Araştırma Makalesi
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1,2 DİMETİLHİDRAZİN İLE OLUŞTURULAN KOLON KANSERİ MODELİNDE ZEOLİT DESTEKLİ BESLENMENİN KANSER GELİŞİMİNE ETKİLERİ

Yıl 2020, Cilt: 83 Sayı: 3, 234 - 240, 29.06.2020

Öz

Amaç: Çevre kirliliği ve 1,2-Dimetilhidrazin (DMH) gibi kimyasal maddelere maruz kalan bitki ve hayvanlara beslenmek insanlarda çeşitli hastalıklara yol açar. Bunlardan biri kolon kanseridir. Yapılan çalışmalarda DMH’in gastrointestinal sistemde birikerek organların fonksiyonlarını bozduğu ve kansere yol açtığı görülmüştür. Zeolit, adsorbsiyon ve iyon değiştirme özelliği nedeniyle birçok alanda kullanılmakla birlikte özellikle tıpta kullanımı da yaygınlaşan aluminyum silikat yapısındaki bir volkanik mineraldir. Zeolitin en bilinen türü olan ve zararsız olduğu kanıtlanan klinoptilolitin, insanlara oral yolla verildiğinde kana geçmediği ve gastrointestinal sistemden feçes olarak atıldığı görülmüştür. Ayrıca insanlara oral yolla verilen klinoptilolitin, kanda çözünmeden gastrointestinal sistemden geçtiği görülmüştür Gereç ve Yöntem: Çalışmada sıçanlarda DMH ile oluşturulan kolon kanserine klinoptilolit ile beslenmenin etkileri araştırılmıştır. Deneyde kontrol, klinoptilolit, DMH ve klinoptilolit+DMH grubu olmak üzere 27 Wistar albino sıçan kullanılmıştır. 16 hafta boyunca DMH grubuna haftada bir DMH enjekte edilirken; klinoptilolit ve klinoptilolit+DMH grupları klinoptilolit ile beslenmiştir. Alınan tüm kolon örnekleri rutin preparasyon işlemlerinden geçirilerek, ışık mikroskobunda incelenmiştir. Ayrıca kolon kanserinde sık rastlanan Wnt-ß-katenin sinyal yoluna özgü ß-katenin antikoru ile immunhistokimyasal boyama yapılarak moleküler değişiklikler belirlenmiştir. Bulgular: DMH grubunda epitel hücrelerinin boylarında kısalma, nükleuslarında şekil değişiklikleri, kripta hücrelerinde büyüme, kan damarı ve bağ doku miktarında artış ve lökosit infiltrasyonu gözlenmiştir. DMH+Klinoptilolit uygulanmasının bu değişiklikleri azalttığı saptanmıştır. ß-katenin reaksiyon şiddeti sırasıyla DMH> klinoptilolit> kontrol > DMH + Klinoptilolit olarak belirlenmiştir. Sonuç: Klinoptilolitin, hücre proliferasyonunu azaltarak DMH’nin olası toksik etkilerini azalttığı düşünülmektedir.

Destekleyen Kurum

İstanbul Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi

Proje Numarası

25342

Kaynakça

  • 1. Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RG, Barzi A, et al. Colorectal cancer statistics. CA Cancer J Clin 2017;67(3):177-93.
  • 2. Fernia AP, Caderni G. Rodents Models of Colon Carcinogenesis for the Study of Chemopreventive Activity of Natural Products. Planta Med 2008;74:1602-7.
  • 3. Rosenberg DW, Giardina C, Tanaka T. Mouse models for the study of colon carcinogenesis. Carcinogenesis 2009;30(2):183-96.
  • 4. Irving AA, Yoshimi K, Hart ML, Parker T, Clipson L, Ford MR, Kuramoto T, Dove WF, Amos-Landgraf JM. The utility of Apc-mutant rats in modeling human colon cancer. Dis Model Mech 2014;7(11):1215-25.
  • 5. Lorenz E, Stewart HL. Intestinal carsinoma and other lesion in mice following oral administration of 1,2,5,6- dibenzathracene and 20-methylcholanthrene. J Natl Cancer 1941;1(1):17-40.
  • 6. Walpole AL, Williams M, Roberts DC. The carsinogenic action of 4- aminodiphenyl and 3,2 dimethyl 4-aminodiphenly. Br J Ind Med 1952;9:255-263.
  • 7. Laquer GL, Mickelson O, Whiting MG, Kurland LT. Carsinogenic properties of nuts from cycas circinalis indigenous to Guam. J Natl Cancer Inst 1963;31:919-23.
  • 8. Rosenberg DW, Giardina C, Tanaka T. Mouse models for the study of colon carcinogenesis. Carcinogenesis 2009; 30(2):183-96.
  • 9. Perše M, Cerar A. Morphological and molecular alterations in 1,2 dimethylhydrazine and azoxymethane induced colon carcinogenesis in rats. J Biomed Biotechnol 2011;473964.
  • 10. Heijstek MW, Kranenburg O, Rinkes IB. Mouse Models of Colorectal Cancer and Liver Metastases. Dig Surg 2005;22:16-25.
  • 11. Mastinu A, Kumar A, Maccarinelli G, Bonini SA, Premoli M, Aria F. et al. Zeolite Clinoptilolite: Therapeutic Virtues of an Ancient Mineral. Molecules 2019;24(8):1517.
  • 12. Inglezakis V, Loizidou MD, Grigoropoulou HP. Ion Exchange of Pb2+, Cu2+, Fe3+, and Cr3+ on Natural Clinoptilolite: Selectivity Determination and Influence of Acidity on Metal Uptake. J Colloid Interf Sci 2003;261:49-54.
  • 13. Mihoslov M, Vecerek V, Mas N. Effect of the Feed Additive Clinoptilolite (ZeoFeed) on Nutrient Metabolism and Production Performance of Laying Hens. Acta Vet Brmo 2010;79: 29-34.
  • 14. Grce M, Pavelic K. Antiviral Properties of Clinoptilolite. Micropor Mesopor Mat 2005;79:165-9.
  • 15. Kleiner M, Flegar Z, Zadro R. The Effect of the Zeolite Clinoptilolite on Serum Chemistry and Hematopoiesis in Mice. Food Chem Toxicol 2001;39:717-27.
  • 16. Mück D, Pivac N. The Effect of Natural Clinoptilolite on The Serotonergic Receptors in The Brain of Mice with Mammary Carcinoma, Life Sci 2003;73:2059-69.
  • 17. Pavelić K, Hadzija M, Bedrica L, Pavelić J, Dikić I, Katić M, et al. Natural zeolite clinoptilolite: new adjuvant in anticancer therapy. J Mol Med Berl 2001;78:708-20.
  • 18. Pavelic K, Katic M, Sverko V. Immunostimulatory Effect of Natural Clinoptilolite as a Possible Mechanism of its Antimetastatic Ability. J Cancer Resclin Oncol 2002;128:37-44.
  • 19. Pavelic K, Hadzija M, Bedrica L. Natural Zeolite Clinoptilolite: New Adjuvant in Anticancer Therapy. J Mol Med 2001;78:708-20.
  • 20. Genuis JS. Elimination of Persistent Toxicants from The Human Body. Hum Exp Toxicol 2011;30(1):3-18.
  • 21. Flowers JL, Lonkey SA, Deitsch JE. Clinical Evidence Supporting The Use of an Activated Clinoptilolite Suspension as an Agent to Increase Urinary Excretion of Toxic Heavy Metals. J Nutr Diet Supp 2009;1(4):11-8.
  • 22. Rodriguez-Fuentes G, Barrios MA, Iraizoz A, Perdomo I, Cedre B. Enterex: Anti-diarrheic Drug Based On Purified Natural Clinoptilolite. Zeolites 1997;19:441-8.
  • 23. Lecarpentier Y, Claes V, Vallée A, Hébert JL. Interactions between PPAR gamma and the canonical Wnt/beta-catenin pathway in type 2 diabetes and colon cancer. PPAR research 2017;2017:1-9.
  • 24. He T-C, Chan TA, Vogelstein B, Kinzler KW. PPAR delta is an APC regulated target of nonsteroidal anti-inflammatory drugs. Cell 1999;99:335-45.
  • 25. Tetsu O, McCormick F. b-Catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 1999;39:422-6.
  • 26. Heijstek MW, Kranenburg O, Borel Rinkes IH. Mouse models of colorectal cancer and liver metastases. Dig Surg 2005;22(1-2):16-25.
  • 27. Harris CC, Autrup H, Stoner GD, McDowell EM, Trump BF, Schafer P. Metabolism of dimethylnitrosamine and 1,2-dimethylhydrazine in cultured human bronchi. Cancer Res 1977;37:2309-11.
  • 28. Kuraguchi M, Cook H, Williams ED, Thomas GA. Differences in susceptibility to colonic stem cell somatic mutation in three strains ofmice. J Pathol 2001;193(4):517-21.
  • 29. Thulesen J, Hartman B, Hare KJ, Kissow H, Ørskov C, Holst JJ. Glucagon-like peptide 2 (GLP-2) accelerates the growth of colonic neoplasms in mice. Gut 2004;53(8):1145-50.
  • 30. Maden tetkik arama (MTA). Zeolit. (Cited 2019, August 30). Available from: URL: http://www.mta.gov.tr/v3.0/bilgimerkezi/zeolit

THE EFFECTS OF ZEOLITE SUPPORTED NUTRITION ON CANCER DEVELOPMENT IN THE 1,2 DYMETHYLHYDRASIN INDUCED -COLON CANCER MODEL

Yıl 2020, Cilt: 83 Sayı: 3, 234 - 240, 29.06.2020

Öz

Objective: Environmental pollution and nutrition with plants and animals exposed to chemical substances such as 1,2-Dimethylhydrazine (DMH) causes many diseases. Colon cancer is one of them. DMH has been found to accumulate in the gastrointestinal tract, impairing the functions of its organs and causing cancer. Zeolite is a volcanic mineral which contains aluminum silicate, which is used in many areas due to its absorption and ion exchange capability, and which has had widespread medical use in recent years. Clinoptilolite, the most well-known species of zeolite, proved to be harmless, did not enter the blood when administered orally to humans and was excreted as a faeces from the gastrointestinal tract. In addition, clinoptilolite administered orally to humans passes through the gastrointestinal tract without dissolving in the blood. Material and Method: The aim of this study was to investigate the effects of clinoptilolite nutrition on colon cancer induced by DMH in rats. The rats were divided into four experimental groups which were control, clinoptilolite, DMH, and clinoptilolite+DMH using a total of 46 Wistar albino rats. Rats of DMH and clinoptilolite + DMH groups were injected withDMH subcutaneously once a week for 16 weeks at a dose of 20 mg/kg and also clinoptilolite and clinoptilolite+DMH groups were fed a diet with 50% clinoptilolite for eight months. Results: Molecular changes were examined by immunohistochemical staining in colon tissue samples with ß-catenin antibody specific for Wnt-ß-catenin signaling pathway, which is common in colon cancer. The reaction intensity of ß-catenin was determined as DMH> clinoptilolite control> DMH + clinoptilolite, respectively. Conclusion: We may think that clinoptilolite reduces the potential toxic effects of DMH by decreasing cell proliferation.

Proje Numarası

25342

Kaynakça

  • 1. Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RG, Barzi A, et al. Colorectal cancer statistics. CA Cancer J Clin 2017;67(3):177-93.
  • 2. Fernia AP, Caderni G. Rodents Models of Colon Carcinogenesis for the Study of Chemopreventive Activity of Natural Products. Planta Med 2008;74:1602-7.
  • 3. Rosenberg DW, Giardina C, Tanaka T. Mouse models for the study of colon carcinogenesis. Carcinogenesis 2009;30(2):183-96.
  • 4. Irving AA, Yoshimi K, Hart ML, Parker T, Clipson L, Ford MR, Kuramoto T, Dove WF, Amos-Landgraf JM. The utility of Apc-mutant rats in modeling human colon cancer. Dis Model Mech 2014;7(11):1215-25.
  • 5. Lorenz E, Stewart HL. Intestinal carsinoma and other lesion in mice following oral administration of 1,2,5,6- dibenzathracene and 20-methylcholanthrene. J Natl Cancer 1941;1(1):17-40.
  • 6. Walpole AL, Williams M, Roberts DC. The carsinogenic action of 4- aminodiphenyl and 3,2 dimethyl 4-aminodiphenly. Br J Ind Med 1952;9:255-263.
  • 7. Laquer GL, Mickelson O, Whiting MG, Kurland LT. Carsinogenic properties of nuts from cycas circinalis indigenous to Guam. J Natl Cancer Inst 1963;31:919-23.
  • 8. Rosenberg DW, Giardina C, Tanaka T. Mouse models for the study of colon carcinogenesis. Carcinogenesis 2009; 30(2):183-96.
  • 9. Perše M, Cerar A. Morphological and molecular alterations in 1,2 dimethylhydrazine and azoxymethane induced colon carcinogenesis in rats. J Biomed Biotechnol 2011;473964.
  • 10. Heijstek MW, Kranenburg O, Rinkes IB. Mouse Models of Colorectal Cancer and Liver Metastases. Dig Surg 2005;22:16-25.
  • 11. Mastinu A, Kumar A, Maccarinelli G, Bonini SA, Premoli M, Aria F. et al. Zeolite Clinoptilolite: Therapeutic Virtues of an Ancient Mineral. Molecules 2019;24(8):1517.
  • 12. Inglezakis V, Loizidou MD, Grigoropoulou HP. Ion Exchange of Pb2+, Cu2+, Fe3+, and Cr3+ on Natural Clinoptilolite: Selectivity Determination and Influence of Acidity on Metal Uptake. J Colloid Interf Sci 2003;261:49-54.
  • 13. Mihoslov M, Vecerek V, Mas N. Effect of the Feed Additive Clinoptilolite (ZeoFeed) on Nutrient Metabolism and Production Performance of Laying Hens. Acta Vet Brmo 2010;79: 29-34.
  • 14. Grce M, Pavelic K. Antiviral Properties of Clinoptilolite. Micropor Mesopor Mat 2005;79:165-9.
  • 15. Kleiner M, Flegar Z, Zadro R. The Effect of the Zeolite Clinoptilolite on Serum Chemistry and Hematopoiesis in Mice. Food Chem Toxicol 2001;39:717-27.
  • 16. Mück D, Pivac N. The Effect of Natural Clinoptilolite on The Serotonergic Receptors in The Brain of Mice with Mammary Carcinoma, Life Sci 2003;73:2059-69.
  • 17. Pavelić K, Hadzija M, Bedrica L, Pavelić J, Dikić I, Katić M, et al. Natural zeolite clinoptilolite: new adjuvant in anticancer therapy. J Mol Med Berl 2001;78:708-20.
  • 18. Pavelic K, Katic M, Sverko V. Immunostimulatory Effect of Natural Clinoptilolite as a Possible Mechanism of its Antimetastatic Ability. J Cancer Resclin Oncol 2002;128:37-44.
  • 19. Pavelic K, Hadzija M, Bedrica L. Natural Zeolite Clinoptilolite: New Adjuvant in Anticancer Therapy. J Mol Med 2001;78:708-20.
  • 20. Genuis JS. Elimination of Persistent Toxicants from The Human Body. Hum Exp Toxicol 2011;30(1):3-18.
  • 21. Flowers JL, Lonkey SA, Deitsch JE. Clinical Evidence Supporting The Use of an Activated Clinoptilolite Suspension as an Agent to Increase Urinary Excretion of Toxic Heavy Metals. J Nutr Diet Supp 2009;1(4):11-8.
  • 22. Rodriguez-Fuentes G, Barrios MA, Iraizoz A, Perdomo I, Cedre B. Enterex: Anti-diarrheic Drug Based On Purified Natural Clinoptilolite. Zeolites 1997;19:441-8.
  • 23. Lecarpentier Y, Claes V, Vallée A, Hébert JL. Interactions between PPAR gamma and the canonical Wnt/beta-catenin pathway in type 2 diabetes and colon cancer. PPAR research 2017;2017:1-9.
  • 24. He T-C, Chan TA, Vogelstein B, Kinzler KW. PPAR delta is an APC regulated target of nonsteroidal anti-inflammatory drugs. Cell 1999;99:335-45.
  • 25. Tetsu O, McCormick F. b-Catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 1999;39:422-6.
  • 26. Heijstek MW, Kranenburg O, Borel Rinkes IH. Mouse models of colorectal cancer and liver metastases. Dig Surg 2005;22(1-2):16-25.
  • 27. Harris CC, Autrup H, Stoner GD, McDowell EM, Trump BF, Schafer P. Metabolism of dimethylnitrosamine and 1,2-dimethylhydrazine in cultured human bronchi. Cancer Res 1977;37:2309-11.
  • 28. Kuraguchi M, Cook H, Williams ED, Thomas GA. Differences in susceptibility to colonic stem cell somatic mutation in three strains ofmice. J Pathol 2001;193(4):517-21.
  • 29. Thulesen J, Hartman B, Hare KJ, Kissow H, Ørskov C, Holst JJ. Glucagon-like peptide 2 (GLP-2) accelerates the growth of colonic neoplasms in mice. Gut 2004;53(8):1145-50.
  • 30. Maden tetkik arama (MTA). Zeolit. (Cited 2019, August 30). Available from: URL: http://www.mta.gov.tr/v3.0/bilgimerkezi/zeolit
Toplam 30 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Sağlık Kurumları Yönetimi
Bölüm ARAŞTIRMA
Yazarlar

Serap Kuruca 0000-0002-5566-7844

Kadriye Akgün Dar Bu kişi benim 0000-0003-2060-1199

Ayşegül Kapucu Bu kişi benim 0000-0002-0946-1407

Dilşad Özerkan Bu kişi benim 0000-0002-0556-3879

Proje Numarası 25342
Yayımlanma Tarihi 29 Haziran 2020
Gönderilme Tarihi 14 Mayıs 2019
Yayımlandığı Sayı Yıl 2020 Cilt: 83 Sayı: 3

Kaynak Göster

APA Kuruca, S., Akgün Dar, K., Kapucu, A., Özerkan, D. (2020). 1,2 DİMETİLHİDRAZİN İLE OLUŞTURULAN KOLON KANSERİ MODELİNDE ZEOLİT DESTEKLİ BESLENMENİN KANSER GELİŞİMİNE ETKİLERİ. Journal of Istanbul Faculty of Medicine, 83(3), 234-240.
AMA Kuruca S, Akgün Dar K, Kapucu A, Özerkan D. 1,2 DİMETİLHİDRAZİN İLE OLUŞTURULAN KOLON KANSERİ MODELİNDE ZEOLİT DESTEKLİ BESLENMENİN KANSER GELİŞİMİNE ETKİLERİ. İst Tıp Fak Derg. Haziran 2020;83(3):234-240.
Chicago Kuruca, Serap, Kadriye Akgün Dar, Ayşegül Kapucu, ve Dilşad Özerkan. “1,2 DİMETİLHİDRAZİN İLE OLUŞTURULAN KOLON KANSERİ MODELİNDE ZEOLİT DESTEKLİ BESLENMENİN KANSER GELİŞİMİNE ETKİLERİ”. Journal of Istanbul Faculty of Medicine 83, sy. 3 (Haziran 2020): 234-40.
EndNote Kuruca S, Akgün Dar K, Kapucu A, Özerkan D (01 Haziran 2020) 1,2 DİMETİLHİDRAZİN İLE OLUŞTURULAN KOLON KANSERİ MODELİNDE ZEOLİT DESTEKLİ BESLENMENİN KANSER GELİŞİMİNE ETKİLERİ. Journal of Istanbul Faculty of Medicine 83 3 234–240.
IEEE S. Kuruca, K. Akgün Dar, A. Kapucu, ve D. Özerkan, “1,2 DİMETİLHİDRAZİN İLE OLUŞTURULAN KOLON KANSERİ MODELİNDE ZEOLİT DESTEKLİ BESLENMENİN KANSER GELİŞİMİNE ETKİLERİ”, İst Tıp Fak Derg, c. 83, sy. 3, ss. 234–240, 2020.
ISNAD Kuruca, Serap vd. “1,2 DİMETİLHİDRAZİN İLE OLUŞTURULAN KOLON KANSERİ MODELİNDE ZEOLİT DESTEKLİ BESLENMENİN KANSER GELİŞİMİNE ETKİLERİ”. Journal of Istanbul Faculty of Medicine 83/3 (Haziran 2020), 234-240.
JAMA Kuruca S, Akgün Dar K, Kapucu A, Özerkan D. 1,2 DİMETİLHİDRAZİN İLE OLUŞTURULAN KOLON KANSERİ MODELİNDE ZEOLİT DESTEKLİ BESLENMENİN KANSER GELİŞİMİNE ETKİLERİ. İst Tıp Fak Derg. 2020;83:234–240.
MLA Kuruca, Serap vd. “1,2 DİMETİLHİDRAZİN İLE OLUŞTURULAN KOLON KANSERİ MODELİNDE ZEOLİT DESTEKLİ BESLENMENİN KANSER GELİŞİMİNE ETKİLERİ”. Journal of Istanbul Faculty of Medicine, c. 83, sy. 3, 2020, ss. 234-40.
Vancouver Kuruca S, Akgün Dar K, Kapucu A, Özerkan D. 1,2 DİMETİLHİDRAZİN İLE OLUŞTURULAN KOLON KANSERİ MODELİNDE ZEOLİT DESTEKLİ BESLENMENİN KANSER GELİŞİMİNE ETKİLERİ. İst Tıp Fak Derg. 2020;83(3):234-40.

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