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标题：Formation of chlorinated lipids post-chlorine gas exposure
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作者：David A. Ford ; Jaideep Honavar ; Carolyn J. Albert 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2016
卷号：57
期号：8
页码：1529-1540
DOI：10.1194/jlr.M069005
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Exposure to chlorine (Cl₂) gas can occur during accidents and intentional release scenarios. However, biomarkers that specifically indicate Cl₂ exposure and Cl₂-derived products that mediate postexposure toxicity remain unclear. We hypothesized that chlorinated lipids (Cl-lipids) formed by direct reactions between Cl₂ gas and plasmalogens serve as both biomarkers and mediators of post-Cl₂ gas exposure toxicities. The 2-chloropalmitaldehyde (2-Cl-Pald), 2-chlorostearaldehyde (2-Cl-Sald), and their oxidized products, free- and esterified 2-chloropalmitic acid (2-Cl-PA) and 2-chlorostearic acid were detected in the lungs and plasma of mouse and rat models of Cl₂ gas exposure. Levels of Cl-lipids were highest immediately post-Cl₂ gas exposure, and then declined over 72 h with levels remaining 20- to 30-fold higher at 24 h compared with baseline. Glutathione adducts of 2-Cl-Pald and 2-Cl-Sald also increased with levels peaking at 4 h in plasma. Notably, 3-chlorotyrosine also increased after Cl₂ gas exposure, but returned to baseline within 24 h. Intranasal administration of 2-Cl-PA or 2-Cl-Pald at doses similar to those formed in the lung after Cl₂ gas exposure led to increased distal lung permeability and inflammation and systemic endothelial dysfunction characterized by loss of eNOS-dependent vasodilation. These data suggest that Cl-lipids could serve as biomarkers and mediators for Cl₂ gas exposure and toxicity.
关键词：inflammation ; kinetics ; lipids/oxidation ; lung ; nitric oxide