ArticleBritish journal of pharmacology2010
The 5-lipoxygenase inhibitor, zileuton, suppresses prostaglandin biosynthesis by inhibition of arachidonic acid release in macrophages.
Article in British journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 131 citations in OpenAlex.
- Effect of zileuton and celecoxib on urinary LTE4 and PGE-M levels in smokers.Cancer prevention research (Philadelphia, Pa.) · 2013Trial
- Synergistic effects of AgNPs and zileuton on PCOS via ferroptosis and inflammation mitigation.Redox report : communications in free radical research · 2025Article
- Preparation, physicochemical properties, and immunomodulatory activity of glycoproteins from Syngnathoides biaculeatus.Natural products and bioprospecting · 2025Article
- Repeated-Dose Toxicity of Lauric Acid and Its Preventive Effect Against Tracheal Hyper-Responsiveness in Wistar Rats with PossiblePharmaceuticals (Basel, Switzerland) · 2025Article
- Zileuton protects against arachidonic acid/5-lipoxygenase/leukotriene axis-mediated neuroinflammation in experimental traumatic brain injury.Frontiers in pharmacology · 2025Article
- Impact of 5-Lipoxygenase Deficiency on Dopamine-Mediated Behavioral Responses.Neurotoxicity research · 2024Article
- Evaluation of gender differences in the pharmacokinetics of oral zileuton nanocrystalline formulation using a rat model.International journal of pharmaceutics: X · 2024Article
- Effects of some anti-ulcer and anti-inflammatory natural products on cyclooxygenase and lipoxygenase enzymes: insights from in silico analysis.In silico pharmacology · 2024Article
- Hematopoietic 12/15-lipoxygenase activity negatively contributes to fungal-associated allergic asthma.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Eculizumab treatment alters the proteometabolome beyond the inhibition of complement.JCI insight · 2023Article
- Aspirin eugenol ester ameliorates LPS-induced inflammatory responses in RAW264.7 cells and mice.Frontiers in pharmacology · 2023Article
- The role of ferroptosis in intervertebral disc degeneration.Frontiers in cell and developmental biology · 2023Review
- Knock-out of 5-lipoxygenase in overexpressing tumor cells-consequences on gene expression and cellular function.Cancer gene therapy · 2023Article
- The role of oxylipins in NSAID-exacerbated respiratory disease (N-ERD).Advances in pharmacology (San Diego, Calif.) · 2023Article
- Small Airway Disease in Pediatric Asthma: the Who, What, When, Where, Why, and How to Remediate. A Review and Commentary.Clinical reviews in allergy & immunology · 2022Review
- Maternal Inflammation Exaggerates Offspring Susceptibility to Cerebral Ischemia-Reperfusion Injury via the COX-2/PGD2/DPOxidative medicine and cellular longevity · 2022Article
- Identification of a Bromodomain-like Region in 15-Lipoxygenase-1 Explains Its Nuclear Localization.Angewandte Chemie (International ed. in English) · 2021Article
- Modulation of the Primary Astrocyte-Enriched Cultures' Oxylipin Profiles Reduces Neurotoxicity.Metabolites · 2021Article
- An ACE inhibitor reduces bactericidal activity of human neutrophils in vitro and impairs mouse neutrophil activity in vivo.Science translational medicine · 2021Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeZileuton is the only 5-lipoxygenase (5-LOX) inhibitor marketed as a treatment for asthma, and is often utilized as a selective tool to evaluate the role of 5-LOX and leukotrienes. The aim of this study was to investigate the effect of zileuton on prostaglandin (PG) production in vitro and in vivo. EXPERIMENTAL APPROACH: Peritoneal macrophages activated with lipopolysaccharide (LPS)/interferon γ (LPS/IFNγ), J774 macrophages and human whole blood stimulated with LPS were used as in vitro models and rat carrageenan-induced pleurisy as an in vivo model. KEY
resultsZileuton suppressed PG biosynthesis by interference with arachidonic acid (AA) release in macrophages. We found that zileuton significantly reduced PGE2 and 6-keto prostaglandin F1α (PGF1α) levels in activated mouse peritoneal macrophages and in J774 macrophages. This effect was not related to 5-LOX inhibition, because it was also observed in macrophages from 5-LOX knockout mice. Notably, zileuton inhibited PGE2 production in LPS-stimulated human whole blood and suppressed PGE2 and 6-keto PGF1α pleural levels in rat carrageenan-induced pleurisy. Interestingly, zileuton failed to inhibit the activity of microsomal PGE2 synthase1 and of cyclooxygenase (COX)-2 and did not affect COX-2 expression. However, zileuton significantly decreased AA release in macrophages accompanied by inhibition of phospholipase A2 translocation to cellular membranes. CONCLUSIONS AND IMPLICATION: Zileuton inhibited PG production by interfering at the level of AA release. Its mechanism of action, as well as its use as a pharmacological tool, in experimental models of inflammation should be reassessed.
Indexed as
Identifiers
What OpenQuestion holds
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.