Glucocorticoid pretreatment increases toxicity due to peroxides in alveolar epithelial-like cell lines.
In previous experiments an increase in zinc-mediated toxicity was found after pretreatment of alveolar epithelial type II-like cells with glucocorticoids. In this work toxicity of two peroxides (tertiary butyl hydroperoxide [tBHP], hydrogene peroxide [HP]) was assessed in L2 and A549 cells compared to dexamethasone (DEX) pretreated cells. Pretreatment of cells with 7.5micromol/l DEX for 72h decreased cellular glutathione content in both cell lines. Furthermore compared to not pretreated cells toxicity of both peroxides was increased in A549 cells, while in L2 cells only toxicity of tBHP was significantly increased by the glucocorticoid pretreatment. HP toxicity only showed a tendency to be increased in L2 cells after DEX pretreatment. The results point to a glucocorticoid-dependent increased oxidative stress of alveolar epithelial type II cells as antagonised by antioxidative enzymes such as catalase and/or preferentially by the glutathione system. This furthermore should be considered for all glucocorticoid applications in vivo as well.
Walther
Udo I
UI
Walther-Straub-Institut für Pharmakologie und Toxikologie der Ludwig-Maximilians-Universität München, Nussbaumstr. 26, 80336 München, Germany. udo.walther@med.uni-rostock.de
Stets
Regine
R
D000465:Algorithms; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D010545:Peroxides / Q000633:toxicity*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000187:drug effects*; D020122:tert-Butylhydroperoxide / Q000633:toxicity
D005938:Glucocorticoids; D010545:Peroxides; D011500:Protein Synthesis Inhibitors; D003907:Dexamethasone; D020122:tert-Butylhydroperoxide; D005980:Glutathione Reductase; D005978:Glutathione