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The developing murine lung is susceptible to acetaminophen toxicity
Evgenia Dobrinskikh1,2, Laura G Sherlock1, David J Orlicky3
1Section of Neonatology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.
Summary
Toxic acetaminophen (n-acetyl-p-aminophenol, APAP) exposure injures the developing neonatal lung, even without liver damage. This study reveals previously unrecognized pulmonary toxicity and metabolic shifts, emphasizing the need for further research.
Area of Science:
- Neonatal toxicology
- Pulmonary medicine
- Developmental biology
Background:
- Acetaminophen (APAP) use is increasing in neonatal intensive care units.
- While APAP hepatotoxicity is rare in neonates, other organ toxicities are possible.
- APAP-induced lung injury is known in adults, but its effect on developing lungs is unclear.
Purpose of the Study:
- To investigate whether toxic APAP exposure causes lung injury in developing neonatal lungs.
- To identify the mechanisms of APAP-induced lung injury in neonates.
Main Methods:
- Neonatal mice (PN7) received a hepatotoxic dose of APAP (280 mg/kg).
- Lung injury, gene expression (Cyp2e1, antioxidant response, cytokines, chemokines), enzyme activity, and pulmonary metabolism were assessed.
Main Results:
- Toxic APAP exposure induced significant lung injury without observable liver toxicity.
- Increased pulmonary Cyp2e1 expression, antioxidant gene response, and proinflammatory markers were observed.
- Pulmonary metabolism shifted from glycolysis to oxidative phosphorylation, suggesting increased mitochondrial workload and potential toxicity.
Conclusions:
- Toxic APAP exposure can cause significant lung injury in the developing neonatal lung.
- This injury involves altered gene expression, metabolic shifts, and increased mitochondrial workload.
- Neonatal APAP exposure requires evaluation beyond potential liver effects, considering acute and long-term pulmonary implications.
