ABSTRACT
Introduction
Hyperoxic lung injury is a condition that can occur in patients in need of supplemental oxygen, such as premature infants with bronchopulmonary dysplasia or adults with acute respiratory distress syndrome. Cytochrome P450 (CYP) enzymes play critical roles in the metabolism of endogenous and exogenous compounds.
Areas covered
Through their complex pathways, some subfamilies of these enzymes may contribute to or protect against hyperoxic lung injury. Oxidative stress from reactive oxygen species (ROS) production is most likely a major contributor of hyperoxic lung injury. CYP1A enzymes have been shown to protect against hyperoxic lung injury while CYP1B enzymes seem to contribute to it. CYP2J2 enzymes help protect against hyperoxic lung injury by triggering EET production, thereby, increasing antioxidant enzymes. The metabolism of arachidonic acid to ω-terminal hydroxyeicosatetraenoic acid (20-HETEs) by CYP4A and CYP4F enzymes could impact hyperoxic lung injury via the vasodilating effects of 20-HETE. CYP2E1 and CYP2A enzymes may contribute to the oxidative stress in the lungs caused by ethanol- and nicotine-metabolism, respectively.
Expert opinion
Overall, the CYP enzymes, depending upon the isoform, play a contributory or protective role in hyperoxic lung injury, and are, therefore, ideal candidates for developing drugs that can treat oxygen-mediated lung injury.
Article highlights
CYP1A enzymes located in both the lungs and liver protect against hyperoxic lung injury (HLI) by metabolizing oxidative stress-contributing lipid peroxide products.
CYP1B1 enzymes alter DNA pathways under hyperoxic conditions, contributing to DNA adduct formation and lung injury.
CYP2E1 and CYP2A enzymes can contribute to HLI when chronic ethanol and nicotine metabolism, respectively, occur and high amounts of reactive oxygen species (ROS) are released.
CYP2J2 enzymes increase epoxyeicosatrienoic acid (EET) production, which reduces oxidative stress and HLI through vascular tone regulation and stimulation of antioxidant enzyme production.
CYP4A and CYP4F enzymes may impact HLI from production of ω-terminal hydroxyeicosatetraenoic acids (20-HETEs) but require further research.
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Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.