Gebelikte Tütün Dumanı Maruziyetinin Anne Sıçan Akciğer Dokusunda Meydana Getirdiği Değişiklikler Üzerine Alfa Lipoik Asitin Etkilerinin İncelenmesi

Yıl 2018, , 297 - 307, 05.09.2018

Elif Erdem Güzel , Nalan Kaya Gonca Ozan Kocamüftüoğlu Mehmet Ali Kısaçam Dürrin Özlem Dabak İbrahim Enver Ozan

https://doi.org/10.5798/dicletip.457249

Öz

Amaç: Çalışmamızda gebelikte tütün dumanına maruz
kalan anne sıçanların akciğer dokusunda meydana gelen değişiklikler üzerine
alfa lipoik asitin etkilerinin deneysel sıçan modeli üzerinde araştırılması
amaçlandı.

Yöntemler: Çalışmada 28 adet dişi Sprague-Dawley cinsi
sıçanlar kullanıldı. Gebe sıçanlar; Kontrol grubu, Tütün dumanı (TD) grubu,
Tütün dumanı + Alfa lipoik asit (TD+ALA) grubu ve Alfa lipoik asit (ALA) grubu
olmak üzere rastgele dört eşit gruba ayrıldı. TD ve TD+ALA grubundaki sıçanlar
çiftleşmeden önce sekiz hafta ve gebelik süresince günde iki saat tütün
dumanına maruz bırakıldı.

TD+ALA ve ALA grubundaki sıçanlara ise çiftleşmeden
önce sekiz hafta ve gebelik süresince gün aşırı oral gavaj yolu ile 20 mg/kg
dozunda alfa lipoik asit verildi. Deneyin sonunda sıçanlar dekapite edilerek
akciğer dokuları çıkarıldı ve histolojik, biyokimyasal ve immünohistokimyasal
metotlar uygulandı.

Bulgular: TD grubuna ait akciğer kesitlerinde
inflamatuar hücre artışı, konjesyon, ödem, hemoraji gibi histopatolojik
bulgular gözlendi. ALA uygulamasıyla bu histopatalojik bulgularda istatistiksel
olarak anlamlı oranda düzelmeler izlendi. TD grubunda VEGF immünreaktivitesinin
kontrol grubuna göre anlamlı artış gösterdiği, TD+ALA grubunda ise TD grubuna
göre VEGF immünreaktivitesinin anlamlı derecede azaldığı belirlendi. TD
grubunda MDA değerlerinin kontrole göre anlamlı derecede arttığı, TD+ALA
grubunda ise TD grubuna göre anlamlı derecede azaldığı gözlendi.

Sonuç: Tütün dumanının gebe sıçan akciğerinde yol
açtığı oksidatif hasarın, alfa lipoik asit tedavisinin antioksidan etkileri ile
kısmen engellendiği belirlendi. 

Anahtar Kelimeler

Gebelik, tütün dumanı, alfa lipoik asit, akciğer

Kaynakça

• 1. World Health Organization. Tobacco Free Initiative. Protection from exposure to second-hand tobacco smoke. Policy recommendations. http://www.who.int/ tobacco/en/ (Erişim tarihi: 05.02.2018).
• 2. Environmental Tobacco Smoke Air Quality Guidelines - Second Edition WHO Regional Office for Europe, Copenhagen, Denmark, 2000. http://www.euro. who.int/document/aiq/8_1ets.pdf (Erişim Tarihi:05.02.1018).
• 3. Besaratinia A, Pfeifer GP. Second-hand smoke and human lung cancer. Lancet Oncol 2008;9:657-63.
• 4. Glantz SA, Parmley WW. Passive smoking and heart disease. Epidemiology, physiology, and biochemistry. Circulation 991;83:1-12.
• 5. Türkiye Halk Sağlığı Kurumu. Küresel Yetişkin Tütün Araştırması Türkiye. Ankara: Anıl Matbaa, 2014.
• 6. WHO recommendations for the prevention and management of tobacco use and second-hand smoke exposure in pregnancy. World Health Statistics, 2013.
• 7. Küresel Yetişkin Tütün Araştırması Türkiye –T.C. Sağlık Bakanlığı Türkiye Halk Sağlığı Kurumu. Ankara 2012. 8. Nakamura MU, Alexandre SM, Kuhn dos Santos JF, et al. Obstetric and perinatal effects of active and/or passive smoking during pregnancy. Sao Paulo Med J 2004;122:94-8.
• 9. U.S. Department of Health and Human Services. The Health Consequences of Smoking: A Report of the Surgeon General. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. 2004.
• 10. Le Cras TD, Spitzmiller RE, Albertine KH, et al. VEGF causes pulmonary hemorrhage, hemosiderosis, and air space enlargement in neonatal mice. Am J Physiol Lung Cell Mol Physiol 2004;287:134–42.
• 11. Lee KS, Park HS, Park SJ, et al. A prodrug of cysteine, L-2-oxothiazolidine-4-carboxylic acid, regulates vascular permeability by reducing vascular endothelial growth factor expression in asthma. Mol Pharmacol 2005;68:1281–90.
• 12. Goraca A, Huk-Kolega H, Piechota A. Lipoic acidbiological activity and therapeutic potential. Pharmacol Rep 2011;63:849–58.
• 13. Al Ghafli MHM, Padmanabhan R, Kataya HH, et al. Effects of α-lipoic acid supplementation on maternal diabetes-induced growth retardation and congenital anomalies in rat foetuses. Mol cell Biochem 2004;1–13.
• 14. Kılıç A, Uyanıkoğlu H, İncebıyık A. Rat Overinde İskemi-Reperfüzyon Üzerine N-Asetil Sistein ve Resveratrol’ün Koruyucu Etkisi. Dicle Med J 2016;43:229-36.
• 15. Balgetir F, Kocaman N. Deneysel Diyabetik Ratların Beyin Dokusunda İrisin İmmünreaktivitesi Üzerine Losartanın Etkileri. Fırat Tıp Derg 2016;21:63-6.
• 16. Placer ZA, Cushmann LL, Johnson BC. Estimation of products of lipid peroxidation (as malondialdehyde) in biochemical systems. Analytical Biochemistry1966;16:359-64.
• 17. Mori Y, Limura K, Furukawa F, et al. Effect of cigarette smoke on the mutagenic activation of various carcinogens in hamsters. Mutat Res 1995;346:1–8.
• 18. De Marini DM, Shelton ML, Levine JG. Mutation spectrum of cigarette smoke condensate in Salmonella: comparison to mutation in smoking-associated tumors. Carcinogenesis 1995;16:2535–42.
• 19. Gupta S, Agarwal A, Banerjee J, et al. The role of oxidative stress in spontaneous abortion and recurrent pregnancy loss: a systematic review. Obstet Gynecol Surv 2007;62:335-47.
• 20. Burton GJ, Jauniaux E. Placental oxidative stress: from miscarriage to preeclapmsia. J Soc Gynecol Investig 2004;11:342-52.
• 21. Ziad S, Wajdy A, Darwish B. Effects of cigarette smoking on histology of trachea and lungs of albino rat. Res Opin Anim Vet Sci 2013;3:356-62.
• 22. Lobo V, Patil A, Phatak A, et al. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn Rev 2010;4:118-26.
• 23. Dogan OM, Elagoz S, Ozsahin SF, et al. Pulmonary toxicity of chronic exposure to tobacco and biomass smoke in rats. Clinics 2011;66:1081-87.
• 24. Abbott LC, Winzer-Serhan UH. Smoking during pregnancy: lessons learned from epidemiological studies and experimental studies using animal models. Critical Reviews in Toxicology 2012;42:279–303.
• 25. Czekaj P, Pałasz A, Lebda-Wyborny T. Morphological changes in lungs, placenta, liver and kidneys of pregnant rats exposed to cigarette smoke. Int Arch Occup Environ Health 2002;75:27-35.
• 26. Kusterer K, Blochle C, Konrad T, et al. Rat liver injury induced by hypoxic ischemia and reperfusion: protective action by somatostatin and two derivatives. Regul Pept 1993;44:251–6.
• 27. Wright JL, Tai H, Dai J, et al. Cigarette smoke induces rapid changes in gene expression in pulmonary arteries. Lab Invest 2002;82:1391-8.
• 28. Wright JL, Churg A. Effect of long-term cigarette smoke exposure on pulmonary vascular structure and function in the guinea pig. Exp Lung Res 1991;17:9971009.
• 29. Christou H, Yoshida A, Arthur V, et al. Increased vascular endothelial growth factor production in the lungs of rats with hypoxia-induced pulmonary hypertension. Am J Respir Cell Mol Biol 1998;18:768– 76.
• 30. Rovina N, Papapetropoulos A, Kollintza A, et al. Vascular endothelial growth factor: an angiogenic factor reflecting airway inflammation in healthy smokers and in patients with bronchitis type of chronic obstructive pulmonary disease? Respir Res 2007;8:53.
• 31. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000;407:249–57.
• 32. Kunig AM, Balasubramaniam V, Markham NE, et al. Recombinant human VEGF treatment tran siently increases lung edema but enhances lung structure after neonatal hyperoxia. Am J Physiol Lung Cell Mol Physiol 2006;291:1068–78.
• 33. Aldini G, Dalle-Donne I, Colombo R, et al. Lipoxidation-derived reactive carbonyl species as potential drug targets in preventing protein carbonylation and related cellular dysfunction. Chem Med Chem 2006;1:1045–58.
• 34. Nadiger HA, Mathew CA, Sadasivudu B. Serum malondialdehyde (TBA reactive substance) levels in cigarette smokers. Atherosclerosis 1987;64:71-3.
• 35. Moretto N, Facchinetti F, Southworth T, et al. alpha, beta-Unsaturated aldehydes contained in cigarette smoke elicit IL-8 release in pulmonary cells through mitogen-activated protein kinases. Am J Physiol Lung Cell Mol Physiol 2009;296:839–48.
• 36. Edirisinghe I, Yang SR, Yao H, et al. VEGFR-2 inhibition augments cigarette smoke-induced oxidative stress and inflammatory responses leading to endothelial dysfunction. Faseb J 2008;22:2297–310.
• 37. Duthie GG, Arthur JR, James WP. Effects of smoking and vitamin E on blood antioxidant status. Am J Clin Nutr 1991;53:1061–3.
• 38. Fotsis T, Pepper MS, Aktas E, et al. Flavonoids, dietary-derived inhibitors of cell proliferation and in vitro angiogenesis. Cancer Res 1997;57:2916-21.
• 39. Oak MH, El Bedoui J, Schini-Kerth VB. Antiangiogenic properties of natural polyphenols from red wine and green tea. J Nutr Biochem 2005;16:1-8.
• 40. Savitha S, Tamilselvan J, Anusuyadevi M, et al. Oxidative stress on mitochondrial antioxidant defense system in the aging process: Role of DL-ɑ-lipoic acid and L-carnitine. Clin Chim Acta 2005;355:173-80.
• 41. Schwartz L, Guais A, Israel M, et al. Tumor regression with a combination of drugs interfering with the tumor metabolism: efficacy of hydroxycitrate, lipoic acid and capsaicin. Invest New Drugs 2013;31: 256–64.
• 42. Mantovani G, Maccio A, Melis G, et al. Restoration of functional defects in peripheral blood mononuclear cells isolated from cancer patients by thiol antioxidant alpha-lipoic acid and N-acetyl cysteine. Int J Cancer 2000;86:842–7.