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 100ppm 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 (6.25-50mg/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.