Role of Nrf2 in inflammatory response in lung of mice exposed to zinc oxide nanoparticles

Radwa Sehsah, Wenting Wu, Sahoko Ichihara, Naozumi Hashimoto, Yoshinori Hasegawa, Cai Zong, Ken Itoh, Masayuki Yamamoto, Ahmed Ali Elsayed, Soheir El-Bestar, Emily Kamel, Gaku Ichihara

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


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.

Original languageEnglish
Article number47
JournalParticle and Fibre Toxicology
Issue number1
Publication statusPublished - 2019 Dec 16


  • Nrf2
  • Oxidative stress
  • Pulmonary inflammation
  • Zinc oxide nanoparticles


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