Effect of N-acetyl cysteine and alpha-linolenic acid on sulfur mustard caused impairment of in vitro endothelial tube formation.

Abstract

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.

• Authors: Dirk Steinritz, Birgit Bölck, Jana Schwarz, Frank Balszuweit, Sandra Dühr, Marwa Ibrahim, Wilhelm Bloch, Horst Thiermann, Kai Kehe
• Journal: Toxicological sciences : an official journal of the Society of Toxicology (Toxicol Sci) Vol. 118 Issue 2 Pg. 521-9 (Dec 2010) ISSN: 1096-0929 [Electronic] United States
• PMID: 20833707 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemical Warfare Agents
• Free Radical Scavengers
• Ki-67 Antigen
• Platelet Endothelial Cell Adhesion Molecule-1
• alpha-Linolenic Acid
• Casp3 protein, mouse
• Caspase 3
• Mustard Gas
• Acetylcysteine

Topics

• Acetylcysteine (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, metabolism)
• Endothelial Cells (drug effects, metabolism, pathology)
• Free Radical Scavengers (pharmacology)
• Ki-67 Antigen (metabolism)
• Mice
• Mustard Gas (toxicity)
• Neovascularization, Physiologic (drug effects, physiology)
• Platelet Endothelial Cell Adhesion Molecule-1 (metabolism)
• Time Factors
• Wound Healing (drug effects, physiology)
• alpha-Linolenic Acid (pharmacology)