The triterpenoid CDDO-imidazolide protects against zinc oxide nanoparticle-induced acute lung inflammation in mice
摘要：Zinc oxide nanoparticles（Zn ONPs） are widely used worldwide. Human inhalation exposure to Zn ONPs induces acute lung inflammation（ALI）, however, the preventive and therapeutic target for pulmonary toxicity of Zn ONPs is limited. CDDO-imidazolide（CDDO-Im） is a synthetic triterpenoids,which againsts oxidative stress and inflammation through increasing the transcriptional activity of NRF2.To explore whether CDDO-Im confers protective effects on Zn ONPs-induced ALI. Mice were exposed to20 μg Zn ONPs on day（0） by intratracheal instillation（IT）, administrated with CDDO-Im(2 mg · kg-1)on day（-1 and 1） intraperitoneally and sacrificed on day 3. CDDO-Im significantly de-creased the number of macrophages and concentrations of total protein in bronchoalveolar lavage flu-id, inhibited expression of lung proinflammatory cytokines including Il-6 and Il-8 in ZnONPs+CDDO-Im group compared with Zn ONPs group. Lung pathology showed ameliorated infiltration of inflammatory cells and interstitial thickening, and reduced number of F4/80-and Ly6 g-positive cells after CDDO-Im intervention. Treatment with CDDO-Im upregulated protein levels of NRF2 and its downstream genes（GCLC, GCLM and NQO1）. Collectively, these results suggest that CDDO-Im acts against pulmonary toxicity caused by nanoparticles, and it may serve as a potential pharmacologic strategy to prevent and treat nanoparticle-induced ALI.