MELATONİN VE C VİTAMİNİ’NİN KRONİK ALKOLİK SIÇANLARIN AKCİĞER DOKUSUNDAKİ HASAR VE eNOS İMMUNREAKTİVİTESİ ÜZERİNE ETKİLERİ

Öz

Bu çalışmada alkolün akciğerde oluşturduğu hasar ve endotelyal nitrik oksit sentaz ekspresyonu üzerine melatonin ve C vitamininin koruyucu etkilerinin belirlenmesi amaçlandı.Çalışmada 24 adet 200-250 gr ağırlığında Wistar cinsi ergin erkek sıçan kullanıldı. Sıçanlar rasgele olarak dört gruba ayrıldı. Birinci grup kontrol (n:6); ikinci grup deney süresince (28 gün) sadece alkol içeren sıvı diyet alan (n:6); üçüncü grup deney boyunca alkol içeren sıvı diyet ile birlikte 40mg/kg/gün intraperitoneal C vitamini alan (n:6); dördüncü grup deney süresince alkol içeren sıvı diyet ile birlikte 4mg/kg/gün intraperitoneal melatonin alan sıçanlardan (n:6) oluşturuldu.Deney süresince sadece alkol alan gruptaki sıçanların akciğer dokularında alveolar septumda kalınlaşma ve bazı bronşiol epitel hücrelerinde dökülme gözlendi. Bazı alanlarda alveolar ödem ve hemoraji tespit edildi. Endotelyal nitrik oksit sentaz immunoreaktivitesini belirlemek için yapılan boyamada bronşiol epitel hücrelerinde (+++), alveolar septumda (++) ve bronşiol ve damarların düz kaslarında ise (+) boyanma tespit edildi. Alkol tüketen grupta bronşiol epitelindeki boyanmada önemli miktarda azalma gözlendi. Melatonin ve C vitamini gruplarında ise endotelyal nitrik oksit sentaz boyanması kontrol grubuna benzerlik göstermekteydi ve oluşan morfolojik hasarlar düzelmişti. Sonuç olarak kronik alkol tüketimi akciğer dokusunda hasara yol açmaktadır. Bu hasar melatonin ve C vitamini ile düzelmektedir

Anahtar Kelimeler

• Kronik alkol tüketimi, akciğer, eNOS, melatonin, C vitamini

Effect of Melatonin and Vitamin C on Damage and Expression of Endothelial NOS in Lung of Chronic Alcoholic Rats

Öz

The aim of this study was to determine the expression of endothelial nitric oxide synthase and alterations in the lung caused by alcohol consumption and the effects of melatonin and vitamin C on these changes in rats.Twenty-four adult male Wistar rats weighing 200-250g were used in this study. Rats were divided into four groups. The first group served as control (n:6). The second group was the ethanol treatment for 28 days (n:6). The third group was given ethanol and supplemented with 40 mg/kg/day vitamin C (intraperitoneally) (n:6). The fourth group was given ethanol and supplemented with 4 mg/kg/day melatonin (intraperitoneally) (n:6). Light microscopic examinations revealed thickening in alveolar septum and desquamation of some bronchial epithelial cells in the ethanol-fed group. In some fields, alveolar observed.immunoreactivity was in (+++) bronchial epithelial cells, (++) in alveolar septum and (+) in smooth muscle of bronchioli and vessels. Expression of endothelial nitric oxide synthase in alcohol group was decreased comparedto control group. In melatonin and vitamin C treated groups, immunoreactivity resembled that of control group, and morphological damage was partly improved.Our finding have led us to conclude that chronic alcohol consumption results in damage to pulmonary tissue, which can only be resolved with especially melatonin and vitamin C

Anahtar Kelimeler

• Chronic alcohol consumption, lung, eNOS, melatonin, Vitamin C

Kaynakça

1. Cuesta MA, et al. Distribution of nitric oxide synthase in normal and cirrhotic human liver. Proc Natl Acad Sci USA 2002; 99(26):17161- 6.
2. Borniquel S, Valle I, Cadenas S, Lamas S, Monsalve M. Nitric oxide regulates mitochon- drial oxidative stres protection via the tran- scriptional coactivator PGC-1 alpha. FASEB J 2006; 20(11):1889-91.
3. Naidu KA. Vitamin C in human health and disease is still a mystery ? An overview. Nutr J 2003; 2:7.
4. Wintergerst ES, Maggini S, Hornig DH. Im- mune-enhancing role of vitamin C and zinc and effect on clinical conditions. Ann Nutr Metab 2006; 50(2):85-94.
5. Kojo S. Vitamin C: basic metabolism and its function as an index of oxidative stress. Curr Med Chem 2004; 11(8):1041-64.
6. Bhatia AL, Manda K. Study on pre-treatment of melatonin against radiation- induced oxidative stres in mice. Env Tox and Phar 2004; 18: 13-20.
7. Uzbay IT, Kayaalp SO. A modified liquid diet of chronic ethanol administration: validation by ethanol withdrawal syndrome in rats. Pharmacol Res 1995; 31:37–42.
8. Louis ED, Yi H, Erickson-Davis C, Vonsattel JP, Faust PL. Structural study of Purkinje cell axonal torpedoes in essential tremorNeurosci Lett. 2009;450(3):287-91

9. Sonmez MF, Colakoglu N, Kukner A, Ozan E, Dabak DO. Immunolocalization of TGF-beta2 in the rat thymus during late stages of prenatal development. Acta Histochem. 2009;111(1):68-73.
10. Brown LA, Harris FL, Ping XD, Gauthier TW. Chronic ethanol ingestion and the risk of acute lung injury: a role for glutathione availability? Alcohol 2004; 33(3):191-7.
11. Brown LA, Harris FL, Bechara R, Guidot DM. Effect of chronic ethanol ingestion on alveolar type II cell: glutathione and inflammatory mediator-induced apoptosis. Alcohol Clin Exp Res 2001; 25:1078–1085.
12. Brown LA, Harris FL, Guidot DM. Chronic ethanol ingestion potentiates TNF-alpha- mediated oxidative stress and apoptosis in rat type II cells. Am. J Physiol Lung Cell Mol Physiol 2001; 281:377–386.
13. Guidot DM, Brown LA. Mitochondrial glutathione replacement restores surfactant synthesis and secretion in alveolar epithelial cells of ethanol-fed rats. Alcohol Clin Exp Res 2000; 24:1070–1076.
14. Guidot DM, Hart CM. Alcohol abuse and acute lung injury: epidemiology and pathophysiology of a recently recognized association. J Investig Med 2005; 53:235– 245.
15. Polikandriotis JA, Rupnow HL, Elms SC, et al. Chronic superoxide production and NADPH oxidase expression in the lung. Am J Respir Cell Mol Biol 2006; 34:314–319. increases
16. Brown LA, Cook RT, Jerrells TR, et al. Acute and chronic alcohol abuse modulate immunity. Alcohol Clin Exp Res 2006; 30 (9):1624-31.
17. Moriya N, Nihira M, Sato S, Watanabe T. Ultrastructural changes of liver, heart, lung and kidney of mice in a large dose of ethanol injection. Arukoru Kenkyuto Yakubutsu Ison 1992; 27(2):189-200.
18. Venizelos PC, Gerrity TR, Yeates DB. Response of human mucociliary clearance to acute alcohol administration. Arch Environ Health 1981; 36:194–201.
19. Heinemann HO. Alcohol and the lung. A brief review Am J Med 1977; 63:81–85.
20. Asano K, Chen BCE, Gaston B, et al. Constitutive and inducible nitric oxide synthase gene expression regulation and activity in human lung epithelial cells. Proc Natl Acad Sci USA 1994; 71:10089.
21. Shad PW, North AJ, Wu LC, et al. Endothelial nitric oxide synthase is expressed in cultured human bronchiolar epithelium. J Clin Invest 1994; 94:2231.
22. Xue C, Botkin SJ, Johns RA. Localization of endothelial NOS at the basal microtubule membrane in ciliated epithelium of rat lung. J Histochem Cytochem 1996; 44(5):463-71.
23. Tamaoki J, Chiyotani A, Kondo M, Konno K. The role of NO generation in B-adrenoceptor in mediated stimulation of rabbit airway ciliary motility. Am J Physiol 1995; 268:1342.
24. Cox RA, Jacob S, Oliveras G, et al. Pulmonary expression of nitric oxide synthase isoforms in sheep with smoke inhalation and burn injury. Exp Lung Res 2009; 35(2):104- 18.
25. Polikandriotis JA, Rupnow HL, Hart CM. Chronic endothelial cell nitric oxide production through PI-3 kinase- and hsp90-dependent mechanisms. Alcohol Clin Exp Res 2005; 29:1932–1938. stimulates
26. Lindberg S, Cervin A, Runer T. Low levels of nasal nitric oxide (NO) correlate to impaired mucociliary function in the upper airways. Acta Otolaryngol 1997; 117:728–734.
27. Şener G, Şehirli AÖ, Şatıroğlu H, Uysal MK, Yeğen BÇ. Melatonin prevents oxidative kidney damage in a rat model of thermal injury. Life Sci 2002; 2977-2985.
28. Serin M, Gülbaş H, Gürses I, Erkal HS, Yücel N. The histopathological evaluation of the effectiveness of melatonin as a protectant against acute lung injury induced by radiation therapy in a rat model. Int J Radiat Biol 2007; 83(3):187-93.
29. Pignone AM, Rosso AD, Fiori G, et al. Mela- tonin is a safe and effective treatment for chronic pulmonary and extrapulmonary sarcoidosis. J Pineal Res 2006; 41(2):95-100.