Formation of chlorinated lipids post-chlorine gas exposure.
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.
Department of Biochemistry and Molecular Biology and Center for Cardiovascular Research, Saint Louis University, St. Louis, MO.
David A
DA
Ford
Departments of Pathology, University of Alabama at Birmingham, Birmingham, AL.
Jaideep
J
Honavar
Department of Biochemistry and Molecular Biology and Center for Cardiovascular Research, Saint Louis University, St. Louis, MO.
Carolyn J
CJ
Albert
Department of Biochemistry and Molecular Biology and Center for Cardiovascular Research, Saint Louis University, St. Louis, MO.
Mark A
MA
Duerr
Departments of Pathology, University of Alabama at Birmingham, Birmingham, AL.
Joo Yeun
JY
Oh
Anesthesiology, University of Alabama at Birmingham, Birmingham, AL.
Stephen
S
Doran
Anesthesiology, University of Alabama at Birmingham, Birmingham, AL Centers for Free Radical Biology University of Alabama at Birmingham, Birmingham, AL Lung Injury and Repair, University of Alabama at Birmingham, Birmingham, AL.
Sadis
S
Matalon
Departments of Pathology, University of Alabama at Birmingham, Birmingham, AL Centers for Free Radical Biology University of Alabama at Birmingham, Birmingham, AL Lung Injury and Repair, University of Alabama at Birmingham, Birmingham, AL rakeshpatel@uabmc.edu.
Rakesh P
RP
Patel
D055371:Acute Lung Injury / Q000097:blood / Q000139:chemically induced; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D002713:Chlorine / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D054879:Halogenation; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000097:blood*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009503:Neutropenia / Q000097:blood; D051381:Rats; D014664:Vasodilation / Q000187:drug effects
D000447:Aldehydes; D008055:Lipids; D002713:Chlorine; D005978:Glutathione
inflammation; kinetics; lipids/oxidation; lung; nitric oxide