SIÇAN PREFRONTAL KORTEKSİNDE FORMALDEHİT MARUZİYETİYLE OLUŞAN OKSİDATİF HASARA KARŞI MELATONİN HORMONUNUN KORUYUCU ETKİSİ

Year 2004, Volume: 13 Issue: 2, 1 - 7, 01.09.2004

İlter Kuş İsmail Zararsız H.ramazan Yılmaz Aslı Özdem Türkoğlu Hıdır Pekmez Mustafa Sarsılmaz

Abstract

Bu çalışmada, formaldehitin prefrontal korteks üzerine olan nörotoksik etkileri ve bu toksik etkilere karşı melatonin hormonunun koruyucu etkisi biyokimyasal düzeyde araştırıldı. Bu amaçla, 21 adet Wistar-Albino cinsi erkek sıçan üç gruba ayrıldı. Grup I’deki sıçanlar kontrol olarak kullanıldı. Grup II’deki sıçanlara gün aşırı % 10’luk formaldehit intraperitoneal olarak enjekte edildi. Grup III’deki sıçanlara ise, formaldehit enjeksiyonu ile birlikte günlük olarak 25 mg/kg dozunda melatonin uygulandı. Ondört günlük deney süresi sonunda bütün sıçanlar dekapitasyon yöntemi ile öldürüldü. Daha sonra sıçanların beyinleri çıkartılarak, prefrontal korteks örneklerinde süperoksit dismutaz (SOD), glutatyon peroksidaz (GSH-Px) ve malondialdehit (MDA) enzim aktiviteleri spektrofotometrik olarak belirlendi. Formaldehit uygulanan sıçanlarda SOD ve GSH-Px değerlerinin kontrol grubuna göre anlamlı bir şekilde azaldığı, MDA düzeylerinin ise yine istatistiksel olarak anlamlı bir şekilde arttığı tespit edildi. Formaldehit maruziyeti ile birlikte melatonin enjekte edilen sıçanlarda, SOD ve GSH-Px enzim aktivitelerinde bir artış olurken, MDA değerlerinde istatistiksel olarak anlamlı bir düşüş olduğu görüldü. Sıçanlarda, formaldehit maruziyeti sonucu prefrontal kortekste oksidatif hasarın oluştuğu ve bu hasarın melatonin uygulaması ile önlendiği tespit edildi

Keywords

Formaldehit, melatonin, süperoksit dismutaz, glutatyon peroksidaz, malondialdehit

The Protective Effects of Melatonin Hormone Against Exposure of Formaldehyde-Induced Oxidative Damage in Prefrontal Cortex of Rats

Abstract

In this study, neurotoxic effects of formaldehyde on prefrontal cortex and protective effects of melatonin hormone against these toxic effects were investigated at biochemical level. For this purpose, 21 adult male Wistar rats were divided into three groups. Rats in group I were used as control. Rats in group II were injected every other day with 10 % formaldehyde. Rats in group III were daily administered melatonin with (25 mg/kg) injection of formaldehyde. At the end of fourteen-days experimental period, all rats were killed by decapitation. Then the brains of rats were removed. The activites of superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and malondialdehyde (MDA) were determined in the prefrontal cortex specimens by using spectrophotometric methods. The levels of SOD and GSH-Px were significantly decreased, and MDA levels were significantly increased in rats treated with formaldehyde compared to control. It was seen that increase of SOD and GSH-Px enzyme activities, and decrease of MDA levels in rats administered melatonin with exposure of formaldehyde. It was determined that exposure of formaldehyde caused oxidative damage in prefrontal cortex of rats and this damage was prevented by administration of melatonin

Keywords

Formaldehyde, melatonin, superoxide dismutase, glutathione peroxidase, malondialdehyde

References

• Arıncı K, Elhan A. Anatomi (2.cilt). Güneş Kitabevi, Ankara 1995, ss: 388.
• Duncan J. An adaptive coding model of neural function in prefrontal cortex. Nat Rev Neurosci 2001, 2: 820-829.
• Nyberg L, Marklund P, Persson J, et al. Common prefrontal activations during working memory, episodic memory, and semantic memory. Neuropsychologia 2003, : 371-377.
• Ganong WF. Tıbbi fizyoloji. Nobel Tıp Kitabevi, İstanbul 2002, ss: 249-268.
• Ranganath C, Johnson MK, D’Esposito M. Prefrontal activity associated with working memory and episodic long-term memory. Neuropsychologia 2003, 41: 378-389.
• Smith AE. Formaldehyde. Occup Med 1992, : 83-88.
• Usanmaz SE, Akarsu ES, Vural N. Neurotoxic effects of acute and subacute formaldehyde exposures in mice. Envir Toxicol Pharmacol , 11: 93-100. Kilburn KH, Warshaw R, Thornton JC. Formaldehyde impairs memory, equilibrium, and dexterity in histology technicians: effects which persist for days after exposure. Arch Environ Health 1987, 42: 117-120.
• Kilburn KH. Neurobehavioral impairment and seizures from formaldehyde. Arch Environ Health 1994, 49: 37- 44.
• Stroup NE, Blair A, Erikson GE. Brain cancer and other causes of deaths in anatomists. J Natl Cancer Inst 1986, 77: 1217-1224.
• Pitten FA, Kramer A, Herrmann K, Bremer J, Koch S. Formaldehyde neurotoxicity in animal experiments. Pathol Res Pract 2000, : 193-198.
• Arendt J. Melatonin. Clin Endocrinol 1988, : 205-209.
• Kuş İ, Sarsılmaz M. Pineal bezin morfolojik yapısı ve fonksiyonları. T Klin J Med Sci , 22: 221-226. Forsling ML, Stoughton RP, Zhou Y, Kelestimur H, Demaine C. The role of the pineal in the control of the daily patterns of neurohypophysial hormone secretion. J Pineal Res 1993, 14: 45-51.
• Kus I, Akpolat N, Ozen OA, Songur A, Kavakli A, Sarsilmaz M. Effects of melatonin on Leydig cells in pinealectomized rat: an immunohistochemical study. Acta Histochem , 104: 93-97. Guerrero JM, Reiter RJ. A brief survey of pineal gland-immune system interrelationships. Endocr Res 1992, 18: 91
• Ayar A, Kutlu S, Yilmaz B, Kelestimur H. Melatonin inhibits spontaneous and oxytocin- induced contractions of rat myometrium in vitro. Neuroendocrinol Lett 2001, 22: 301
• Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterisation of erythrocyte glutathione peroxidase. J Lab Clin Med 1967, 70: 158
• Esterbauer H, Cheeseman KH. Determination of aldehydic lipid peroxidation products: malonaldehyde and hidroxynonenal. Methods Enzymol 1990, : 407-421.
• Kim H, Kim YD, Cho SH. Formaldehyde exposure levels and serum antibodies to formaldehyde- human serum albumin of Korean medical students. Arch Environ Health 1999, 54: 115-118.
• Sarsılmaz M, Özen OA. Subkronik dönem boyunca formaldehit soluyan sıçanların leydig hücrelerindeki histopatolojik değişiklikler. Fırat Tıp Dergisi 2000, 2: 1-5.
• Nilsson JA, Zheng X, Sundqvist K, et al. Toxicity of formaldehyde to human oral fibroblasts and epithelial cells: influences of culture conditions and role of thiol status. J Dent Res 1998, 77: 1896-1903.
• Thrasher JD, Kilburn KH. Embryo toxicity and teratogenicity of formaldehyde. Arch Environ Health 2001, 56: 300-311.
• Kuo H, Jian G, Chen C, Liu C, Lai J. White blood cell count as an indicator of formaldehyde exposure. Bull Environ Contam Toxicol 1997, 59: 261-267.
• Akyol Ö. Beyin tümörlerinde doku SOD, CAT ve GSH-Px aktiviteleri. Uzmanlık tezi, Ankara Üni. Tıp Fakültesi Biyokimya Anabilim Dalı, Ankara 1994, ss: 12-18.
• Teng S, Beard K, Pourahmad J, et al. The formaldehyde metabolic detoxification enzyme systems and molecular cytotoxic mechanism in isolated rat hepatocytes. Chem Biol Interact 2001, 130-132: 285- Clin Chem 1988, 34: 497-500.
• Mason RP, Leeds PR, Jacob RF, et al. Inhibition of excessive neuronal apoptosis by the calcium antagonist amlodipine and antioxidants in cerebellar granule cells. J Neurochem 1999, 72: 1448-1456.
• Kaptanoğlu E, Palaoglu S, Demirpence E, Akbiyik F, Solaroglu I, Kilinc A. Different responsiveness of central nervous system tissues to oxidative conditions and to the antioxidant effect of melatonin. J Pineal Res 2003, 34: 32-35.
• Erol FS, Topsakal C, Ozveren MF, et al. Protective effects of melatonin and vitamin E in brain damage due to gamma radiation: an experimental study. Neurosurg Rev , 27: 65-69.