikleri" and a third party,  encroaching and attacking on personal rights within the "SITE" in accordance with the Turkish Commercial Code Law.

4.7. "Turkiye Klinikleri" reserves the right to change the services and the context within the "SITE"  anytime. "Turkiye Klinikleri" may use this right without any notification and timelessly. "USER"s have to make the changes and/or corrections "Turkiye Klinikleri" required immediately. Any changes and/or corrections that are required by "Turkiye Klinikleri", may be made by "Turkiye Klinikleri" when needed. Any harm, criminal and civil liability resulted or will result from changes and/or corrections required by "Turkiye Klinikleri" and were not made on time by the "USER"s belongs completely to the users.

4.8. "Turkiye Klinikleri" may give links through the "SITE" to other websites and/or "CONTEXT"s and/or folders that are outside of their control and owned and run by third parties. These links are provided for ease of reference only and do not hold qualification for support the respective web SITE or the admin or declaration or guarantee for the information inside. "Turkiye Klinikleri" does not hold any responsibility over the web-sites connected through the links on the "SITE", folders and context, the services or products on the websites provided through these links or their context.

4.9. "Turkiye Klinikleri" may use the information provided to them by the "USERS" through the "SITE" in line with the terms of the "PRIVACY POLICY" and "USER CONTRACT". It may process the information or classify and save them on a database. "Turkiye Klinikleri" may also use the USER's or visitor's identity, address, e-mail address, phone number, IP number, which sections of the "SITE" they visited, domain type, browser type, date and time information to provide statistical evaluation and customized services.

5. PROPRIETARY RIGHTS

5.1. The information accessed through this "SITE" or provided by the users legally and all the elements (including but not limited to design, text, image, html code and other codes) of the "SITE" (all of them will be called as studies tied to "Turkiye Klinikleri"s copyrights) belongs to "Turkiye Klinikleri". Users do not have the right to resell, process, share, distribute, display or give someone permission to access or to use the "Turkiye Klinikleri" services, "Turkiye Klinikleri" information and the products under copyright protection by "Turkiye Klinikleri". Within hereby "Terms of Use" unless explicitly permitted by "Turkiye Klinikleri" nobody can reproduce, process, distribute or produce or prepare any study from those under "Turkiye Klinikleri" copyright protection.

5.2. Within hereby "Terms of Use", "Turkiye Klinikleri" reserves the rights for "Turkiye Klinikleri" services, "Turkiye Klinikleri" information, the products associated with "Turkiye Klinikleri" copyrights, "Turkiye Klinikleri" trademarks, "Turkiye Klinikleri" trade looks or its all rights for other entity and information it has through this website unless it is explicitly authorized by "Turkiye Klinikleri".

6. CHANGES IN THE TERMS OF USE

"Turkiye Klinikleri" in its sole discretion may change the hereby "Terms of Use" anytime announcing within the "SITE". The changed terms of the hereby "Terms of Use" will become valid when they are announced. Hereby "Terms of Use" cannot be changed by unilateral declarations of users.

7. FORCE MAJEURE

"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com