AEOL10150: A novel therapeutic for rescue treatment after toxic gas lung injury

New therapeutics designed as rescue treatments after toxic gas injury such as from chlorine (Cl-2) are an emerging area of interest. We tested the effects of the metalloporphyrin catalytic antioxidant AEOL10150, a compound that scavenges peroxynitrite, inhibits lipid peroxidation, and has SOD and catalase-like activities, on Cl-2-induced airway injury. Balb/C mice received 100 ppm Cl-2 gas for 5 min. Four groups were studied: Cl-2 only, Cl-2 followed by AEOL10150 1 and 9 h after exposure, AEOL10150 only, and control. Twenty-four hours after Cl-2 gas exposure airway responsiveness to aerosolized methacholine (6.25-50 mg/ml) was measured using a small-animal ventilator. Bronchoalveolar lavage (BAL) was performed to assess airway inflammation and protein. Whole lung tissue was assayed for 4-hydroxynonenal. In separate groups, lungs were collected at 72 h after Cl-2 injury to evaluate epithelial cell proliferation. Mice exposed to Cl-2 showed a significantly higher airway resistance compared to control, Cl-2/AEOL10150, or AEOL10150-only treated animals in response to methacholine challenge. Eosinophils, neutrophils, and macrophages were elevated in BAL of Cl-2-exposed mice. AEOL10150 attenuated the increases in neutrophils and macrophages. AEOL10150 prevented Cl-2-induced increase in BAL fluid protein. Chlorine induced an increase in the number of proliferating airway epithelial cells, an effect AEOL10150 attenuated. 4-Hydroxynonenal levels in the lung were increased after Cl-2 and this effect was prevented with AEOL10150. AEOL10150 is an effective rescue treatment for Cl-2-induced airway hyperresponsiveness, airway inflammation, injury-induced airway epithelial cell regeneration, and oxidative stress. (C) 2010 Elsevier Inc. All rights reserved.