Dibutil Ftalatın İnsan Akciğer Hücre Hattına Toksik Etkilerinin Değerlendirilmesi ve Askorbik Asit ve N-Asetilsisteinin Olası Koruyucu Etkileri

Abstract

Endocrine disruptings are chemical substances which are generally produced by humans that disrupt the normal functioning of the body by imitating or blocking hormones. The mostly studied phthalate derivative is di(2-ethylhexyl) phthalate (DEHP). It is known that DEHP can lead particularly to testicular and hepatic oxidative stress. Dibutylphthalate (DBP), which is the most widely used phthalate derivative after DEHP, is widely used in many fields, particularly in cosmetics (especially nail polishes). Manicurists, individuals who use perfumes and deodorants intensely and people working in phthalate producing plants are known to be exposed to DBP particularly by inhalation. Although there is data on testicular and hepatic toxicity of DBP in the literature, there are very few studies on its lung toxicity. In addition, lung toxicity mechanisms of DBP are not known. In this thesis, we aimed to evaluate the possible cytotoxic and oxidative stress-generating effects of DBP in human non-small cell lung cancer cell cultures (A549 cells). In this context, inhibitor concentration 30 (IC30; concentration that kills 30% of cells) and inhibitor concentration 50 (IC50; concentration that kills 50% of cells) doses were determined in A549 cells and the effect of intracellular reactive oxygen species (ROS) generating effect by IC30 dose was evaluated. In addition, possible lipid peroxidation and protein oxidation caused by DBP were investigated, possible alterations in glutathione (GSH), which is the most important thiol in the organism, and total antioxidant capacity (TAOC) levels were identified. In the thesis, the protective effects of ascorbic acid (Asc) and N-acetylcysteine (NAC) against the possible toxic effects of DBP were determined. Both NAC and Asc along with DBP application reduced ROS levels, decreased protein oxidation, increased total GSH levels to control levels and both antioxidants reduced TAOC levels due to decreased oxidative stress. According to the data obtained at the end of the thesis, one of the underlying toxicity mechanisms of DBP is oxidative stress. In addition, Asc acid and NAC were determined to be protective against oxidative stress caused by DBP.