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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