Glutathione Synthesis Against Oxidant Injury by Peroxides in Two Alveolar Epithelial Cell Lines

Abstract

The D- and L-forms of N-acetylcysteine (NADC, NAC) were tested in antagonizing the toxicity mediated by hydrogen peroxide (H(2)O(2)) or tertiary butyl hydroperoxide (tBHP) in two lung cell lines to assess the effectivity of glutathione synthesis against peroxides. Toxicity was assessed by methionine incorporation, total glutathione content, and glutathione disulfide to glutathione ratio. NAC or NADC, at 2 mmol/L, increased cellular glutathione to about 1.5- or 3-fold (NAC) and 1.1- or 1.2-fold (NADC) in A549 or L2 cells, respectively, as compared to naive cells. H(2)O(2)-mediated toxicity was decreased by NADC (as compared to controls), but increased slightly with NAC, whereas tBHP-mediated toxicity was decreased both by NAC and NADC. However, when compared to controls, NADC was an effective antidote against tBHP in L2 cells only. Dexamethasone pretreatment increased toxicity of H(2)O(2) and tBHP in L2 cells, but did not affect the antioxidative efficacy of NAC/NADC. Antidotal properties of NAC/NADC were similar in both cell lines, despite significant differences of the glutathione redox system in both situations. Hence, it is concluded that direct antioxidative properties of NAC and NADC is a main antagonizing factor in H(2)O(2)-based toxicity but not in tBHP-mediated toxicity. Enhancement of glutathione biosynthesis decreased toxicity of tBHP, but not of H(2)O(2) in 2 pulmonary cell lines.

1,4-Benzoquinone (PBQ) Induced Toxicity in Lung Epithelial Cells Is Mediated by the Disruption of the Microtubule Network and Activation of Caspase-3

“…N -Acetylcysteine (NAC) is a thiol containing cell permeable antioxidant, which acts as the precursor of l -cysteine and reduced glutathione. Administration of NAC was reported to increase the intracellular levels of GSH in the A549 cells , and this leads to the improvement of the intracellular redox environment. N -Acetyl cysteine was reported to be effective against cigarette smoke induced pathogenesis in lung cells , .…”