Abstract
BackgroundZinc 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.MethodsTwenty-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.ResultsExposure 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.ConclusionPharyngeal 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.
Highlights
Engineered nanomaterials (ENMs) with their unique properties currently form a substantial part of many important industrial sectors, consumer products, as well as medicine [1]
The present study investigated the role of nuclear factor-erythroid 2-related factor (Nrf2) pathway and the potential role of oxidative stress in Zinc oxide nanoparticles (ZnO-NPs)-induced pulmonary inflammation, using Nrf2−/− mice model
Changes in body and lung weights Following pharyngeal aspiration, body weight decreased in all mice, which recovered rapidly from the third to fourth day post-exposure in both the control and 10 μg ZnO-NP groups of both genotypes
Summary
Engineered nanomaterials (ENMs) with their unique properties currently form a substantial part of many important industrial sectors, consumer products, as well as medicine [1]. While many in vitro and in vivo studies provided strong evidence for the production of reactive oxygen species (ROS) and oxidative stress as the main mechanism of ZnO-NPs-induced cytotoxicity [14,15,16,17], Song et al [18] stated that ROS was not necessarily the main contributing factor of ZnO-NPs-related cytotoxicity and Shen et al [19] suggested that ROS may be the result of cytotoxicity rather than the cause. 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. The mRNA levels of Nrf2-dependent antioxidant enzymes and inflammatory cytokines in lung tissue were measured
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