Effects of N-acetylcysteine on the lung histopathology and oxidant-antioxidant status in rabbits exposed to cigarette smoke

Bu çalışmamızda sigara dumanının akciğer histopatolojisi ve oksidan-antioksidan sistem üzerine etkilerini ve N-asetilsisteinin (NAC) oluşan bu değişiklikler üzerine etkisini değerlendirmeyi amaçladık. Bu amaçla bir grup tavşan cam bir kafes içinde bir ay boyunca günde bir saat sigara dumanına maruz bırakıldı. Bir grup tavşana sadece intraperitoneal NAC enjekte edildi. Bir grup tavşan hem sigara dumanına maruz bırakıldı hem de intraperitoneal NAC enjekte edildi. Kontrol grubu tavşanlara ise cam kafes içinde temiz hava verildi. Bir ayın sonunda hayvanlar sakrifiye edilerek akciğer dokuları histopatolojik olarak incelendi. Ayrıca, kan örneklerinde protein sülfhidrilleri, karboniller, prostaglandin F2α (PGF2α) ve malondialdehid (MDA) düzeyleri ölçüldü. Sigara grubunda intraparankimal vasküler konjesyon ve tromboz, intraparankimal hemoraji, respiratuar epitel proliferasyonu, alveoler ve bronşiyoler lümenlerdeki makrofajların sayısı, alveoler destrüksiyon, amfizematöz değişiklikler ve bronkoalveoler hemoraji skorları kontrol grubuna göre anlamlı olarak artmış olarak bulundu. Sigara grubu tavşanların kanında kontrol grubuna göre protein sülfhidrilleri anlamlı azalmış, karboniller, PGF2α ve MDA düzeyleri anlamlı olarak artmış bulundu. Sigara dumanına maruz bırakılan tavşanlara NAC verilmesinin sadece bronkoalveoler hemoraji skorunda ve kan PGF2α düzeylerinde anlamlı azalmaya neden olduğu görüldü. Diğer parametrelerde değişiklik saptanmadı. Sonuç olarak sigara dumanına maruziyet tavşan akciğerlerinde ciddi histopatolojik değişiklikler oluşturmakta ve oksidan-antioksidan sistemi negatif etkilemektedir. Günlük düşük doz NAC verilmesinin sigara dumanına bağlı gelişen histopatolojik değişiklikler ve oksidan-antioksidan sisteme sınırlı yararlı etkileri vardır.

N-asetilsisteinin sigara dumanına maruz bırakılan tavşanlarda akciğer histopatolojisi ve oksidan-antioksidan sistem üzerine etkileri

We aimed to evaluate the effects of smoking on the histopathology and the oxidant-antioxidant status of lungs and to test the effects of N-acetylcysteine (NAC) on the induced changes. Rabbits were exposed to cigarette smoke (CS) in a glass chamber for one hour daily for one month. An NAC control group was given intraperitoneal NAC only. CS + NAC rats were exposed to smoke and given intraperitoneal NAC. A control group was exposed to clean air only. At the end of one month, animals were sacrificed and lung tissues were examined histopathologically. Blood levels of protein sulfhydryls, carbonyls, prostaglandin F2α (PGF2α) and malondialdehyde (MDA) were measured. Intraparenchymal vascular congestion and thrombosis, intraparenchymal hemorrhage, respiratory epithelial proliferation, number of macrophages in the alveolar and bronchial lumen, alveolar destruction, emphysematous changes and bronchoalveolar hemorrhage scores were significantly increased in rabbits exposed to CS compared with the control group. Protein sulfhydryls were significantly decreased; carbonyls, PGF2α and MDA levels were significantly increased in the smoke exposed rabbits. Administration of NAC to rabbits exposed to CS caused a reduction in the bronchoalveolar hemorrhage score and blood PGF2α levels. Other parameters were unaffected by NAC. Exposure to CS causes severe histopathological changes and negatively effects the oxidant-antioxidant status in the lungs of rabbits. A low daily dose of NAC has some ameliorative effects on histopathological changes and oxidant-antioxidant status of the lungs in smoke exposed rabbits.

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  • 1. Halliwell B. Oxidants and human disease: Some new concepts. FASEB J 1987; 1: 358-64.
  • 2. Rahman I, MacNee W. Role of oxidants/antioxidants in smoking induced lung diseases. Free Radic Biol Med 1996; 21: 669-81.
  • 3. Nakayama T, Church DF, Pryor WA. Quantitative analysis of the hydrogen peroxide formed in aqueous cigarette tar extracts. Free Radic Biol Med 1989; 7: 9-15.
  • 4. Rubio ML, Sanchez-Cifuentes MV, Ortega M, et al. Nacetylcysteine prevents cigarette smoke induced small airways alterations in rats. Eur Respir J 2000; 15: 505-11.
  • 5. Seagrave JC. Oxidative mechanisms in tobacco smokeinduced emphysema. J Toxicol Environ Health 2000; 61:69-78.
  • 6. Ventresca GP, Cicchetti V, Ferrari V. Acetylcysteine. In: Braga PC, Allegra L (eds). Drugs in Bronchial Mucology. New York: Raven Press, 1989: 77-102.
  • 7. Aruoma OI, Halliwell B, Hoey BM, Butler J. The antioxidant action of N-acetylcysteine: Its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. Free Radic Biol Med 1989; 6: 593-7.
  • 8. Gillissen A, Jaworska M, Orth M, et al. N-acystelyn, a novel lysine salt of N-acetylcysteine, to augment cellular antioxidant defence in vitro. Respir Med 1997; 91: 159-68.
  • 9. Phelps DT, Deneke SM, Daley DL, Fanburg BL. Elevation of glutathione levels in bovine pulmonary artery endothelial cells by N-acetylcysteine. Am J Respir Cell Mol Biol 1992; 7: 293-9.
  • 10. Fidan F, Unlu M, Sezer M, et al. Effects of environmental tobacco smoke and dried dung smoke on lung histopathology in rabbits. Pathology 2006; 38: 53-7
  • 11. Sciuto AM, Strickland PT, Kennedy TP, Gurtner GH. Protective effects of N-acetylcysteine treatment after phosgene exposure in rabbits. Am J Respir Crit Care Med 1995; 151: 768-72.
  • 12. Glantzounis GK, Yang W, Koti RS, et al. Continuous infusion of N-acetylcysteine reduces liver warm ischaemiareperfusion injury. Br J Surg 2004; 91: 1330-9.
  • 13. Jeremias A, Dusa C, Forudi F, et al. N-acetyl-cysteine in the prevention of vascular restenosis after percutaneous balloon angioplasty. Int J Cardiol 2004; 95: 255-60.
  • 14. Molteni A, Ward WF, Ts’ao CH, et al. Monocrotaline-induced pulmonary fibrosis in rats: Amelioration by captopril and penicillamine. Proc Soc Exp Biol Med 1985; 180: 112-20.
  • 15. Rotta AT, Gunnarsson B, Hernan LJ, et al. Partial liquid ventilation influences pulmonary histopathology in an animal model of acute lung injury. J Crit Care 1999; 14: 84-92.
  • 16. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxidase in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95: 351-8.
  • 17. Levine RL, Garland D, Oliver CN, et al. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 1990; 186: 464-78.
  • 18. Koster JF, Biemond P, Swaak AJ. Intracellular and extracellular sulfhydryl levels in rheumatoid arthritis. Ann Rheum Dis 1986; 45: 44-6.
  • 19. Church T, Pryor WA. Free radical chemistry of cigarette smoke and its toxicological implications. Environ Health Perspect 1985; 64: 111-26.
  • 20. Pryor WA. Cigarette smoke radicals and the role of free radicals in chemical carcinogenesis. Environ Health Perspect 1997; 105(Suppl 4): 875-82.
  • 21. Leanderson P, Tagesson C. Cigarette smoke-induced DNA damage in cultured human lung cells: Role of hydroxy radicals and endonuclease activation. Chem Biol Interact 1992; 81: 197-208.
  • 22. Cross CE, O’Neill CA, Reznick AZ, et al. Cigarette smoke oxidation of human plasma constituents. Ann NY Acad Sci 1993; 686: 72-89.
  • 23. Frei B, Forte TM, Ames BN, Cross CE. Gas phase oxidants of cigarette smoke induce lipid peroxidation and changes in lipoprotein properties in human blood plasma. Biochem J 1991; 277: 133-8.
  • 24. Reznick AZ, Cross CE, Hu ML, et al. Modification of plasma proteins by cigarette smoke as measured by protein carbonyl formation. Biochem J 1992; 286: 607-11.
  • 25. Sekhon HS, Wright JL, Churg A. Cigarette smoke causes rapid cell proliferation in small airways and associated pulmonary arteries. Am J Physiol 1994; 267: 557-63.
  • 26. Li T, Molteni A, Latkovich P, et al. Vitamin A depletion induced by cigarette smoke is associated with the development of emphysema in rats. J Nutr 2003; 133: 2629-34.
  • 27. Gokkusu C, Ademoglu E, Tamer S, Alkan G. Oxidant-antioxidant profiles of platelet rich plasma in smokers. Addict Biol 2001; 6: 325-30.
  • 28. Joshi UM, Kodavanti PR, Mehendale HM. Glutathione metabolism and utilization of external thiols by cigarette smoke-challenged, isolated rat and rabbit lungs. Toxicol Appl Pharmacol 1998; 96: 324-35.
  • 29. Eiserich JP, Van Der Vliet A, Handelman GJ, et al. Dietary antioxidants and cigarette smoke-induced biomolecular damage, a complex interaction. Am J Clin Nutr 1995; 62: 1490-500.
  • 30. Hong JL, Lee LY. Cigarette smoke-induced bronchoconstriction, causative agents and role of thromboxane receptors. J Appl Physiol 1996; 81: 2053-9.
  • 31. Bingol NK, Kacmaz M, Cimen YB, et al. Acute and chronic effects of smoking on blood antioxidant status. J Nutr Environ Med 1999; 9: 193-7.
  • 32. Unlu M, Ozguner MF, Sahin U, et al. Lipid peroxidation and changes of superoxide dismutase activity in the lung and blood induced by cigarette smoke exposure in rabbits. Biomed Res 2000; 11: 271-5.
  • 33. Neal R, Matthews RH, Lutz P, Ercal N. Antioxidant role of N-acetyl cysteine isomers following high dose irradiation. Free Radic Biol Med 2003; 34: 689-95.
  • 34. Fan J, Shek PN, Suntres ZE, et al. Liposomal antioxidants provide prolonged protection against acute respiratory distress syndrome. Surgery 2000; 128: 332-8.
  • 35. Cortijo J, Cerda-Nicolas M, Serrano A, et al. Attenuation by oral N-acetylcysteine of bleomycin-induced lung injury in rats. Eur Respir J 2001; 17: 1228-35.
  • 36. Shahzeidi S, Sarnstrand B, Jeffery PK, et al. Oral N-acetyl cysteine reduces bleomycin-induced collagen deposition in the lungs of mice. Eur Respir J 1991; 4: 845-52.
  • 37. Hagiwara SI, Ishii Y, Kitamura S. Aerosolized administration of N-acetylcysteine attenuates lung fibrosis induced by bleomycin in mice. Am J Respir Crit Care Med 2000; 162: 225-31.
  • 38. Behr J, Maier K, Degenkolb B, et al. Antioxidative and clinical effects of high-dose N-acetylcysteine in fibrosing alveolitis: Adjunctive therapy to maintenance immunosupression. Am J Respir Crit Care Med 1997; 156: 1897-901.
  • 39. Rogers DF, Jeffery PK. Inhibition by oral N-acetylcysteine of cigarette smoke-induced "bronchitis" in the rat. Exp Lung Res 1986; 10: 267-83.
  • 40. Balansky RB, D’Agostini F, Zanacchi P, De Flora S. Protection by N-acetylcysteine of the histopathological and cytogenetical damage produced by exposure of rats to cigarette smoke. Cancer Lett 1992; 64: 123-31.
Tüberküloz ve Toraks-Cover
  • ISSN: 0494-1373
  • Yayın Aralığı: 4
  • Başlangıç: 1951
  • Yayıncı: Tuba Yıldırım
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