Effects of N-acetylcysteine stereoisomers on oxygen-induced lung injury in rats

Särnstrand, Bengt; Tunek, Anders; Sjödin, Karin; Hallberg, Anders

doi:10.1016/0009-2797(94)03332-3

Cited by 29 publications

(16 citation statements)

References 22 publications

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“…As NAC is rapidly eliminated in vivo, Särnstrand and colleagues proposed a higher antioxidative efficacy of NADC as compared to NAC [5]. Our data concerning H 2 O 2 toxicity underline this view.…”

Section: Discussionsupporting

confidence: 78%

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

Walther

Mückter

2009

Experimental Lung Research

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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.

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Section: Discussionsupporting

confidence: 78%

“…The D-enantiomer of NAC, lacking the role of a starting point for glutathione synthesis [4][5][6], was used as a reference to distinguish between direct antioxidative potency and indirect effects that might involve de novo biosynthesis of glutathione.…”

mentioning

confidence: 99%

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

Walther

Mückter

2009

Experimental Lung Research

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“…This contrasts the clear effect of NADC against oxygen injury as described in cell culture experiments by other authors [27,28]. In various cell types, decreases of antioxidative enzyme activities or increases of oxidative processes by glucocorticoids are described [29,30,31].…”

Section: Discussionmentioning

confidence: 54%

Enhancing Glutathione Synthesis can Decrease Zinc-Mediated Toxicity

Walther

Mückter

et al. 2008

Biol Trace Elem Res

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Zinc toxicity has been linked to cellular glutathione: A decrease in glutathione is followed by an increase in zinc-mediated toxicity. The question arises whether an increase in glutathione synthesis might decrease zinc-mediated cytotoxicity. We incubated five cell lines (hepatoma and lung-derived) with zinc chloride and 2 mmol/l N-acetyl-L-cysteine (NAC) to support glutathione synthesis. In all but one hepatic cell line, the glutathione content was increased by NAC as compared to the D-enantiomere NADC, whereas NADC did not increase GSH content as compared to not treated controls. In both alveolar epithelial cell lines, an increase in zinc tolerance was observed due to NAC as compared to NADC. In native fibroblast-like and the hepatoma cell lines, no changes in zinc tolerance were found due to NAC. In the fibroblast-like cells, zinc tolerance was increased due to NAC only after cellular glutathione had been previously decreased (by lowered cysteine concentrations in the medium). Enhancing glutathione synthesis can antagonize zinc-mediated toxicity in the alveolar epithelial cell lines, whereas some other characteristics than glutathione synthesis might be more important in other cell types. Furthermore, NAC acted as a GSH precursor only at cysteine medium concentrations of 10 micromol/l or below and therefore might be described as a poor cysteine repletor for glutathione synthesis.

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“…Recently, its antioxidant/radical-scavenging activity (4,5) has been the subject of considerable attention, in terms of extending its therapeutic applications.…”

Section: N-acetyl-l-cysteine (Nac)mentioning

confidence: 99%