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Open AccessArticle

Dimethyl Fumarate Attenuates Lung Inflammation and Oxidative Stress Induced by Chronic Exposure to Diesel Exhaust Particles in Mice

1
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21044-020, Brazil
2
Department of Molecular Pharmacology, University of Groningen, 9700 Groningen, The Netherlands
3
University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, 9700 Groningen, The Netherlands
4
Department of Histology and Embryology, Rio de Janeiro State University, Rio de Janeiro 20943-000, Brazil
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(24), 9658; https://doi.org/10.3390/ijms21249658
Received: 10 October 2020 / Revised: 13 December 2020 / Accepted: 17 December 2020 / Published: 18 December 2020
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Air pollution is mainly caused by burning of fossil fuels, such as diesel, and is associated with increased morbidity and mortality due to adverse health effects induced by inflammation and oxidative stress. Dimethyl fumarate (DMF) is a fumaric acid ester and acts as an antioxidant and anti-inflammatory agent. We investigated the potential therapeutic effects of DMF on pulmonary damage caused by chronic exposure to diesel exhaust particles (DEPs). Mice were challenged with DEPs (30 μg per mice) by intranasal instillation for 60 consecutive days. After the first 30 days, the animals were treated daily with 30 mg/kg of DMF by gavage for the remainder of the experimental period. We demonstrated a reduction in total inflammatory cell number in the bronchoalveolar lavage (BAL) of mice subjected to DEP + DMF as compared to those exposed to DEPs alone. Importantly, DMF treatment was able to reduce lung injury caused by DEP exposure. Intracellular total reactive oxygen species (ROS), peroxynitrite (OONO), and nitric oxide (NO) levels were significantly lower in the DEP + DMF than in the DEP group. In addition, DMF treatment reduced the protein expression of kelch-like ECH-associated protein 1 (Keap-1) in lung lysates from DEP-exposed mice, whereas total nuclear factor κB (NF-κB) p65 expression was decreased below baseline in the DEP + DMF group compared to both the control and DEP groups. Lastly, DMF markedly reduced DEP-induced expression of nitrotyrosine, glutathione peroxidase-1/2 (Gpx-1/2), and catalase in mouse lungs. In summary, DMF treatment effectively reduced lung injury, inflammation, and oxidative and nitrosative stress induced by chronic DEP exposure. Consequently, it may lead to new therapies to diminish lung injury caused by air pollutants. View Full-Text
Keywords: air pollution; diesel exhaust particles; dimethyl fumarate; inflammation; oxidative stress; lung; mice air pollution; diesel exhaust particles; dimethyl fumarate; inflammation; oxidative stress; lung; mice
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MDPI and ACS Style

Cattani-Cavalieri, I.; da Maia Valença, H.; Moraes, J.A.; Brito-Gitirana, L.; Romana-Souza, B.; Schmidt, M.; Valença, S.S. Dimethyl Fumarate Attenuates Lung Inflammation and Oxidative Stress Induced by Chronic Exposure to Diesel Exhaust Particles in Mice. Int. J. Mol. Sci. 2020, 21, 9658. https://doi.org/10.3390/ijms21249658

AMA Style

Cattani-Cavalieri I, da Maia Valença H, Moraes JA, Brito-Gitirana L, Romana-Souza B, Schmidt M, Valença SS. Dimethyl Fumarate Attenuates Lung Inflammation and Oxidative Stress Induced by Chronic Exposure to Diesel Exhaust Particles in Mice. International Journal of Molecular Sciences. 2020; 21(24):9658. https://doi.org/10.3390/ijms21249658

Chicago/Turabian Style

Cattani-Cavalieri, Isabella; da Maia Valença, Helber; Moraes, João A.; Brito-Gitirana, Lycia; Romana-Souza, Bruna; Schmidt, Martina; Valença, Samuel S. 2020. "Dimethyl Fumarate Attenuates Lung Inflammation and Oxidative Stress Induced by Chronic Exposure to Diesel Exhaust Particles in Mice" Int. J. Mol. Sci. 21, no. 24: 9658. https://doi.org/10.3390/ijms21249658

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