Role of Nrf2 in inflammatory response in lung of mice exposed to zinc oxide nanoparticles
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(2019) 16:47
RESEARCH
Open Access
Role of Nrf2 in inflammatory response in lung of mice exposed to zinc oxide nanoparticles Radwa Sehsah1,8, Wenting Wu1, Sahoko Ichihara2, Naozumi Hashimoto3, Yoshinori Hasegawa3, Cai Zong4, Ken Itoh5, Masayuki Yamamoto6, Ahmed Ali Elsayed7, Soheir El-Bestar8, Emily Kamel8 and Gaku Ichihara1,4*
Abstract Background: Zinc oxide nanoparticles (ZnO-NPs) are widely used in many industrial sectors and previous studies have reported that exposure of the lungs to ZnO-NPs induces both acute and/or chronic pulmonary inflammation, but the exact mechanism underlying such response remains elusive. This study investigated the role of nuclear factor-erythroid 2-related factor (Nrf2) in pulmonary inflammation induced by exposure to ZnO-NPs using Nrf2 null (Nrf2−/−) mice. Methods: Twenty-four male Nrf2−/− mice and thirty male wild type C57BL/6 J mice were divided into three groups of eight and ten each respectively, and exposed once to ZnO-NPs at 0, 10, 30 μg/mouse by pharyngeal aspiration. At 14 days after the exposure to ZnO-NPs, bronchoalveolar lavage fluid (BALF) and lungs were collected to quantify protein level and the number of inflammatory cells. The mRNA levels of Nrf2-dependent antioxidant enzymes and inflammatory cytokines in lung tissue were measured. Results: Exposure to ZnO-NPs dose-dependently increased the number of total cells, macrophages, lymphocytes and eosinophils in BALF both in Nrf2−/− mice and wild type mice, but the magnitude of increase was significantly higher in Nrf2−/− mice than wild type mice. The number of neutrophils in BALF increased in Nrf2−/− mice, being accompanied by marginal trend of increase in mRNA expression of MIP-2, neutrophil chemoattractant, but such changes were not observed in wild type mice. Exposure to ZnO-NPs did not dose-dependently increase mRNA level of Nrf2-dependent antioxidant enzymes both in Nrf2−/− mice and wild type mice. Conclusion: Pharyngeal aspiration of ZnO-NPs induced infiltration of inflammatory cells in the lung of mice, but minimally induced Nrf2-dependent antioxidant enzymes. The results suggest that Nrf2 play a role in negative regulation on ZnO-NP exposure-induced neutrophil migration, but does not demonstrate that the regulation is through suppression of oxidative stress. Keywords: Oxidative stress, Pulmonary inflammation, Nrf2, Zinc oxide nanoparticles
Introduction Engineered nanomaterials (ENMs) with their unique properties currently form a substantial part of many important industrial sectors, consumer products, as well as medicine [1]. Metal-based nanomaterials constitute a major category of ENMs and among them zinc oxide has received great attention and is one of * Correspondence: [email protected] 4 Department of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan Full list of author information is available at the end of the article
the most commonly used nanomaterials due to its unique physical and chemical properties [2]. Zinc oxide nanoparticles (ZnO-
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