Dimethyl fumarate attenuates lung inflammation and oxidative stress induced by chronic exposure to diesel exhaust particles in mice

Abstract

<b>Background:</b> Air pollution is caused mainly by diesel burning and is associated to increased morbidity and mortality due the potential adverse health effects caused by inflammation and oxidative stress. Dimethyl fumarate (DMF) is a fumaric acid ester and acts as an anti-oxidative and anti-inflammatory. We aimed to investigate the therapeutic effect of DMF against pulmonary damage caused by diesel exhaust particles (DEP) chronic exposure of mice. <b>Methods:</b> Mice were treated with DEP (30 μg/mice) of by intranasal instillation over 60 consecutive days. After day 30, the animals were treated with 30 mg/kg of DMF by gavage until the end of the experiment. <b>Results:</b> We demonstrated the reduction of total cell number in DEP+DMF than in DEP group. Importantly, DMF treatment was able to reduce the lung injury caused by DEP exposure. Intracellular total ROS, peroxynitrite (OONO) and nitric oxide (NO) levels reduced in DEP+DMF than in DEP group. The protein expression of kelch-like ECH-associated protein 1 (Keap-1) and nuclear factor κB (NF-κB) reduced in DEP+DMF compared to DEP group. NF-κB decreased in DEP+DMF than in control group. Nitrotyrosine, glutathione peroxidase-1/2 (GPx-1/2) and catalase expression decreased in DEP+DMF than in DEP group. <b>Conclusion:</b> In conclusion, our study is the first to demonstrates that treatment with DMF effectively ameliorates DEP-induced lung injury, inflammation, and oxidative and nitrosative stress. Since air pollution poses a common and serious health threat world-wide, the identification of DMF as a potent antioxidant and anti-inflammatory agent in the lungs could benefit the development of therapeutic approaches against airway pollution-associated malignancies.