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


Journal

Chemico-biological interactions
ISSN: 1872-7786
Titre abrégé: Chem Biol Interact
Pays: Ireland
ID NLM: 0227276

Informations de publication

Date de publication:
25 Jan 2019
Historique:
received: 11 06 2018
revised: 23 10 2018
accepted: 31 10 2018
pubmed: 6 11 2018
medline: 10 1 2019
entrez: 5 11 2018
Statut: ppublish

Résumé

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-1 cells) 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 300 μM SM and after 1 h treated with NSA (1, 5, 10 μM). 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.

Identifiants

pubmed: 30391637
pii: S0009-2797(18)30741-5
doi: 10.1016/j.cbi.2018.10.030
pii:
doi:

Substances chimiques

Acrylamides 0
Anti-Inflammatory Agents, Non-Steroidal 0
CXCL8 protein, human 0
IL6 protein, human 0
Interleukin-6 0
Interleukin-8 0
N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide 0
Protective Agents 0
Sulfonamides 0
Mustard Gas T8KEC9FH9P

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

80-85

Informations de copyright

Copyright © 2018 Elsevier B.V. All rights reserved.

Auteurs

Georg Menacher (G)

Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstraße 11, 80937, Munich, Germany.

Frank Balszuweit (F)

Bundeswehr Medical Command, 56070, Koblenz, Germany.

Simon Lang (S)

Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstraße 11, 80937, Munich, Germany.

Horst Thiermann (H)

Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstraße 11, 80937, Munich, Germany.

Kai Kehe (K)

Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstraße 11, 80937, Munich, Germany; Bundeswehr Medical Academy, Dept. Medical CBRN Defense, 80937, Munich, Germany.

Thomas Gudermann (T)

Walther-Straub-Institute of Pharmacology and Toxicology, Ludwig-Maximilian-University Munich, Goethestraße 33, 80336, Munich, Germany.

Annette Schmidt (A)

Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstraße 11, 80937, Munich, Germany; Bundeswehr University Munich, Faculty of Human Sciences, 85577, Neubiberg, Germany.

Dirk Steinritz (D)

Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstraße 11, 80937, Munich, Germany; Walther-Straub-Institute of Pharmacology and Toxicology, Ludwig-Maximilian-University Munich, Goethestraße 33, 80336, Munich, Germany.

Tanja Popp (T)

Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstraße 11, 80937, Munich, Germany; Walther-Straub-Institute of Pharmacology and Toxicology, Ludwig-Maximilian-University Munich, Goethestraße 33, 80336, Munich, Germany. Electronic address: tanjapopp@bundeswehr.org.

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Classifications MeSH