Saliha Ayşenur ÇAM, Seyfullah Oktay ARSLAN

Kömür madeni ortamında tutulan sıçanlarda akciğer toksisitesinin in vivo solunum kayıtları ile değerlendirilmesi: Deneysel Bir Çalışma

Amaç: Maden işçileri çalışma ortamı koşullarında tozlara veya zehirli gazlara maruz kalmaktadır. Pnömokonyoz ve diğer akciğer hastalıkları, kömür tozu kaynaklı pulmoner toksisitenin reaktif oksijen türleriyle (ROS) ilişkili patogenezi ile karakterizedir. Yöntem: Bu çalışma, maden atmosferinde kömür tozu ve gazlarına maruz kaldıktan sonra sıçanlarda solunum yetersizliği ve akciğer fibrozunu araştırmak için yapıldı. Diğer bir amaç, erdosteinin antioksidan tedavi olarak terapötik etkisini araştırmaktı. Sıçanlar, dört hafta boyunca maden ortamına maruz bırakıldı ve daha sonra dört hafta boyunca temiz havada kaldılar. Sıçanların solunum fonksiyonları, in vivo olarak, sekiz hafta boyunca haftada bir kez kaydedildi. İşlem sonunda, akciğer dokusu seviyelerinin fibrozisi, oksidan / antioksidan durumu ve bronkoalveoler lavaj sıvılarında (BALF) inflamasyonun sitokinleri değerlendirildi.Bulgular: İkinci haftada kömür tozuna maruz kalan hayvanlarda solunum anormalliklerinin başladığı gözlendi. Dördüncü haftanın sonunda, solunum sıklığının artması ve solunum derinliğinin azalması vardı. Solunum yetersizlikleri temiz ortamda iyileşmedi, ayrıca altı haftanın sonunda (temiz havanın ikinci haftasında) apne ortaya çıktı. Hayvanlarda ölümler % 28 idi. Ratlara uygulanan Erdostein, akciğer toksisitesini tamamen ortadan kaldıramadı, ancak toksisitedeki şiddeti azalttı ve ayrıca erdostein uygulanan sıçanlarda ölen yoktu. Kömür tozuna maruz kalma, yüksek hidroksiprolin (HP) seviyelerine sahip fibrozis, yüksek interlökin-6 (IL-6) ve tümör nekroz faktörü-alfa (TNF-α) seviyelerinde sitokin iltihabı ve artmış malondialdehit (MDA) ile lipit peroksidasyonuyla sonuçlandı. Sağlıklı hayvanlara göre, endojen sülfit havuzları (GSH) dramatik bir şekilde tükendi ve artmış bir MPO aktivitesi tespit edildi. Yüksek biyokimyasal toksisite indeksi kısmen erdostein ile dengelenmiştir. Sonuç: Deneysel bulgularımız, ROS'un kömür işçilerinin pnömokonyozu oluşturduğu hipotezini desteklemektedir. Akciğer toksisitesini tersine çevirmek için yeniden oksijenasyon yarar sağlamaz. Üstelik, patogenezini daha da kötüleştiriyor. Bu nedenle, yeniden oksijenasyonun maden işçilerinde adım adım olması gerektiğini kuvvetle düşünüyoruz. Ek olarak, antioksidan tedavi, kısmen, maden işçilerinin kömür tozu kaynaklı akciğer toksisitesini tolere edebilmesi için bir seçenek olabilir.

Anahtar Kelimeler:

Solunum fonksiyonları, antioksidan tedavi, re-oksijenasyon, oksidatif stres, kömür madeni ambiyansı

Evaluation of lung toxicity in rats kept in coal mine ambience by in vivo respiration records: An Experimental Study

OBJECTIVE: Mine workers exposed to dusts or toxic gasses in occupational atmospheric conditions. Pneumoconiosis and other lung diseases are charecterized by the pathogenesis of coal dust-caused pulmonary toxicity associated with reactive oxygen species (ROS). MATERIALS AND METHODS: This study was conducted to investigate the respiration failures and fibrosis in rats after being exposed to coal dust and gases in mine atmosphere. Another aim was to study the therapeutic effect of erdosteine as antioxidant therapy. Rats were exposed to mine ambience for four week, and then they were breathed in the clean air for four week. The respiratory functions of rats were recorded once a week for eight week, as in vivo. The fibrosis of lung tissue levels, the oxidant/antioxidant status, and cytokines of inflammation in bronchoalveolar lavage fluids (BALFs) were evaluated, at the end of the processes.RESULTS: We observed to be the beginning of respiratory abnormalities in animals exposed to coal dust in second week. The end of fourth week, there were the increase of respiratory frequency and along with the decrease of respiratory depth. The respiratory failures were not improved in clean ambience, moreover apnea were appearance in the end of six week (the second week of clean air). Deaths were 28% in animals. Erdosteine administer to rats could not fully abolished to the pulmonary toxicity, however could able to hold to toxicity, and also there were not dies in rats administered to erdosteine. Coal dust exposure was resulted in fibrosis with higher hydroxyproline (HP) levels, cytokine inflammation with higher interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels, and lipid peroxidation with an increased malondialdehyde (MDA) levels, according to the healthy. A dramatically run out of endogen antidote sulfide pools (GSH), and an increased MPO activity were dedected in the mine dusts and gasses exposure group, according to the healthy animals. High biochemical index of toxicity were partly balanced by erdosteine. CONCLUSIONS: Our experimental findings support the hypothesis that ROS is induced coal workers' pneumoconiosis. Re-oxygenation cannot be getting it together to reverse the pulmonary toxicity. On the top of it, it can make its pathogenesis further exaggerating and even worse. On this account we heartily speculate that re-oxygenation should be by steps in mine workers. In addition the antioxidant therapy may be partly a choice be able to tolerate the coal dust-induced lung toxicity of mine workers.

Keywords:

Respiratory functions antioxidant therapy, , re-oxygenation, oxidative stress, coal mine ambience,

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References1. Zhang Q, Huang X. Induction of ferritin and lipid peroxidation by coal samples with different prevalence of coal workers’ pneumoconiosis: role of iron in the coals. Am. J. Ind. Med. 2002, 42: 171–179.
2. Pinho RA, Bonatto F, Andrades M, Frota ML Jr, Ritter C, Klamt F, et al. Lung oxidative response after acute coal dust exposure. Environ Res. 2004 Nov;96(3):290-7.
3. Nikula KJ, Vallyathan V, Green FH, Hahn FF. Influence of exposure concentration or dose on the distribution of particulate material in rat and human lungs. Environ Health Perspect. 2001 Apr;109(4):311-8.
4. Tao F, Gonzalez-Flecha B, Kobzik L: Reactive oxygen species in pulmonary inflammation by ambient particulates. Free Radic Biol Med 35(4): 327-340, 20035. Vanhee D, Gosset P, Boitelle A, Wallaert B, Tonnel AB: Cytokines and cytokine network in silicosis and coal workers' pneumoconiosis. Eur Respir J 8(5): 834-842, 1995.
6. Pinho RA, Silveira PC, Silva LA, Luiz Streck E, Dal-Pizzol F, F Moreira JC. N-acetylcysteine and deferoxamine reduce pulmonary oxidative stress and inflammation in rats after coal dust exposure. Environ Res. 2005 Nov;99(3):355-60.
7. Braga PC, Dal Sasso M, Zuccotti T: Assesment of the antioxidant activity of the SH metabolite I of erdosteine on human neutrophil oxidative bursts. Drug Res 50(8): 739-746, 2000.
8. Adams JD, Lauterburg BH, Mitchell JR. Plasma glutathione and glutathione disufide in the rat: regulation and response to oxidative stress. J. Pharmacol. Exp. Ther. 1983 227:749-754.
9. Ohkawa N, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 1979, 95:351-358.
10. Parlar A, Arslan SO, Doğan MF, Çam SA, Yalçin A, Elibol E, et al. The exogenous administration of CB2 specific agonist, GW405833, inhibits inflammation by reducing cytokine production and oxidative stress. Exp Ther Med. 2018 Dec;16(6):4900-4908.
11. Woessner JF Jr: The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. Arch Biochem Biophys 93: 440-447, 1961.
12. Tor M, Öztürk M, Altın R, Çımrın AH. Working conditions and pneumoconiosis in Turkish coal miners between 1985 and 2004: a report from Zonguldak coal basin, Turkey. Tüberküloz ve Toraks Dergisi 2010; 58(3): 252-260.
13. Castranova V, Vallyathan V: Silicosis and coal workers’ pneumoconiosis; Environ Health Perspect 108 (Suppl 4): 675-684, 2000.
14. Bowden DH: Macrophages, dust, and pulmonary diseases. Exp Lung Res 12(2): 89-107, 1987.
15. Vallyathan V, Mega JF, Shi X, Dalal NS: Enhanced generation of free radicals from phagocytes induced by mineral dusts. Am J Respir Cell Mol Biol 6(4): 404-413, 1992.
16. Srivastava PK, Singh Y, Misra UK: Pulmonary and hepatic glutathione levels, glutathione shuttle enzymes and lipid peroxidation in rats exposed intratracheally to coal fly ash. Biochem Int 17(3): 509-516, 1988.
17. Perrin-Nadif R, Auburtin G, Dusch M, Porcher JM, Mur JM: Blood antioxidant enzymes as markers of exposure or effect in coal miners. Occup Environ Med 53(1): 41-45, 1996.
18. Nadif R, Bourgkard E, Dusch M, Bernadac P, Bertrand JP, Mur JM, Pham QT: Relations between occupational exposure to coal mine dusts, erythrocyte catalase and Cu++/Zn++ superoxide dismutase activities, and the severity of coal workers' pneumoconiosis. Occup Environ Med 55(8): 533-540, 1998.
19. Arslan SO, Zerin M, Vural H and Coskun A: The effect of mela¬tonin on bleomycin induced pulmonary fibrosis in rats. J Pineal Res 32: 21 25, 2002.
20. Gosset P, Lassalle P, Vanhee D, Wallaert B, Aerts C, Voisin C, Tonnel AB: Production of tumor necrosis factor-alpha and interleukin-6 by human alveolar macrophages exposed in vitro to coal mine dust. Am J Respir Cell Mol Biol 5(5): 431-436, 1991.
21. Vanhee D, Gosset P, Marquette CH, Wallaert B, Lafitte JJ, Gosselin B, Voisin C, Tonnel AB: Secretion and mRNA expression of TNF alpha and IL-6 in the lungs of pneumoconiosis patients. Am J Respir Crit Care Med 152(1): 298-306, 1995.
22. Zhai R, Liu, G, Ge X, Bao W, Wu C, Yang, C, Liang D: Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and their soluble receptors in coal workers' pneumoconiosis. Respir Med 96(10): 829-834, 2002.
23. Yang LT, Liu X, Wu GH, Chen LF. Association between tumor necrosis factor-α -308 Gauss/A polymorphism and risk of silicosis and coal workers pneumoconiosis in Chinese population. Inhal Toxicol. 2018 May;30(6):213-217.
24. Arslan SO, Gelir E, Sayan H, Ozacmak VH. L-Arginine and melatonin interaction in rat intestinal ischemia--reperfusion. Fundam Clin Pharmacol. 2005 Oct;19(5):533-5.