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

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 an...

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Bibliographic Details
Published in:Toxicological sciences 2010-12, Vol.118 (2), p.521-529
Main Authors: Steinritz, Dirk, Bölck, Birgit, Schwarz, Jana, Balszuweit, Frank, Dühr, Sandra, Ibrahim, Marwa, Bloch, Wilhelm, Thiermann, Horst, Kehe, Kai
Format: Article
Language:English
Subjects:
Acetylcysteine - pharmacology
alpha-Linolenic Acid - pharmacology
Animals
Apoptosis - drug effects
Caspase 3 - metabolism
Cell Proliferation - drug effects
Cells, Cultured
Chemical Warfare Agents - toxicity
Drug Administration Schedule
Embryoid Bodies - drug effects
Embryoid Bodies - metabolism
embryoid body
Endothelial Cells - drug effects
Endothelial Cells - metabolism
Endothelial Cells - pathology
endothelial progenitor cells
Free Radical Scavengers - pharmacology
Ki-67 Antigen - metabolism
Mice
Mustard Gas - toxicity
N-acetyl cysteine
Neovascularization, Physiologic - drug effects
Neovascularization, Physiologic - physiology
Platelet Endothelial Cell Adhesion Molecule-1 - metabolism
sulfur mustard
Time Factors
wound healing
Wound Healing - drug effects
Wound Healing - physiology
α-linolenic acid
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Summary: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.
ISSN:1096-6080
1096-0929
DOI:10.1093/toxsci/kfq271