Journal Article

Effect of N-Acetyl Cysteine and α-Linolenic Acid on Sulfur Mustard Caused Impairment of <i>In Vitro</i> Endothelial Tube Formation

Dirk Steinritz, Birgit Bölck, Jana Schwarz, Frank Balszuweit, Sandra Dühr, Marwa Ibrahim, Wilhelm Bloch, Horst Thiermann and Kai Kehe

in Toxicological Sciences

Volume 118, issue 2, pages 521-529
Published in print December 2010 | ISSN: 1096-6080
Published online September 2010 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfq271
Effect of N-Acetyl Cysteine and α-Linolenic Acid on Sulfur Mustard Caused Impairment of In Vitro Endothelial Tube Formation

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Sulfur mustard (SM), an alkylating chemical warfare agent, leads to tissue damage, including inflammation, blister formation, and impaired wound healing. Especially wound healing is of concern because after SM exposure, wound healing is prolonged. In this study, we focused on the effect of SM (30 and 100μM) on endothelial tube formation, apoptosis, and proliferation in mouse embryoid bodies (EBs), which provide an appropriate model for investigating vasculogenesis and angiogenesis. EBs were exposed to SM for 30 min on day 0, 3, or 6 of EBs’ growth, were allowed to grow until day 7, then fixed, and immunostained (PECAM-1, Ki67, and activated caspase-3). SM significantly decreased endothelial tube formation compared with unexposed EBs. Additionally, we observed a significant increase of apoptosis. As the formation of reactive oxygen species (ROS) is discussed to be involved in the pathophysiology of SM toxicity, we evaluated the effect of ROS scavengers (α-linolenic acid [ALA] and N-acetyl cysteine [NAC]) in the same experimental setup. Temporary effects of both scavengers could be detected, in particular NAC seemed to have temporary significant positive effects on endothelial tube formation in 100μM SM–exposed EBs. ALA augmented proliferation when administered after 30μM SM exposure on day 3, whereas NAC treatment on day 0 decreased apoptosis induced by 100μM SM. Taken together, our findings pointed to a negative effect of SM on vascularization and endothelial tube formation. ROS scavengers NAC and ALA showed temporary, but not long-lasting, rescuing effects regarding endothelial tube formation after SM exposure.

Keywords: sulfur mustard; N-acetyl cysteine; α-linolenic acid; endothelial progenitor cells; embryoid body; wound healing

Journal Article.  5072 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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