Comparative study on the selenium- and N-acetylcysteine-related effects on the toxic action of hyperoxia, paraquat and the enzyme reaction hypoxanthine-xanthine oxidase in cultured endothelial cells.
The potential protective effect of N-acetylcysteine against various types of oxidative stress (exposure to hyperoxia, treatment with paraquat, incubation in the presence of the hypoxanthine-xanthine oxidase system) was tested in primary cultures of porcine aortic endothelial cells. It was compared to that of selenomethionine (Se-Met), known to increase glutathione peroxidase activity, when given either alone or in combination with N-acetylcysteine. LDH release, 3H-thymidine (TdR) incorporation into DNA and DNA content were measured to assess the cytotoxic effect of the conditions tested. Total and oxidized glutathione content was also determined. Whereas Se-Met had a partial protective effect on all the conditions but paraquat treatment, N-acetylcysteine administration had no effect on the hyperoxia induced changes and significantly worsened the cytotoxic action of paraquat. On the other hand, LDH release following an incubation in the presence of the hypoxanthine-xanthine oxidase was significantly reduced after N-acetylcysteine treatment. No major change in total nor in oxidized glutathione followed N-acetylcysteine treatment in control and experimental conditions. A dose-dependent protective effect of N-acetylcysteine was obtained when this agent was given concomitantly with the xanthine oxidase system. These data suggest that in cultured endothelial cells a N-acetylcysteine-related protective effect, if present, is most likely to result from the direct scavenging action of N-acetylcysteine.
Respiratory Division, Hôpital cantonal universitaire, Geneva, Switzerland.
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Junod
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Jornot
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Grichting
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D004247:DNA / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology; D066298:In Vitro Techniques; D010100:Oxygen / Q000633:toxicity*; D010269:Paraquat / Q000633:toxicity*; D012643:Selenium / Q000494:pharmacology*; D012645:Selenomethionine / Q000494:pharmacology; D013552:Swine; D014969:Xanthine Oxidase / Q000378:metabolism*
D004247:DNA; D012645:Selenomethionine; D014969:Xanthine Oxidase; D012643:Selenium; D010269:Paraquat; D010100:Oxygen; D000111:Acetylcysteine