Formation of chlorinated lipids post-chlorine gas exposure

Exposure to chlorine (Cl-2) gas can occur during accidents and intentional release scenarios. However, biomarkers that specifically indicate Cl-2 exposure and Cl-2-derived products that mediate postexposure toxicity remain unclear. We hypothesized that chlorinated lipids (Cl-lipids) formed by direct reactions between Cl-2 gas and plasmalogens serve as both biomarkers and mediators of post-Cl-2 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 Cl-2 gas exposure. Levels of Cl-lipids were highest immediately post-Cl-2 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 Cl-2 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 Cl-2 gas exposure led to increased distal lung permeability and inflammation and systemic endothelial dysfunction characterized by loss of eNOS-dependent vasodilation.(jlr) These data suggest that Cl-lipids could serve as biomarkers and mediators for Cl-2 gas exposure and toxicity.-Ford, D. A., J. Honavar, C. J. Albert, M. A. Duerr, J. Y. Oh, S. Doran, S. Matalon, and R. P. Patel. Formation of chlorinated lipids post-chlorine gas exposure.