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Necrosulfonamide - Unexpected effect in the course of a sulfur mustard intoxication

TitleNecrosulfonamide - Unexpected effect in the course of a sulfur mustard intoxication
Publication TypeJournal Article
Year of Publication2019
AuthorsMenacher G., Balszuweit F., Lang S., Thiermann H., Kehe K., Gudermann T., Schmidt A., Steinritz D., Popp T.
JournalChem Biol Interact
Volume298
Pagination80-85
Date PublishedJan 25
ISBN Number0009-2797 (Linking)
Accession Number30391637
KeywordsAcrylamides/*pharmacology, Anti-Inflammatory Agents, Non-Steroidal/pharmacology, Apoptosis, Apoptosis/drug effects, Cell Line, Coculture Techniques, Humans, Interleukin, Interleukin-6/metabolism, Interleukin-8/metabolism, Mustard Gas/*toxicity, Necroptosis, NECROSIS, Necrosis/drug therapy, Necrosulfonamide, Protective Agents/*pharmacology, Sulfonamides/*pharmacology, Sulfur Mustard
Abstract

Although its first military use in Ypres was 100 years ago, no causal therapy for sulfur mustard (SM) intoxications exists so far. To improve the therapeutic options for the treatment of SM intoxications, we developed a co-culture of keratinocytes (HaCaT cells) and immunocompetent cells (THP-1cells) to identify potential substances for further research. Here, we report on the influence of necrosulfonamide (NSA) on the course of a SM intoxication in vitro. The cells were challenged with 100, 200 and 300muM SM and after 1h treated with NSA (1, 5, 10muM). NSA was chosen for its known ability to inhibit necroptosis, a specialized pathway of programmed necrosis. However, in our settings NSA showed only mild effects on necrotic cell death after SM intoxication, whereas it had an immense ability to prevent apoptosis. Furthermore, NSA was able to reduce the production of interleukin-6 and interleukin-8 at certain concentrations. Our data highlight NSA as a candidate compound to address cell death and inflammation in SM exposure.

URLhttps://www.ncbi.nlm.nih.gov/pubmed/30391637
DOI10.1016/j.cbi.2018.10.030
Short TitleNecrosulfonamide - Unexpected effect in the course of a sulfur mustard intoxication

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