Abstract | BACKGROUND: RESULTS: We found that 10 mM NAC, when administered simultaneously or prior to treatment with 500 muM CEES, increased the viability of LPS stimulated macrophages. Surprisingly, NAC failed to protect LPS stimulated macrophages from CEES induced loss of NO production. Macrophages treated with both LPS and CEES show increased oxidative stress parameters (cellular thiol depletion and increased protein carbonyl levels). NAC effectively protected RAW 264.7 cells simultaneously treated with CEES and LPS from GSH loss and oxidative stress. Polymyxin B was found to partially block nitric oxide production and diminish CEES toxicity in LPS-treated macrophages. CONCLUSION: The present study shows that oxidative stress is an important mechanism contributing to CEES toxicity in LPS stimulated macrophages and supports the notion that antioxidants could play a therapeutic role in preventing mustard gas toxicity. Although NAC reduced oxidative stress in LPS stimulated macrophages treated with CEES, it did not reverse CEES-induced loss of NO production. NAC and polymyxin B were found to help prevent CEES toxicity in LPS-treated macrophages.
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Authors | Victor Paromov, Min Qui, Hongsong Yang, Milton Smith, William L Stone |
Journal | BMC cell biology
(BMC Cell Biol)
Vol. 9
Pg. 33
(Jun 20 2008)
ISSN: 1471-2121 [Electronic] England |
PMID | 18570648
(Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Free Radical Scavengers
- Lipopolysaccharides
- Nitric Oxide
- 2-chloroethyl ethyl sulfide
- Glutathione
- Polymyxin B
- Mustard Gas
- Acetylcysteine
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Topics |
- Acetylcysteine
(pharmacology)
- Animals
- Cell Survival
- Free Radical Scavengers
(pharmacology)
- Glutathione
(metabolism)
- Lipopolysaccharides
(pharmacology)
- Macrophages
(drug effects, metabolism)
- Mice
- Microscopy, Fluorescence
- Mustard Gas
(analogs & derivatives, toxicity)
- Nitric Oxide
(biosynthesis)
- Oxidative Stress
- Polymyxin B
(pharmacology)
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