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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- Journal Article
- Research Support
- Non-U.S. Gov't
- Review
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
Researcher Affiliations
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
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