Cytotoxicity and the levels of oxidative stress parameters in WI38 cells following 2 macrocyclic crown ethers treatment

Background: Crown ethers as macrocyclic polyethers possess a hydrophilic cavity surrounded by hydrophobic ring which enable them to diffuse cell membrane. We evaluated cytotoxicity effects of 15-crown-5 and 18-crown-6 and the role of oxidative stress in WI38 cells culture. Methods: The effect of these ethers in a range of doses (0.1 to 2 mmol/l) on the activity of antioxidant enzymes; superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT), and on some macromolecules oxidative damages end products; malondialdehyde (MDA) and dityrosine were assessed by spectrometry and HPLC methods. Results: Both compounds markedly inhibited the viability of cells with respect to control particularly at doses >0.5 mmol/l after 24- or 48 h incubation. The survivals of cells were measured using MTT assay. They lowered cell's viability and significantly promoted ROS generation, increased enzyme activities and enhanced oxidative damages in which 18-crown-6 was more effective. Treating cells with 30 mu m of alpha-tocopherol in addition to 2 mmol/l of crown ethers showed significant decrease on the levels of ROS, enzyme activities, MDA and dityrosine. Conclusion: We document the oxidative radicals forming ability of the studied crown ethers and further strengthens the documentation of their cytotoxicity effects through lipid and proteins oxidation damages. (C) 2005 Elsevier B.V. All rights reserved.