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Equine veterinary journal1984; 16(3); 163-175; doi: 10.1111/j.2042-3306.1984.tb01893.x

The acute inflammatory process, arachidonic acid metabolism and the mode of action of anti-inflammatory drugs.

Abstract: Arachidonic acid is a polyunsaturated fatty acid covalently bound in esterified form in the cell membranes of most body cells. Following irritation or injury, arachidonic acid is released and oxygenated by enzyme systems leading to the formation of an important group of inflammatory mediators, the eicosanoids. It is now recognised that eicosanoid release is fundamental to the inflammatory process. For example, the prostaglandins and other prostanoids, products of the cyclooxygenase enzyme pathway, have potent inflammatory properties and prostaglandin E2 is readily detectable in equine acute inflammatory exudates. The administration of nonsteroidal anti-inflammatory drugs results in inhibition of prostaglandin synthesis and this explains the mode of action of agents such as phenylbutazone and flunixin. Lipoxygenase enzymes metabolise arachidonic acid to a group of noncyclised eicosanoids, the leukotrienes, some of which are also important inflammatory mediators. They are probably of particular importance in leucocyte-mediated aspects of chronic inflammation. Currently available non-steroidal anti-inflammatory drugs, however, do not inhibit lipoxygenase activity. In the light of recent evidence, the inflammatory process is re-examined and the important emerging roles of both cyclo-oxygenase and lipoxygenase derived eicosanoids are explored. The mode of action of current and future anti-inflammatory drugs offered to the equine clinician can be explained by their interference with arachidonic acid metabolism.
Publication Date: 1984-05-01 PubMed ID: 6428879DOI: 10.1111/j.2042-3306.1984.tb01893.xGoogle Scholar: Lookup
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Summary

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The research article discusses the role of arachidonic acid in the inflammatory process and how anti-inflammatory drugs combat inflammation by interfering with arachidonic acid metabolism.

Role of Arachidonic Acid in Inflammation

  • Arachidonic acid is a type of fatty acid that is present in the cell membranes of most body cells. When cells are injured or irritated, arachidonic acid is released.
  • The released arachidonic acid is acted upon by enzyme systems that oxygenate it, leading to the formation of a group of inflammatory mediators known as eicosanoids.
  • The release of eicosanoids is fundamental to the inflammatory process. For instance, prostaglandins and other prostanoids, products of the cyclooxygenase enzyme pathway, have potent inflammatory properties. One such product, prostaglandin E2, is often found in equine acute inflammatory exudates.

Anti-Inflammatory Drugs and Their Mode of Action

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the process of prostaglandin synthesis, which is essential in the inflammation process. This explains the mode of action of anti-inflammatory agents such as phenylbutazone and flunixin.
  • Arachidonic acid is also metabolized by lipoxygenase enzymes to form leukotrienes, another group of eicosanoids. Certain leukotrienes are also important inflammatory mediators and play a key role in leukocyte-mediated aspects of chronic inflammation.
  • However, the currently available NSAIDs do not inhibit lipoxygenase activity, hence they do not affect the formation of leukotrienes.

Understanding of Inflammation Process and Anti-Inflammatory Drugs

  • The paper reassesses the understanding of inflammation based on recent evidence, with a focus on the role of eicosanoids derived from both cyclooxygenase and lipoxygenase pathways.
  • By understanding the role of arachidonic acid metabolism in inflammation, we can better grasp the mode of action of current and future anti-inflammatory drugs. Such drugs work by interrupting arachidonic acid metabolism, thus subduing inflammation.

Cite This Article

APA
Higgins AJ, Lees P. (1984). The acute inflammatory process, arachidonic acid metabolism and the mode of action of anti-inflammatory drugs. Equine Vet J, 16(3), 163-175. https://doi.org/10.1111/j.2042-3306.1984.tb01893.x

Publication

ISSN: 0425-1644
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 16
Issue: 3
Pages: 163-175

Researcher Affiliations

Higgins, A J
    Lees, P

      MeSH Terms

      • Adrenal Cortex Hormones / pharmacology
      • Animals
      • Anti-Inflammatory Agents / pharmacology
      • Anti-Inflammatory Agents / therapeutic use
      • Arachidonic Acid
      • Arachidonic Acids / metabolism
      • Blood Coagulation
      • Chemotaxis
      • Complement System Proteins / physiology
      • Cyclooxygenase Inhibitors
      • Histamine / physiology
      • Horse Diseases / drug therapy
      • Horse Diseases / metabolism
      • Horse Diseases / physiopathology
      • Horses
      • Inflammation / drug therapy
      • Inflammation / metabolism
      • Inflammation / veterinary
      • Kinins / physiology
      • Lipoxygenase / metabolism
      • Lipoxygenase Inhibitors
      • Phenylbutazone / pharmacology
      • Prostaglandin-Endoperoxide Synthases / metabolism
      • Prostaglandins / biosynthesis
      • Serotonin / physiology

      References

      This article includes 143 references

      Citations

      This article has been cited 36 times.
      1. Conceição JDS, Khatlab AS, Gasparino E, Santana TP, Carvalho AS, Batista MVA, Filho MS, Guimaraes SEF, Vieira JS, Vesco APD. Combined effects of incubation temperature and lipopolysaccharide exposure on immune response modulation in the quail gut. Poult Sci 2026 Jan 13;105(4):106418.
        doi: 10.1016/j.psj.2026.106418pubmed: 41616531google scholar: lookup
      2. Ahrens AP, Dias R, Hyötyläinen T, Orešič M, Triplett EW, Ludvigsson J. The inflammatory path toward type 1 diabetes begins during pregnancy. Nat Commun 2026 Jan 7;17(1):979.
        doi: 10.1038/s41467-025-67712-6pubmed: 41501048google scholar: lookup
      3. Lan C, Ren W, Wu A, Yu B, He J, Luo Y, Chen D. Prevotella copri alleviates diarrhea in weaning piglets through gut microbiota modulation and arachidonic acid-AHR-NRF2 pathway activation. J Anim Sci Biotechnol 2025 Nov 20;16(1):154.
        doi: 10.1186/s40104-025-01273-ypubmed: 41261441google scholar: lookup
      4. Terada A, Fujimoto K, Kise K, Fujiwara K, Uchino E, Mizuma Y, Nishioku Y, Takahashi K, Itoh K, Mikami T, Murashita K, Nakaji S, Fujita Y, Okuno Y, Tamada Y. Network analysis reveals causal relationships among individual background risk factors leading to influenza susceptibility. Sci Rep 2025 Aug 21;15(1):30721.
        doi: 10.1038/s41598-025-15131-4pubmed: 40841724google scholar: lookup
      5. Fidan BB, Koç E, Özotuk EÇ, Kaplan O, Çelebier M, Korkusuz F. Do Preparation Techniques Transform the Metabolite Profile of Platelet-Rich Plasma?. Bioengineering (Basel) 2025 Jul 17;12(7).
      6. Mahrous RS, Fathy H, Ghareeb DA, Abdel-Hamid AS, Ibrahim RS. Network pharmacology and UPLC/MS/MS metabolic profiling unveil the anti-inflammatory potential of Trifolium alexandrinum. NPJ Sci Food 2025 Jun 14;9(1):102.
        doi: 10.1038/s41538-025-00459-ypubmed: 40517168google scholar: lookup
      7. Davico B, Martin M, Condori AI, Chiappe EL, Gaete L, Tetzlaff WF, Yanez A, Osta V, Sáez MS, Bava A, Godoy MF, Palenque P, Ballerini MG, Trifone L, Rosso LG, Feliu MS, Brites F. Fatty Acids in Childhood Obesity: A Link Between Nutrition, Metabolic Alterations and Cardiovascular Risk. J Lipid Atheroscler 2025 May;14(2):200-218.
        doi: 10.12997/jla.2025.14.2.200pubmed: 40492180google scholar: lookup
      8. Hansen CE, Konings J, Toth G, Chornyi S, Karsten M, van Het Hof B, van der Pol SMA, Beekhuis-Hoekstra SD, Kok N, Fung WK, Dijksman NS, Baron W, Witte ME, Lanekoff I, de Vries HE, Kooij G. Spatial mapping of the AA-PGE(2)-EP axis in multiple sclerosis lesions. Acta Neuropathol 2025 Apr 29;149(1):39.
        doi: 10.1007/s00401-025-02878-3pubmed: 40299057google scholar: lookup
      9. Foong YH, Caldwell B, Thorvaldsen JL, Krapp C, Mesaros CA, Zhou W, Kohli RM, Bartolomei MS. TET1 displays catalytic and non-catalytic functions in the adult mouse cortex. Epigenetics 2024 Dec;19(1):2374979.
        doi: 10.1080/15592294.2024.2374979pubmed: 38970823google scholar: lookup
      10. Liu M, Du X, Chen H, Bai C, Lan L. Systemic investigation of di-isobutyl phthalate (DIBP) exposure in the risk of cardiovascular via influencing the gut microbiota arachidonic acid metabolism in obese mice model. Regen Ther 2024 Dec;27:290-300.
        doi: 10.1016/j.reth.2024.03.024pubmed: 38638558google scholar: lookup
      11. Ismaila MS, Sanusi KO, Iliyasu U, Imam MU, Georges K, Sundaram V, Jones KR. Antioxidant and Anti-Inflammatory Properties of Quail Yolk Oil via Upregulation of Superoxide Dismutase 1 and Catalase Genes and Downregulation of EIGER and Unpaired 2 Genes in a D. melanogaster Model. Antioxidants (Basel) 2024 Jan 5;13(1).
        doi: 10.3390/antiox13010075pubmed: 38247499google scholar: lookup
      12. Phat NK, Tien NTN, Anh NK, Yen NTH, Lee YA, Trinh HKT, Le KM, Ahn S, Cho YS, Park S, Kim DH, Long NP, Shin JG. Alterations of lipid-related genes during anti-tuberculosis treatment: insights into host immune responses and potential transcriptional biomarkers. Front Immunol 2023;14:1210372.
        doi: 10.3389/fimmu.2023.1210372pubmed: 38022579google scholar: lookup
      13. Li W, Zhang C, Aramaki S, Xu L, Tsuge S, Sakamoto T, Mamun MA, Islam A, Hayakawa T, Takanashi Y, Dubail M, Konishi K, Sato T, Kahyo T, Fouillade C, Nakamura K, Setou M. Lipid Polyunsaturated Fatty Acid Chains in Mouse Kidneys Were Increased within 5 min of a Single High Dose Whole Body Irradiation. Int J Mol Sci 2023 Aug 4;24(15).
        doi: 10.3390/ijms241512439pubmed: 37569813google scholar: lookup
      14. Kumar Rokkam S, Mas-Rosario JA, Joshi BP, Joshi M, Choudhury AR, Kar S, Golakoti NR, Farkas ME. Diarylidene-N-Methyl-4-Piperidones and Spirobibenzopyrans as Antioxidant and Anti-Inflammatory Agents. Chem Biodivers 2023 Sep;20(9):e202300822.
        doi: 10.1002/cbdv.202300822pubmed: 37537138google scholar: lookup
      15. Gartling G, Nakamura R, Sayce L, Kimball EE, Wilson A, Schneeberger S, Zimmerman Z, Garabedian MJ, Branski RC, Rousseau B. Acute Effects of Systemic Glucocorticoids on the Vocal Folds in a Pre-Clinical Model. Ann Otol Rhinol Laryngol 2024 Jan;133(1):87-96.
        doi: 10.1177/00034894231188571pubmed: 37497827google scholar: lookup
      16. Xue Q, Liu X, Zhu R, Zhang T, Dong X, Jiang Y. Comprehensive analysis of transcriptomics and metabolomics to understand chronic ethanol induced murine cardiotoxicity. Mol Cell Biochem 2023 Jun;478(6):1345-1359.
        doi: 10.1007/s11010-022-04592-0pubmed: 36309883google scholar: lookup
      17. Galindez SM, Keightley A, Koulen P. Differential distribution of steroid hormone signaling networks in the human choroid-retinal pigment epithelial complex. BMC Ophthalmol 2022 Oct 20;22(1):406.
        doi: 10.1186/s12886-022-02585-7pubmed: 36266625google scholar: lookup
      18. Sun M, Zhao H, Liu Y, Ma Y, Tian Z, Wang H, Wei S, Guo Q, Gu Z, Jiang H. Deciphering the pharmacological mechanisms of Chaenomeles Fructus against rheumatoid arthritis by integrating network pharmacology and experimental validation. Food Sci Nutr 2022 Oct;10(10):3380-3394.
        doi: 10.1002/fsn3.2938pubmed: 36249962google scholar: lookup
      19. Li J, Sun M, Cui X, Li C. Protective Effects of Flavonoids against Alzheimer's Disease: Pathological Hypothesis, Potential Targets, and Structure-Activity Relationship. Int J Mol Sci 2022 Sep 2;23(17).
        doi: 10.3390/ijms231710020pubmed: 36077418google scholar: lookup
      20. Needham H, Torpey G, Flores CC, Davis CJ, Vanderheyden WM, Gerstner JR. A Dichotomous Role for FABP7 in Sleep and Alzheimer's Disease Pathogenesis: A Hypothesis. Front Neurosci 2022;16:798994.
        doi: 10.3389/fnins.2022.798994pubmed: 35844236google scholar: lookup
      21. Metwally AA, Zhang T, Wu S, Kellogg R, Zhou W, Contrepois K, Tang H, Snyder M. Robust identification of temporal biomarkers in longitudinal omics studies. Bioinformatics 2022 Aug 2;38(15):3802-3811.
      22. Jeong SY, Choi WS, Kwon OS, Lee JS, Son SY, Lee CH, Lee S, Song JY, Lee YJ, Lee JY. Extract of Pinus densiflora needles suppresses acute inflammation by regulating inflammatory mediators in RAW264.7 macrophages and mice. Pharm Biol 2022 Dec;60(1):1148-1159.
        doi: 10.1080/13880209.2022.2079679pubmed: 35695008google scholar: lookup
      23. Hatton SL, Pandey MK. Fat and Protein Combat Triggers Immunological Weapons of Innate and Adaptive Immune Systems to Launch Neuroinflammation in Parkinson's Disease. Int J Mol Sci 2022 Jan 19;23(3).
        doi: 10.3390/ijms23031089pubmed: 35163013google scholar: lookup
      24. Rahman MM, Vadrev SM, Magana-Mora A, Levman J, Soufan O. A novel graph mining approach to predict and evaluate food-drug interactions. Sci Rep 2022 Jan 20;12(1):1061.
        doi: 10.1038/s41598-022-05132-ypubmed: 35058561google scholar: lookup
      25. Li Z, Ma D, Peng L, Li Y, Liao Z, Yu T. Compatibility of Achyranthes bidentata components in reducing inflammatory response through Arachidonic acid pathway for treatment of Osteoarthritis. Bioengineered 2022 Jan;13(1):1746-1757.
        doi: 10.1080/21655979.2021.2020394pubmed: 35001833google scholar: lookup
      26. Kotlyarov S, Kotlyarova A. Anti-Inflammatory Function of Fatty Acids and Involvement of Their Metabolites in the Resolution of Inflammation in Chronic Obstructive Pulmonary Disease. Int J Mol Sci 2021 Nov 26;22(23).
        doi: 10.3390/ijms222312803pubmed: 34884621google scholar: lookup
      27. Dopkins N, Neameh WH, Hall A, Lai Y, Rutkovsky A, Gandy AO, Lu K, Nagarkatti PS, Nagarkatti M. Effects of Acute 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Exposure on the Circulating and Cecal Metabolome Profile. Int J Mol Sci 2021 Oct 30;22(21).
        doi: 10.3390/ijms222111801pubmed: 34769237google scholar: lookup
      28. Bai S, Xie J, Bai H, Tian T, Zou T, Chen JJ. Gut Microbiota-Derived Inflammation-Related Serum Metabolites as Potential Biomarkers for Major Depressive Disorder. J Inflamm Res 2021;14:3755-3766.
        doi: 10.2147/JIR.S324922pubmed: 34393496google scholar: lookup
      29. Kulkarni A, Nadler JL, Mirmira RG, Casimiro I. Regulation of Tissue Inflammation by 12-Lipoxygenases. Biomolecules 2021 May 11;11(5).
        doi: 10.3390/biom11050717pubmed: 34064822google scholar: lookup
      30. Eveque-Mourroux MR, Emans PJ, Boonen A, Claes BSR, Bouwman FG, Heeren RMA, Cillero-Pastor B. Heterogeneity of Lipid and Protein Cartilage Profiles Associated with Human Osteoarthritis with or without Type 2 Diabetes Mellitus. J Proteome Res 2021 May 7;20(5):2973-2982.
        doi: 10.1021/acs.jproteome.1c00186pubmed: 33866785google scholar: lookup
      31. Chhonker YS, Kanvinde S, Ahmad R, Singh AB, Oupický D, Murry DJ. Simultaneous Quantitation of Lipid Biomarkers for Inflammatory Bowel Disease Using LC-MS/MS. Metabolites 2021 Feb 12;11(2).
        doi: 10.3390/metabo11020106pubmed: 33673198google scholar: lookup
      32. Yakah W, Singh P, Perides G, Brown J, Freedman SD, Martin CR. Developmental Accretion of Docosahexaenoic Acid Is Independent of Fatty Acid Transporter Expression in Brain and Lung Tissues of C57BL/6 and Fat1 Mice. J Nutr 2019 Oct 1;149(10):1724-1731.
        doi: 10.1093/jn/nxz074pubmed: 31179494google scholar: lookup
      33. Kask K, Malmgren L, Odensvik K. Prostaglandin F2 alpha metabolite levels following an embryo transfer procedure in the mare. Acta Vet Scand 1995;36(1):145-7.
        doi: 10.1186/BF03547711pubmed: 7572452google scholar: lookup
      34. Margolis JH, Bottoms GD, Fessler JF. The efficacy of dexamethasone and flunixin meglumine in treating endotoxin-induced changes in calves. Vet Res Commun 1987;11(5):479-91.
        doi: 10.1007/BF00380630pubmed: 3445446google scholar: lookup
      35. Carrick JB, Papich MG, Middleton DM, Naylor JM, Townsend HG. Clinical and pathological effects of flunixin meglumine administration to neonatal foals. Can J Vet Res 1989 Apr;53(2):195-201.
        pubmed: 2713784
      36. Persson K. Microcirculation in the bovine teat skin, measured by laser Doppler flowmetry. Acta Vet Scand 1991;32(1):131-3.
        doi: 10.1186/BF03547005pubmed: 1950846google scholar: lookup