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Early oxidative stress, DNA damage and inflammation resulting from subcutaneous injection of sulfur mustard into mice

TitleEarly oxidative stress, DNA damage and inflammation resulting from subcutaneous injection of sulfur mustard into mice
Publication TypeJournal Article
Year of Publication2017
AuthorsZhang X., Mei Y., Wang T., Liu F., Jiang N., Zhou W., Zhang Y.
JournalEnviron Toxicol Pharmacol
Volume55
Pagination68-73
Date PublishedOct
ISBN Number1382-6689 (Linking)
Accession Number28830012
Keywords*DNA Damage, *Oxidative Stress, Animals, Cytokine, Cytokines/metabolism, Deoxyguanosine/analogs & derivatives/metabolism, Gene Expression Regulation/drug effects, Inflammation/*chemically induced/genetics/metabolism, Injections, Subcutaneous, Male, Mice, Mustard Gas/*toxicity, Oxidative stress, Phosphorylated histone 2A.X, Reactive Oxygen Species, Reactive Oxygen Species/metabolism, Sulfur Mustard
Abstract

Oxidative stress, DNA damage repair, and inflammation are three important reactions of sulfur mustard (SM) exposure. But molecular related chronological events in the earlier stage of SM exposure model are still unclear. In the research, reactive oxygen species (ROS) was measured by using flow cytometry. Cytokines were tested in Luminex method. Myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), 8-hydroxy-2-deoxyguanosine (8-OHdG) and glutathione (GSH) activity or levels in serum were determined by commercially available kits. Western blot was used to determination of phosphorylated histone 2A.X (gamma-H2A.X). Results showed that the oxidative stress biomarker of ROS and 8-OHdG were significantly increased early at 0.5h of SM exposure, but GSH level was decreased at 0.5h. Similarly, SM increased gamma-H2A.X level early at 2h, which reached to peak at 8h and recovered to normal at 24h. MPO and iNOS activity were also increased early at 2h and 0.5h respectively. However, all selected inflammation biomarkers, including IL-6, TNF-alpha, IL-1beta, MCP-1, GM-CSF and IL-10 concentrations are all unchangeable in 2h. The results indicated that oxidative stress and DNA damage had happened more quickly than inflammation reaction. These chronological events may be due to uncovered generation of reactive oxygen species, DNA alkylation and oxidative DNA damage. In conclusion, this research showed that both oxidative stress and DNA damage are earlier events than inflammation in sulfur mustard toxic mouse model.

URLhttps://www.ncbi.nlm.nih.gov/pubmed/28830012
DOI10.1016/j.etap.2017.06.016
Short TitleEarly oxidative stress, DNA damage and inflammation resulting from subcutaneous injection of sulfur mustard into mice

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