Advances and Answers in Pediatric Health
ACETAMINOPHEN-EXPOSED AIRWAY
Dead cells
Figure 2
Finally, the team used a preclinical model to mimic exposures early in lung development. The team found that the neonatal liver was resistant to acetaminophen exposures that typically cause liver injury in adults. However, the developing lung demonstrated both metabolic and structural changes. The team continues to work to understand if these changes impact long-term lung function( 4).
“ What we learned was that the neonatal liver handles these acetaminophen exposures quite well, however, the lung has a unique metabolic and immunologic response not previously appreciated,” Dr. Wright explains.“ We need to know why this is happening, and if it causes any long-term problems.”
His latest study, funded by the NICHD grant, will use preclinical models to examine the impact of perinatal acetaminophen exposures on early lung development. Further, he is working to demonstrate and more clearly understand the mechanisms behind these results to illuminate potential solutions.
“ My hope is we can really understand what these enzymes are doing, why they are being expressed in the developing lung and what this tells us about the metabolic forces that drive lung development, and maybe give us some other therapeutic targets to help these babies that are born preterm,” Dr. Wright says.“ We are working hard to make sure that the medications we use in these high-risk babies are both safe and effective.” •
1. Gouyon, Béatrice et al.“ Characteristics of prescription in 29 Level 3 Neonatal Wards over a 2-year period( 2017-2018). An inventory for future research.” PloS one vol. 14,9 e0222667. 19 Sep. 2019, doi: 10.1371 / journal. pone. 0222667
2. Sandoval, Jeryl et al.“ Toxic Acetaminophen Exposure Induces Distal Lung ER Stress, Proinflammatory Signaling, and Emphysematous Changes in the Adult Murine Lung.” Oxidative medicine and cellular longevity vol. 2019 7595126. 28 Nov. 2019, doi: 10.1155 / 2019 / 7595126
3. Dobrinskikh, Evgenia et al.“ Pulmonary implications of acetaminophen exposures independent of hepatic toxicity.” American journal of physiology. Lung cellular and molecular physiology vol. 321,5( 2021): L941-L953. doi: 10.1152 / ajplung. 00234.2021
4. Dobrinskikh, Evgenia et al.“ The developing murine lung is susceptible to acetaminophen toxicity.” American journal of physiology. Lung cellular and molecular physiology vol. 320,5( 2021): L969-L978. doi: 10.1152 / ajplung. 00072.2021
CLYDE WRIGHT, MD
Neonatologist, Children’ s Hospital Colorado
Associate professor, Pediatrics-Neonatology, University of Colorado School of Medicine
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