Deferasirox, an iron-chelating agent, alleviates acute lung inflammation by inhibiting neutrophil activation and extracellular trap formation

Deferasirox, an iron-chelating agent, alleviates acute lung inflammation by inhibiting neutrophil activation and extracellular trap formation: Journal of International Medical Research, Volume 48, Issue 9, September 2020.

ObjectiveReactive oxygen species (ROS) production by neutrophils induces pulmonary endothelial cell damage and results in acute lung injury (ALI). We previously reported that deferasirox (DFS), an iron-chelating agent, inhibits the ROS production and neutrophil extracellular trap (NET) formation induced by phorbol myristate acetate and formylmethionylleucylphenylalanine in vitro. In the present study, we investigated the effects of DFS in vivo using a mouse model of lipopolysaccharide (LPS)-induced ALI.MethodsAfter DFS administration for 7 days, ALI was induced in mice by LPS via intratracheal administration.ResultsLPS treatment induced neutrophil invasion in the lung tissues, along with NET formation and a significant increase in the quantity of double-stranded DNA in the bronchoalveolar lavage fluid, while pre-administered DFS inhibited these phenomena. However, alteration of neutrophil morphology in the cytoplasm in terms of shape and vacuolization was not inhibited by the pre-administration of DFS, possibly through ROS production.ConclusionsDFS suppressed neutrophil invasion into lung tissues and reduced the double-stranded DNA content released by the neutrophils. These results suggest that DFS can potentially be used to prevent diseases related to neutrophil activation including ALI, thrombosis, and vascular endothelial dysfunction.