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 (Cl2) 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 Cl2-induced airway injury. Balb/C mice received 100 ppm Cl2 gas for 5 min. Four groups were studied: Cl2 only, Cl2 followed by AEOL10150 1 and 9 h after exposure, AEOL10150 only, and control. Twenty-four hours after Cl2 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 Cl2 injury to evaluate epithelial cell proliferation. Mice exposed to Cl2 showed a significantly higher airway resistance compared to control, Cl2/AEOL10150, or AEOL10150-only treated animals in response to methacholine challenge. Eosinophils, neutrophils, and macrophages were elevated in BAL of Cl2-exposed mice. AEOL10150 attenuated the increases in neutrophils and macrophages. AEOL10150 prevented Cl2-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 Cl2 and this effect was prevented with AEOL10150. AEOL10150 is an effective rescue treatment for Cl2-induced airway hyperresponsiveness, airway inflammation, injury-induced airway epithelial cell regeneration, and oxidative stress.