İyonize Radyasyonun Neden Olduğu Ovaryum Hasarına Karşı Curcuminin Koruyucu Etkisinin Morfolojik ve İmmünohistokimyasal Olarak İncelenmesi

Yıl 2018, Cilt: 9 Sayı: 2, 102 - 111, 01.08.2018

Kanat Gülle , İbrahim Pala Meryem Akpolat , Bekir Hakan Bakkal

https://doi.org/10.22312/sdusbed.301632

Öz

Çalışmamızda,
iyonize radyasyonun folliküler atrezi üzerine etkilerini göstererek, oluşacak
hasarlara karşı curcuminin koruyucu etkisinin olup olmadığını ve hücre
çekirdeklerinde meydana gelen DNA hasarını tamir eden Poli
(ADP-riboz)polimeraz-1 enziminin immünohistokimyasal boyama yöntemiyle
gösterilmesi amaçlandı.

            Çalışmamız için seçilen dişi
sıçanlar, biri kontrol olmak üzere toplam 4 gruba ayrıldı. Radyasyon hasarı
oluşturmak amacıyla kontrol ve curcumin grubu dışındaki deneklere tek doz tüm
vücut 8.3 Gy iyonize radyasyon uygulandı. Curcumin ve radyasyon+curcumin grubu
deneklere; ışınlamadan 7 gün önce başlayarak günde 100 mg/kg curcumin oral
yoldan verildi. Işınlamadan sonraki 4. günde deneklerden anestezi altında
ovaryum dokuları alınarak mikroskobik incelemeler için işlemlendirildi.

            Radyasyon uygulamasından 4 gün sonra
alınan ovaryum dokularının kesitlerini incelediğimizde, ışınlanmış gruplardaki
atretik özellik gösteren folliküller sayıca fazlaydı. Radyasyon ile ışınlanan
curcumin tedavili grupta ise atretik follikül oranı radyasyon grubuna göre daha
düşüktü. Curcumin ile tedavi edilen grupta, curcuminin radyasyona bağlı meydana
gelen hasarları kısmen engellediği tespit edildi.

Anahtar Kelimeler

İyonize radyasyon, Follikülogenezis, Curcumin, PARP1

Kaynakça

• 1. Baker, T.G. (1963) A Quantitative and Cytological Study of Germ Cells in Human Ovaries. Proc R Soc Lond B Biol Sci. 158: 417-433.
• 2. Faddy, M.J., R.G. Gosden, A. Gougeon, S.J. Richardson and J.F. Nelson (1992) Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. Hum Reprod .(7)10:1342-1346.
• 3. Townson, D.H. and C.M.H. Combelles. (2012) Ovarian Follicular Atresia. In Tech 43-76.
• 4. Lee, C.J., Park, H.H., Do. B.R., Yoon, Y.D., Kim. J.K. (2000) Natural and radiation – induced degeneration of primordial and primary follicles in Mouse ovary. Ani. Repro. Sci 59, 109-117.
• 5. Kim, J.K., Lee C.J, Song K.W.,et al (1999) γ-Radiation accelerates ovarian follicular atresia in immature mice. In Vivo 13(1): 21-24).
• 6. Byrne, J. (1999) Long-term genetic and reproductive effects of ionizing radiation and chemotherapeutic agents on cancer patients and their offspring. Teratology 59:210-215.
• 7. Meirow, D., and Nugent. D. (2001) The effects of radiotherapy and chemotherapy on female reproduction. Human Reproduction Update 7(6): 535-543.
• 8. Chemaitilly, W., Mertens, A.C., Mitby, P., Whitton, J., Stovall, M., Yasui, Y., Robison, L.L, Sklar, C.A. (2006) Acute ovarian failure in the childhood cancer survivor study. J. Clin Endocrinol Metab 91:1723-1728.
• 9. Howell, S., Shalet, S. (1998) Gonodal damage from chemotherapy and radiotherapy. Endocrinol Metab Clin North Am 27:927-943.
• 10. Nicosia, S.V., Matus-Riley, V., Meadows, A.T. (1985) Gonodal effects of cancer therapy in girls. Cancer 55:2364-2372.
• 11. Choudhary, D. (1999) Modulation of radioresponse of glyoxalase system by curcumin. Journal of Ethnopharmacology; 46:1-7.
• 12. Jeggo, P.A. (1998) DNA repair: PARP-another guardian genome? Curr Biol 8:49-51.
• 13. Burkle, A. (2005) Poly (ADP ribose): The most elaborate metabolite of NAD+. FEBS Journal 272:4576–4589.
• 14. Quesada, R.C., Gamez, J.A.M.,Oliva, D.M., Peralta, A., Valenzuela M.T., Romero, R.M., Perez R.Q., De Murcia, J.M., De Murcia, G., De Almodovar, M.R., and Oliver F.J. (2007) Interaction between ATM and PARP-1 in response to DNA damage and sensitization of ATM deficient cells through PARP inhibition. BMC Molecular Biology 8:29.
• 15. Schreiber, V., Dantzer, F., Amé, J. C., and de Murcia, G. (2006) Poly(ADP-ribose): novel functions for an old molecule. Nat. Rev. Mol. Cell Biol. 7, 517-528.
• 16. Bouchard, V.J., Rouleau, M., and Poirier, G. G. (2003) PARP-1, a determinant of cell survival in response to DNA damage. Exp. Hematol. 31, 446-454.
• 17. Ammon, H.P., Wahl, M.A. (1991) Pharmacology of Curcuma longa. Planta Medica 57(1): 1–7.
• 18. Eigner, D., Scholz, D. (1999) Ferula asafoetida and Curcuma longa in traditional medical treatment and diet in Nepal. Journal of Ethnopharmacology 67(1): 1–6.
• 19. Akpolat, M., Topçu Tarladaçalışır, Y., Uz, Y.H., Sapmaz, M.M., Kızılay, G. (2010) Kanser Tedavisinde Curcuminin Yeri. Yeni Tıp Dergisi 27:142-147.
• 20. Tilly, J.L. (2003) Ovarian follicle counts not as simple as 1, 2, 3. Reprod Biol Endocrinol 1:11.
• 21. Srinivasan, M., Ram, Sudheer., Raveendran, P.K., Raghu, K.P., Sudhakaran, P.R., Menon, V.P. (2007) Modulatory effects of curcumin on γ- radiation-induced cellular damage in primary culture of isolated rat hepatocytes. Environmental Toxicology and Pharmacology 24:98-105.
• 22. Jagetia, G.C., Rajanikant, G.K. (2004) Role of curcumin, a Naturally occuring phenolic compound of Turmeric in Accelerating the repair of excision wound, in mice whole-body exposed to various doses of γ- radiation. Journal of Surgical Research 120:127-138.
• 23. Thibaud, E., Rodriquez, M.K., Trivin, C. (1998) Ovarian function after bone marrow transplantation during childhood. Bone Marrow Transplant 22:989-994.
• 24. Devine, P.J., Payne, C.M., McCuskey, M.K., Hoyer, P.B. (2000) Ultrastructural evaluation of oocytes during atresia in rat ovarian follicles. Biol Reprod. 65(5):1245- 52.
• 25. Kim, J.K., Lee, C.J. (2000) Effect of exogenous melatonin on the ovarian follicles in γ- irradiated mouse. Mutat Res 449:33-39.
• 26. Aktas, C., Kanter, M., Kocak, Z. (2011) Antiapoptotic and proliferative activity of curcumin on ovarian follicles in mice exposed to whole body ionizing radiation. Toxicology and Industrial Health 1- 12.
• 27. Mole, R.H., Papworth, D.G. (1966) The sensitiviy of rat oocytes to X-rays. Int Radiat Biol 6:609-15.
• 28. Metindir, J., Bozkurt, C. (2005) Kanser tedavilerinin over fonksiyonlarına etkisi ve fertilitede koruyucu yaklaşımlar. J Turkish German Gynecol Assoc 6(1):23-29.
• 29. Uzal, C., Çaloğlu, M. (2002) Kanser etyolojisinde iyonizan radyasyonun yeri. Trakya Üniv Tıp Fak Derg 19:177-182.
• 30. Kelle, İ. (2008) Radyoprotektif Etkili Ajanlar. Dicle Tıp Dergisi 35(1):69-76.
• 31. Antunes, L.M.G., Araujo, M.C.P., Dia, P.B.L., Takahashi, C. (2005) Effect of H2O2, Fe+2 and Fe+3 on curcumin-induced chrosomal aberrations in CHO cells. Genet. Mol. Biol. 28:161-164.
• 32. Khopde, S.M., Priyadarsini, K.I., Guha, S.N., Satav, J.G., Venkatesan, P., Rao, M.N.A. (2000) Inhibition of radiation-induced lipid peroxidation by tetrahydrocurcumin: Possible mechanisms by pulse radiolysis. Biosci Biotechnol Biochem 64(3):503-509.
• 33. Huang, M.T., Lou, Y.R., Me, W., Newmark, H.L., Reuhl, K.R., Conney ,H. (1994) Inhibitory effects of dietary curcumin on forestomach, dueodonal an colon carcinogenesis in mice. Cancer Res 54:5841-7.
• 34. Thresiamma, K.C., George, J., Kuttan, R. (1996) Protective effect of curcumin ellagic acid and bixin on radiation induced toxicitiy. J Exp Biol 34:845-7.
• 35. Kanter, M., Aktaş, C., and Erboğa, M. (2012) Curcumin attenuates testicular damage, apoptotic germ cell death, and oxidative stres in streptozotocin-induced diabetic rats. Mol Nutr Food Res 56:1-8.
• 36. Reddy, P., Lokesh, B.R. (1994) Studies on the inhibitory effects of curcumin and eugenol on the formation of reactive oxygen species and the oxidation of ferrous iron. Mol Cell Bichem 137:1-8.
• 37. Qian, H., Xu, J., Lalioti, M.D., Gulle, K., Sakkas, D. (2010) Oocyte numbers in the mouse increase after treatment with 5-Aminoisoquinolinone: A potent inhibitor of poly(ADP-ribosyl)ation. Biology of Reproduction 82:1000-1007.
• 38. Tekcan, M., Koksal, T.K., Tasatargil, A., Kutlu, O., Gungor, E., Celik-Ozenci, C. (2012) Potential role of poly(ADP-ribose) polymerase activation in the pathogenesis of experimental left varicocele. Journal of Andrology. 33:122-132.
• 39. Ossovskaya, V., Chou, K.I., Kaldjian, E.P., Alvares, C., Sherman, B.M. (2010) Upregulation of Poly (ADP-Ribose) Polymerase-1 (PARP1) in Triple-Negative Breast Cancer and Other Primary Human Tumor Types. Genes & Cancer. 1:812-821.
• 40. Bakondi, E. (2003) Alterations in PARP metabolism and calcium homeostasis in oxidatively stressed HaCaT and Mouse macrophage cell lines. University of Debrecen.
• 41. Tezcan, G. (2008) PARP-1 ve XRCC1 polimorfizmlerinin astım’da DNA onarım mekanizması ile olan ilişkisinin araştırılması. İstanbul Üniversitesi İstanbul.
• 42. Di Meglio, S., Denegri, M., Vallefuoco, S., Tramontano, F., Scovassi, AI., Quesada, P. (2003) Poly(ADPR) polymerase-1 and poly(ADPR) glycohydrolase level and distribution in differentiating rat germinal cells. Molecular and Cellular Biochemistry 248:85-91.
• 43. Atorino, L., Di Meglio, S., Farina, B., Jones, R., Quesada, P. (2001) Parp requirement of rat germinal cells in the recovery from DNA damage induced by gamma irradiation and H2O2 treatment. Eur J Cell Biol 80:222-229.
• 44. De Murcia, J.M., Neidergang, C., Trucco, C., Ricoul, M., Dutrillaux, B., Mark, M., Oliver, F.J., Masson, M., Dierich, A., Lemeur, M., Waltzinger, C., Chambon, P.P., De Murcia, G. (1997) Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells. Proc Natl Acad Sci 94:7303-7307.