Çiğdem ELMAS, Deniz ERDOĞAN, Güleser GÖKTAŞ, CANAN ULUOĞLU, Yıldız GÜNEY, GÜL ÖZBEY, Ayşe HİÇSÖNMEZ, Berna YÜCEL, Seçil ÖZKAN, DİLA ŞENER

İyonize radyasyon uygulaması yapılmış rat pineal bezi üzerinde melatoninin koruyucu etkisi var mıdır? kronobiyolojik ve elektron mikroskobik çalışma

Çalışmamızda, tüm vücuda uygulanan iyonize radyasyonun, sıçan pineal bezinde yaptığı ince yapı düzeyindeki dejeneratif değişiklikler ve melatoninin (MLT) olası koruyucu etkisi, elektron mikroskobik ve kronobiyolojik olarak araştırılmıştır. Bu amaçla toplam 48 adet erkek Wistar albino sıçan kullanılmıştır. Araştırmamızda, kontrol (K), tüm vücut radyasyon (TVR) ve tüm vücut radyasyon+melatonin (TVR+MLT) grupları, sabah ve akşam olmak üzere günün iki farklı saatinde çalışılarak toplam 6 deney grubu oluşturulmuştur. TVR grubundaki deneklere 8 Gy subletal (öldürücü dozun altında) radyasyon, 60Co (sağaltıcı aygıt Chisostat, açığa çıkarma hızı 0.29 Gy.dak-1) kaynağı ile deneklerin derilerinden 80 cm uzaklıktan, akşam (21.00) ve sabah (09.00) uygulanmıştır. MLT ise radyasyon verilmesinden once (10 mg/kg), hemen sonra (20 mg/kg) ve 24 saat sonra (10 mg/kg) olmak üzere intraperitoneal olarak uygulanmıştır. İnce yapı düzeyinde mitokondriyon ve pinealosit çapları ölçülmüş ve organel özellikleri histolojik olarak değerlendirilmiştir. Radyasyon uygulamasından en çok akşam grubunun etkilendiği ve melatoninin bu dejeneratif etkileri ortadan kaldırdığı, çok büyük bir farklılık olmamakla beraber TVR+MLT sabah grubunun daha iyi durumda olduğu saptanmış ancak, iki melatonin grubu arasında anlamlı bir farklılık belirlenmemiştir. Farklı organeller açısından olsa da, sıçan pineal bezinin, iyonize radyasyonun neden olduğu zedelenmeye akşam daha duyarlı olduğu, buna karşın, MLT uygulamasının oluşturduğu sağaltıcı etkide, sabah ve akşam arasında bir fark olmadığı düşünülmüştür.

Anahtar Kelimeler:

melatonin, hayvan modelleri, hormonal kontrol, sıçan, hormon salınımı, ışınlama, pineal cisim

Has melatonin protective effects on irradiated rat pineal gland? cronobiologic and electron microscobic study

In this study, effect of whole body ionizing irradiation on pineal gland in rats and possible protective effects of melatonin (MLT) were investigated by chronobiological and electron microscopic methods. For this purpose 48 male Wistar rats consisting of 6 group that were; control (morning and evening groups), whole body irradiation (WBI) (morning and evening groups), whole-body irradiation+melatonin (WBI + MLT) (morning and evening groups) were used. WBI group exposed to sublethal (below the lethal dose) irradiation dose of 8 Gy using 60Co source (Chisostat therapeutic device, revealing rate 0.29 Gy.dak-1) focusing of 80 cm away from the skin in morning (09.00 am) and evening (09.00 pm). Melatonin administered intraperitoneally immediately before (10 mg/kg), after (20 mg/kg) and 24 h after (10 mg/kg) whole body irradiated rats. Ultrastructurally, mitochondria and pinealocyte diameters measured and organelle properties were evaluated histologically. Evening groups were the most affected groups by application of irradiation. However, melatonin administration considerably inhibited these degenerative changes. Although there was not any significant differences between two melatonin groups, WBI + MLT morning group was better than that of evening group. We thought that, although in different organelles, rat pineal gland was more sensitive to irradiation in evening than morning. However, we did not find any significant difference between therapeutic effect of MLT administration in morning and evening groups.

Keywords:

melatonin, animal models, hormonal control, rats, hormone secretion, irradiation, pineal body,

PDF

___

1. Beyer CE, Steketee JD, Saphier D: Antioxidant properties of melatonin-an emerging mystery. Biochem Pharmacol, 56 (10): 1265-1272, 1998.
2. Buijs RM, Wortel J, Van Heerikhuize JJ, Feenstra MG, Ter Horst GJ, Romijn HJ, Kalsbeek A: Anatomical and functional demonstration of a multisynaptic suprachiasmatic nucleus adrenal (cortex) pathway. Eur J Neurosci, 11 (5): 1535-1544, 1999.
3. Pevet P, Challet E: Melatonin: both master clock output and internal time-giver in the circadian clocksnetwork. J Physiol Paris, 105 (4-6): 170-182, 2011.
4. Challet E: Interactions between light, mealtime and calorie restriction to control daily timing in mammals. J Comp Physiol B, 180 (5): 631-644, 2010.
5. Perreau-Lenz S, Kalsbeek A, Van Der Vliet J, Pévet P, Buijs RM: In vivo evidence for a controlled offset of melatonin synthesis at dawn by thesuprachiasmatic nucleus in the rat. Neuroscience, 130 (3): 797-803, 2005.
6. Mansour HH: Protective role of carnitine ester against radiation-induced oxidative stress in rats. Pharmacol Res, 54 (3): 165-171, 2006.
7. Sonmez OF, Odaci E, Bas O, Kaplan S: Purkinje cell number decreases in the adult female rat cerebellum following exposure to 900 MHz electromagnetic field. Brain Res, 1356, 95-101, 2010.
8. Çenesiz M, Atakişi O, Akar A, Önbilgin G, Ormancı N: Eff ects of 900 and 1800 MHz electromagnetic field application on electrocardiogram, nitric oxide, total antioxidant capacity, total oxidant capacity, total protein, albumin and globulin levels in guinea pigs. Kafkas Univ Vet Fak Derg, 17 (3): 357-362, 2011.
9. Carocho M, Ferreira IC: A review on antioxidants, prooxidants and related controversy: natural and syntheticcompounds, screening and analysis methodologies and future perspectives. Food Chem Toxicol, 51, 15-25, 2012.
10. Bharti VK, Srivastava RS, Subramaian P, Warren Spence D, Pandi-Perumal SR, Brown GM: Cerebral epiphyseal proteins and melatonin modulate the hepatic and renalantioxidant defense of rats. Int J Nephrol, 2011:142896. Epub: May 26, 2011.
11. Odaci E, Kaplan S: Melatonin and nevre regeneration. Int Rev Neurobiol, 87, 317-335, 2009.
12. Turgut M, Uyanıkgil Y, Baka M, Tunç AT, Yavaşoğlu A, Yurtseven ME, Kaplan S: Pinealectomy exaggerates and melatonin treatment suppresses neuroma formation of transected sciatic nerve in rats: gross morphological, histological and stereological analysis. J Pineal Res, 38 (4): 284-291, 2005.
13. Brigaga MRPL, Barroso AS, Colepicolo P: Fluctuation of reactive oxygen species released by inflammatory cells. In, Vanden Driessche T, Guisset J-L, Petiau-de Vries G (Eds): The Redox State and Circadian Rhythms. 1st ed., pp. 177-191, Kluwer Academic Publishers, The Netherlands, 2000.
14. Hodoğlugil U, Ongun O, Güney Z, Altan N, Zengil H: Temporal variation in hepatic superoxide dismutase activity in mice. Chronobiol Int, 12 (2): 152-155, 1995.
15. Reiter RJ: Interactions of the pineal hormone melatonin with oxygen- centered free radicals: A brief review. Braz J Med Biol Res, 26 (11): 1141-1155, 1993.
16. Guney Y, Hicsonmez A, Uluoglu C, Guney HZ, Ozel Turkcu U, Take G, Yucel B, Caglar G, Bilgihan A, Erdogan D, Nalca Andrieu M, Kurtman C, Zengil H: Melatonin prevents inflammation and oxidative stress caused by abdominopelvic and total body irradiation of rat small Intestine. Braz J Med Biol Res, 40 (10): 1305-1314, 2007.
17. Guney Y, Uluoglu C, Hicsonmez A, Ozel Turkcu U, Ozbey G, Bilgihan A, Nalca Andrieu M, Guney HZ, Zengil H: Day and night effect of single dose of ionising radiation and melationin treatment of lung tissue of rats. Turk J Biochem, 33 (3): 104-110, 2008.
18. Take G, Erdogan D, Helvacioglu F, Göktas G, Ozbey G, Uluoglu C, Yücel B, Guney Y, Hicsonmez A, Ozkan S: Effect of melatonin and time of administration on irradiation-induced damage to rat testes. Braz J Med Biol Res, 42 (7): 621-628, 2009.
19. Steel RGD, Torrie JH, Dickey DA: Principles and Procedures of Statistics: A Biometrical Approach. 3rd ed., New York: Mc Graw-Hill, New York, 1997.
20. Popichiev VV, Yakovleva ND, Konoplyannikov AG, Kıvetnoi IM, Kita K, Kita I: Ultrastructure of pineal gland after γ-irradiation under conditions of inhibitions of adrenocortical function. Bull Exp Biol Med, 135, 706-710, 2002.
21. Reiter RJ, Tan DX, Osuna C, Gitto E: Actions of melatonin in the reduction of oxidative stress: A review. J Biomed Sci, 7 (6): 444-458, 2000.
22. Vijayalaxmi, Reiter RJ, Tan DX, Herman TS, Thomas CR: Melatonin as a radioprotective agent: A review. Int J Radiat Oncol Biol Phys, 59 (3): 639- 653, 2004.
23. Luchetti F, Canonico B, Curci R, Battistelli M, Mannello F, Papa S, Tarzia G, Falcieri E: Melatonin prevents apoptosis induced by UV-B treatment in U937cell line. J Pineal Res, 40, 158-167, 2006.
24. Khavinson VKH, Yakovleva ND, Popuchiev VV, Kvetnoi IM, Manokhina RP: Reparative effect of epithalon on pineal gland ultrastructure in irradiated rats. Bull Exp Biol Med, 131, 98-103, 2001.
25. Haus E, Touitou Y: Principles of clinical chronobiology. In, Touitou Y, Haus E (Eds): Biologic Rhythms in Clinical and Laboratory Medicine. 2nd ed., pp. 6-34, Springer-Verlag, Berlin, 1994.
26. Haus E: Chronobiology of the mammalian response to ionizing radiation potential applications in oncology. Chronobiol Int, 19 (1): 77-100, 2002.
27. Scheving LE: Circadian rhythms in cell proliferation: their importance when investigating the basic mechanism of normal versus abnormal growth. Prog Clin Biol Res, 59, 39-79, 1981.
28. Haus E, Halberg F, Loken MK, Kim YS: Space radiation biology and related topics. In, Tobias CS, Todd P (Eds): Circadian Rhythmometry of Mammalian Radiosensitivity. 1st ed., pp. 435-474, Academic Press, New York, 1974.
29. Pizzarello DJ, Usaak D, Chua KE, Rhyne AL: Circadian rhythmicity in the sensitivity of two strains of mice to whole-body radiation. Science, 17 (145): 286-291, 1964.
30. Erdogan A, İpekçioğlu E: Radyo frekans sinyalinin rat spinal ganglion hücrelerinde kalsiyum bağımlı klor kanallarına etkisi. Kafkas Univ Vet Fak Derg, 15 (5): 739-744, 2009.