ArticleDrug metabolism and disposition: the biological fate of chemicals2014
Essential role of the cytochrome P450 enzyme CYP2A5 in olfactory mucosal toxicity of naphthalene.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
12 citing papers in PubMed, 26 citations in OpenAlex.
- Naphthalene-DNA Adduct Formation in a Lung Airway Explant Model: The Role of Bioactivation and Naphthalene Metabolites.Chemical research in toxicology · 2026Article
- Naphthalene: MAK Value Documentation, addendum - Translation of the German version from 2022.The MAK collection for occupational health and safety · 2025Article
- Using nanotechnology to deliver biomolecules from nose to brain - peptides, proteins, monoclonal antibodies and RNA.Drug delivery and translational research · 2022Article
- Assessing cytochrome P450 function using genetically engineered mouse models.Advances in pharmacology (San Diego, Calif.) · 2022Review
- Health Effects of Naphthalene Exposure: A Systematic Evidence Map and Analysis of Potential Considerations for Dose-Response Evaluation.Environmental health perspectives · 2021Article
- Contribution of Pulmonary CYP-mediated Bioactivation of Naphthalene to Airway Epithelial Injury in the Lung.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Toxicokinetic Interaction between Hepatic Disposition and Pulmonary Bioactivation of Inhaled Naphthalene Studied UsingDrug metabolism and disposition: the biological fate of chemicals · 2019Article
- ATP and Odor Mixture Activate TRPM5-Expressing Microvillous Cells and Potentially Induce Acetylcholine Release to Enhance Supporting Cell Endocytosis in Mouse Main Olfactory Epithelium.Frontiers in cellular neuroscience · 2018Article
- Impact of hepatic P450-mediated biotransformation on the disposition and respiratory tract toxicity of inhaled naphthalene.Toxicology and applied pharmacology · 2017Article
- Human CYP2A13 and CYP2F1 Mediate Naphthalene Toxicity in the Lung and Nasal Mucosa of CYP2A13/2F1-Humanized Mice.Environmental health perspectives · 2017Article
- Structure-Function Studies of Naphthalene, Phenanthrene, Biphenyl, and Their Derivatives in Interaction with and Oxidation by Cytochromes P450 2A13 and 2A6.Chemical research in toxicology · 2016Article
- Hypothesis-based weight-of-evidence evaluation and risk assessment for naphthalene carcinogenesis.Critical reviews in toxicology · 2016Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Naphthalene (NA), a ubiquitous environmental pollutant that can cause pulmonary and nasal toxicity in laboratory animals, requires cytochrome P450 (P450)-mediated metabolic activation to cause toxicity. Our recent study using a Cyp2f2-null mouse showed that CYP2F2 plays an essential role in NA-induced lung toxicity, but not in NA-induced nasal toxicity. The aim of this study was to determine whether mouse CYP2A5, abundantly expressed in nasal olfactory mucosa (OM) and the liver, but less in the lung, plays a major role in the bioactivation and toxicity of NA in the OM. We found, by comparing Cyp2a5-null and wild-type (WT) mice, that the loss of CYP2A5 expression led to substantial decreases in rates of NA metabolic activation by OM microsomes. The loss of CYP2A5 did not cause changes in systemic clearance of NA (at 200 mg/kg, i.p.). However, the Cyp2a5-null mice were much more resistant than were WT mice to NA-induced nasal toxicity (although not lung toxicity), when examined at 24 hours after NA dosing (at 200 mg/kg, i.p.), or to NA-induced depletion of total nonprotein sulfhydryl in the OM (although not in the lung), examined at 2 hours after dosing. Thus, mouse CYP2A5 plays an essential role in the bioactivation and toxicity of NA in the OM, but not in the lung. Our findings further illustrate the tissue-specific nature of the role of individual P450 enzymes in xenobiotic toxicity, and provide the basis for a more reliable assessment of the potential risks of NA nasal toxicity in humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.