8-Isoprostane is an early biomarker for oxidative stress in chlorine-induced acute lung injury

Inhalation of chlorine (Cl-2) may cause oxidative acute lung injury (ALI) characterized by pulmonary edema, pneumonitis, and hyperreactive airways. The aim of the study was to identify possible biomarkers for Cl-2-induced ALI. Female BALB/c mice were exposed to Cl-2 for 15 min using two protocols 1) concentration-dependent response (25-200 ppm) and 2) time-kinetics (2h-14 days post-exposure). Exposure to 50-200 ppm Cl-2 caused a concentration-dependent inflammatory response with increased expression of IL-1 beta, IL-6 and CXCL1/KC in bronchoalveolar lavage fluid 2-6 h after exposure which was followed by increased lung permeability and a neutrophilic inflammation 12-24 h post-exposure. The early inflammatory cytokine response was associated with a clear but transient increase of 8-isoprostane, a biomarker for oxidative stress, with its maximum at 2 h after exposure. An increase of 8-isoprostane could also be detected in serum 2 h after exposure to 200 ppm Cl-2, which was followed by increased levels of IL-6 and CXCL1/KC and signs of increased fibrinogen and PAI-1. Melphalan, a non-oxidizing mustard gas analog, did not increase the 8-isoprostane levels, indicating that 8-isoprostane is induced in airways through direct oxidation by Cl-2. We conclude that 8-isoprostane represents an early biomarker for oxidative stress in airways and in the blood circulation following Cl-2-exposure.