ORIGINAL RESEARCH article
Front. Public Health
Sec. Environmental Health and Exposome
Volume 13 - 2025 | doi: 10.3389/fpubh.2025.1531134
This article is part of the Research TopicUnderstanding EPFRs: Mechanisms, Health Effects, and Policy ImplicationsView all articles
Environmentally Persistent Free Radicals lead to selective inhibition of CYP1 monooxygenase activities, and increased production of reactive oxygen species by reaction uncoupling
Provisionally accepted
- LSU Health Sciences Center New Orleans, Louisiana State University, New Orleans, United States
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This study focuses on the effect of Environmentally Persistent Free Radicals (EPFRs) on the P450 enzymes of the CYP1 family. EPFRs are a component of particulate pollutants, that are stable in the environment, but can generate free radicals, leading to oxidative stress and subsequent toxicity of the respiratory, cardiovascular, and immune systems once they enter an organism. The results show differences in the ability of EPFRs to inhibit CYP1-dependent substrate metabolism, with CYP1B1 being inhibited to the greatest extent. There also were differences in the ability of EPFRs to disrupt the POR•CYP1 complex, with CYP1B1 being the only form where EPFRs disrupted POR•CYP1B1 complex formation. Despite the inhibition of substrate metabolism, each CYP1 enzyme, when reconstituted with NADPH-cytochrome P450 reductase (POR) was able to synergistically stimulate the generation of reactive oxygen (ROS) in the presence of particulate matter. Interestingly, both POR and the CYP1 enzymes were able to stimulate ROS generation, even when in partial reconstituted systems where only one of the proteins was present. However, when both POR and CYP1 were combined in a complete reconstituted system, ROS generation was synergistically stimulated.
Keywords: Environmentally persistent free radicals, cytochrome P450, CYP1A1, CYP1A2, CYP1B1, Reactive Oxygen Species, enzyme inhibition, protein-protein interactions
Received: 09 Dec 2024; Accepted: 14 May 2025.
Copyright: © 2025 Connick, Stepter, Cawley, Eyer and Backes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wayne Louis Backes, LSU Health Sciences Center New Orleans, Louisiana State University, New Orleans, United States
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