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Animal models in leukotriene research: Current insights into complex pathways and therapeutic intervention.

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Title: Animal models in leukotriene research: Current insights into complex pathways and therapeutic intervention.
Authors: Teder T; Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden., Rådmark O; Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden., Haeggström JZ; Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden., Lõhelaid H; Drug Research Program, Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Finland. Electronic address: helike.lohelaid@helsinki.fi.
Source: Pharmacology & therapeutics [Pharmacol Ther] 2025 Dec; Vol. 276, pp. 108944. Date of Electronic Publication: 2025 Oct 27.
Publication Type: Journal Article; Review; Research Support, Non-U.S. Gov't
Language: English
Journal Info: Publisher: Pergamon Press Country of Publication: England NLM ID: 7905840 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-016X (Electronic) Linking ISSN: 01637258 NLM ISO Abbreviation: Pharmacol Ther Subsets: MEDLINE
Imprint Name(s): Original Publication: Oxford, Elmsford, N. Y., Pergamon Press.
MeSH Terms: Leukotrienes*/metabolism , Models, Animal*, Arachidonate 5-Lipoxygenase/metabolism ; Oxylipins/metabolism ; Animals ; Humans ; Disease Models, Animal
Abstract: Oxylipins are oxygenated bioactive lipid mediators formed from different polyunsaturated fatty acids through the bioactions of cyclooxygenases, lipoxygenases and cytochrome P450 enzymes, and participate in many physiological and pathophysiological processes. For example, oxylipins regulate vascular tone, the onset of labor, pain, inflammation, fever and contribute to diseases such as asthma, cancer, arthritis, diabetes, obesity and neurodegenerative disorders. Understanding the mechanisms and cellular components involved in oxylipin biosynthesis is crucial for developing effective therapies that minimize complications and improve disease outcomes. Thus far, various animal models have increased our understanding of oxylipin biosynthesis and regulation in complex biological environments. These models have also facilitated the discovery of novel drug targets and the evaluation of drug safety and efficacy. However, each species used as a model system has its own advantages and limitations. Here we provide an overview of the most relevant and widely used models in lipid mediator research with a focus on 5-lipoxygenase and leukotriene pathway, emphasizing the significance of animal models in advancing our understanding of the complexities of leukotriene biology and its implications for human health.
(Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of competing interest No competing interest.
Contributed Indexing: Keywords: 5-Lipoxygenase; Animal models; Disease mechanisms; Inflammation; Leukotrienes; Oxylipins
Substance Nomenclature: 0 (Leukotrienes)
EC 1.13.11.34 (Arachidonate 5-Lipoxygenase)
0 (Oxylipins)
Entry Date(s): Date Created: 20251029 Date Completed: 20251112 Latest Revision: 20260610
Update Code: 20260610
DOI: 10.1016/j.pharmthera.2025.108944
PMID: 41161355
Database: MEDLINE
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  Data: Animal models in leukotriene research: Current insights into complex pathways and therapeutic intervention.
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  Data: <searchLink fieldCode="AU" term="%22Teder+T%22">Teder T</searchLink>; Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.<br /><searchLink fieldCode="AU" term="%22Rådmark+O%22">Rådmark O</searchLink>; Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.<br /><searchLink fieldCode="AU" term="%22Haeggström+JZ%22">Haeggström JZ</searchLink>; Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.<br /><searchLink fieldCode="AU" term="%22Lõhelaid+H%22">Lõhelaid H</searchLink>; Drug Research Program, Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Finland. Electronic address: helike.lohelaid@helsinki.fi.
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  Data: <i>Original Publication</i>: Oxford, Elmsford, N. Y., Pergamon Press.
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  Data: Oxylipins are oxygenated bioactive lipid mediators formed from different polyunsaturated fatty acids through the bioactions of cyclooxygenases, lipoxygenases and cytochrome P450 enzymes, and participate in many physiological and pathophysiological processes. For example, oxylipins regulate vascular tone, the onset of labor, pain, inflammation, fever and contribute to diseases such as asthma, cancer, arthritis, diabetes, obesity and neurodegenerative disorders. Understanding the mechanisms and cellular components involved in oxylipin biosynthesis is crucial for developing effective therapies that minimize complications and improve disease outcomes. Thus far, various animal models have increased our understanding of oxylipin biosynthesis and regulation in complex biological environments. These models have also facilitated the discovery of novel drug targets and the evaluation of drug safety and efficacy. However, each species used as a model system has its own advantages and limitations. Here we provide an overview of the most relevant and widely used models in lipid mediator research with a focus on 5-lipoxygenase and leukotriene pathway, emphasizing the significance of animal models in advancing our understanding of the complexities of leukotriene biology and its implications for human health.<br /> (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)
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  Data: Declaration of competing interest No competing interest.
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  Data: <i>Keywords: </i>5-Lipoxygenase; Animal models; Disease mechanisms; Inflammation; Leukotrienes; Oxylipins
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  Data: 0 (Leukotrienes)<br />EC 1.13.11.34 (Arachidonate 5-Lipoxygenase)<br />0 (Oxylipins)
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  Data: <i>Date Created: </i>20251029 <i>Date Completed: </i>20251112 <i>Latest Revision: </i>20260610
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  Data: 10.1016/j.pharmthera.2025.108944
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