Exposure of neonatal mice to bromine impairs their alveolar development and lung function.

Academic Article

Abstract

  • The halogen bromine (Br2) is used extensively in industry and stored and transported in large quantities. Its accidental or malicious release into the atmosphere has resulted in significant casualties. The pathophysiology of Br2-induced lung injury has been studied in adult animals, but the consequences of Br2 exposure to the developing lung are completely unknown. We exposed neonatal mouse littermates on postnatal day 3 (P3) to either Br2 at 400 ppm for 30 min (400/30), to Br2 at 600 ppm for 30 min (600/30), or to room air, then returned them to their dams and observed until P14. Mice exposed to Br2 had decreased survival (S) and had decreased weight (W) at P14 in the 400/30 group (S = 63.5%, W = 6.67 ± 0.08) and in the 600/30 group (S = 36.1%, W = 5.13 ± 0.67) as compared with air breathing mice (S = 100%, W = 7.96 ± 0.30). Alveolar development was impaired, as evidenced by increased mean linear intercept at P14. At P14, Br2 exposed mice also exhibited a decrease of arterial partial pressure of oxygen, decreased quasi-static lung compliance, as well as increased alpha smooth muscle actin mRNA and protein and increased mRNA for IL-1β, IL-6, CXCL1, and TNFα. Global gene expression, evaluated by RNA sequencing and Ingenuity Pathway Analysis, revealed persistent abnormalities in gene expression profiles at P14 involving pathways of "formation of lung" and "pulmonary development." The data indicate that Br2 inhalation injury early in life results in severe lung developmental consequences, wherein persistent inflammation and global altered developmental gene expression are likely mechanistic contributors.
  • Keywords

  • bronchopulmonary dysplasia, halogen, lung development, lung injury, Animals, Animals, Newborn, Bromine, Bronchopulmonary Dysplasia, Female, Gene Expression Regulation, Lung Injury, Mice, Mice, Inbred C57BL, Pregnancy, Prenatal Exposure Delayed Effects, Pulmonary Alveoli
  • Digital Object Identifier (doi)

    Author List

  • Jilling T; Ren C; Yee A; Aggarwal S; Halloran B; Ambalavanan N; Matalon S
  • Start Page

  • L137
  • End Page

  • L143
  • Volume

  • 314
  • Issue

  • 1