Gamze KARAMAN, Aylin BALCI, Erhan TAN, Anıl YİRÜN, Ünzile SUR, Belma KOÇER GÜMÜŞEL, Pınar ERKEKOĞLU

DİBUTİL FTALATIN İNSAN AKCİĞER HÜCRE HATTINA OLASI TOKSİK ETKİLERİNİN DEĞERLENDİRİLMESİ VE ASKORBİK ASİT VE N-ASETİLSİSTEİNİN OLASI KORUYUCU ETKİLERİ

Endokrin bozucu kimyasallar (EBK’ler), hormonların üretimini, salınımını, biyotransformasyonunu ve/veya atılımını etkileyen sentetik veya doğal kimyasal maddelerdir. Dibutilftalat (DBP) endüstride birçok alanda yaygın olarak kullanımı olan bir ftalat türevidir. Literatürde DBP'nin testiküler ve hepatik toksisitesine dair veriler olmakla birlikte, akciğer toksisitesi üzerinde çok az sayıda çalışma bulunmaktadır. Ayrıca, DBP’nin akciğer toksisite mekanizmaları bilinmemektedir. Bu çalışmada, DBP’nin insan küçük hücreli olmayan akciğer kanseri hücre kültürleri (A549 hücreleri) üzerinde olası sitotoksik ve oksidatif stres oluşturucu etkilerinin değerlendirilmesi amaçlanmıştır. Bu kapsamda, A549 hücrelerinde DBP’nin inhibitör konsantrasyon 30 (IC30) dozu belirlenmiş, IC30 dozunun neden olduğu intraselüler reaktif oksijen türleri (ROS)’u arttırıcı etkisi değerlendirilmiştir. Ayrıca, DBP’nin yol açtığı olası lipit peroksidasyon ve protein oksidasyonu incelenmiş, glutatyon (GSH) ve total antioksidan kapasitede (TAOC) düzeylerinde yol açabileceği olası değişiklikler belirlenmiştir. Çalışmada DBP'nin olası toksik etkilerine karşı askorbik asit (Asc) ve N-asetil sisteinin (NAC) olası koruyucu etkileri incelenmiştir. Hem NAC, hem de Asc’nin DBP uygulamasıyla beraber ROS düzeylerini düşürdüğü, protein oksidasyonunu azalttığı, total GSH düzeylerini yükselttiği ve azalan oksidatif strese bağlı olarak her iki antioksidanın da TAOC düzeylerini düşürdüğü belirlenmiştir. Elde edilen bilgiler doğrultusunda, DBP’nin toksik etki mekanizmasının altında yatan nedenlerden birinin oksidatif stres olduğu anlaşılmıştır. Ayrıca, Asc ve NAC’ın DBP’nin neden olduğu oksidatif strese karşı koruyucu oldukları saptanmıştır.

Anahtar Kelimeler:

Dibutilftalat (DBP), insan akciğer hücreleri (A549 hücreleri), askorbik asit, N-asetilsistein, oksidatif stres, sitotoksisite, reaktif oksijen türleri (ROS), Ascorbic acid, Dibutylphthalate (DBP), Human lung cancer cells (A549 cells), N-acetylcysteine, Oxidative stress

ASSESSMENT OF TOXIC EFFECTS OF DIBUTYL PHTHALATE ON HUMAN LUNG CELL LINE AND POSSIBLE PROTECTIVE EFFECTS OF ASCORBIC ACID AND N-ACETYLCYSTEINE

Endocrine-disrupting chemicals (EDCs) are chemicals that affect production, release, biotransformation or excretion of hormones. Dibutylphthalate (DBP) is a phthalate derivative, which used in many fields in industry. Although there is data on testicular and hepatic toxicity of DBP in the literature, there are few studies on lung toxicity. In this study, we aimed to evaluate the possible cytotoxic and oxidative stress-generating effects of DBP in human non-small cell lung cancer cell line (A549 cells). Inhibitor concentration 30 was determined in A549 cells and the effect of intracellular reactive oxygen species (ROS) generating effect was evaluated. Also, possible lipid peroxidation and protein oxidation caused by DBP were investigated, possible alterations in glutathione (GSH), and total antioxidant capacity (TAOC) levels were identified. In the study, the protective effects of ascorbic acid (Asc) and N-acetyl cysteine (NAC) against the possible toxic effects of DBP were determined. Both NAC and Asc along with DBP application reduced ROS and TAOC levels, decreased protein oxidation, and increased total GSH levels due to decreased oxidative stress. According to our data, one of the underlying toxicity mechanisms of DBP is oxidative stress. In addition, Asc and NAC were determined to be protective against oxidative stress caused by DBP.

Keywords:

Ascorbic acid, Dibutylphthalate (DBP), Human lung cancer cells (A549 cells), N-acetylcysteine, Oxidative stress,

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