Walther Udo I, Mückter Harald
Institut fur Toxikologie und Pharmakologie, Universität Rostock, Rostock, Germany.
Exp Lung Res. 2009 Mar;35(2):89-103. doi: 10.1080/01902140802441569.
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.
对N-乙酰半胱氨酸（NADC、NAC）的D型和L型进行了测试，以评估其在两种肺细胞系中对抗过氧化氢（H₂O₂）或叔丁基过氧化氢（tBHP）介导的毒性的能力，从而评估谷胱甘肽合成对过氧化物的有效性。通过蛋氨酸掺入、总谷胱甘肽含量以及谷胱甘肽二硫化物与谷胱甘肽的比率来评估毒性。与未处理的细胞相比，2 mmol/L的NAC或NADC分别使A549或L2细胞中的细胞谷胱甘肽增加约1.5倍或3倍（NAC）以及1.1倍或1.2倍（NADC）。NADC降低了H₂O₂介导的毒性（与对照组相比），但NAC使其略有增加，而NAC和NADC均降低了tBHP介导的毒性。然而，与对照组相比，NADC仅在L2细胞中是tBHP的有效解毒剂。地塞米松预处理增加了L2细胞中H₂O₂和tBHP的毒性，但不影响NAC/NADC的抗氧化功效。尽管两种情况下谷胱甘肽氧化还原系统存在显著差异，但NAC/NADC在两种细胞系中的解毒特性相似。因此，可以得出结论，NAC和NADC的直接抗氧化特性是基于H₂O₂的毒性的主要拮抗因素，但不是tBHP介导的毒性的主要拮抗因素。在两种肺细胞系中，谷胱甘肽生物合成的增强降低了tBHP的毒性，但未降低H₂O₂的毒性。
