Abstract
In mammalian cells, eicosanoid biosynthesis is usually initiated by the activation of phospholipase A2 and the release of arachidonic acid (AA) from membrane phospholipids. The AA is subsequently transformed by cyclooxygenase (COX) and lipoxygenase (LO) pathways to prostaglandins, thromboxane and leukotrienes collectively termed eicosanoids. Eicosanoid production is considerably increased during inflammation. Both COX and LO pathways are of particular clinical relevance. The COX pathway is the major target for non-steroidal anti-inflammatory drugs (NSAIDs), the most popular medications used to treat pain, fever and inflammation. Although their anti-inflammatory effects are well known, their long-term use is associated with gastrointestinal (GI) complications such as ulceration. In 1991, it was discovered that COX exists in two distinct isozymes, COX-1 and COX-2, of which COX-2 is primarily expressed at sites of inflammation and produces pro-inflammatory eicosanoids. For this reason, COX-2 selective inhibitors (COXIBs) have been developed recently as anti-inflammatory agents to minimize the risk of GI toxicity. Recently, some COX-2 selective inhibitors have shown adverse cardiovascular side effects, resulting in the withdrawal of rofecoxib and valdecoxib from the market. Selective inhibition of COX-2 without reducing COX-1-mediated thromboxane production could alter the balance between prostacyclin and thromboxane and promote a prothrombotic state, thereby explaining the observed COX- 2 cardiovascular risk. In this review, we describe mechanisms for the production of pro-inflammatory eicosanoid mediators contributing to inflammation and summarize promising options for the prevention of inflammatory mediator formation and the therapeutic inhibition of pain and inflammation.
Keywords: Arachidonic Acid Metabolism, Lipoxin, Eosinophils, Leukotriene B4 Receptors, ysteinyl-leukotrienes receptors, Inflammation, Fever, Lung Diseases
Current Topics in Medicinal Chemistry
Title: Eicosanoids in Inflammation: Biosynthesis, Pharmacology, and Therapeutic Frontiers
Volume: 7 Issue: 3
Author(s): Subhash P. Khanapure, David S. Garvey, David R. Janero and L. Gordon Letts
Affiliation:
Keywords: Arachidonic Acid Metabolism, Lipoxin, Eosinophils, Leukotriene B4 Receptors, ysteinyl-leukotrienes receptors, Inflammation, Fever, Lung Diseases
Abstract: In mammalian cells, eicosanoid biosynthesis is usually initiated by the activation of phospholipase A2 and the release of arachidonic acid (AA) from membrane phospholipids. The AA is subsequently transformed by cyclooxygenase (COX) and lipoxygenase (LO) pathways to prostaglandins, thromboxane and leukotrienes collectively termed eicosanoids. Eicosanoid production is considerably increased during inflammation. Both COX and LO pathways are of particular clinical relevance. The COX pathway is the major target for non-steroidal anti-inflammatory drugs (NSAIDs), the most popular medications used to treat pain, fever and inflammation. Although their anti-inflammatory effects are well known, their long-term use is associated with gastrointestinal (GI) complications such as ulceration. In 1991, it was discovered that COX exists in two distinct isozymes, COX-1 and COX-2, of which COX-2 is primarily expressed at sites of inflammation and produces pro-inflammatory eicosanoids. For this reason, COX-2 selective inhibitors (COXIBs) have been developed recently as anti-inflammatory agents to minimize the risk of GI toxicity. Recently, some COX-2 selective inhibitors have shown adverse cardiovascular side effects, resulting in the withdrawal of rofecoxib and valdecoxib from the market. Selective inhibition of COX-2 without reducing COX-1-mediated thromboxane production could alter the balance between prostacyclin and thromboxane and promote a prothrombotic state, thereby explaining the observed COX- 2 cardiovascular risk. In this review, we describe mechanisms for the production of pro-inflammatory eicosanoid mediators contributing to inflammation and summarize promising options for the prevention of inflammatory mediator formation and the therapeutic inhibition of pain and inflammation.
Export Options
About this article
Cite this article as:
Khanapure P. Subhash, Garvey S. David, Janero R. David and Gordon Letts L., Eicosanoids in Inflammation: Biosynthesis, Pharmacology, and Therapeutic Frontiers, Current Topics in Medicinal Chemistry 2007; 7 (3) . https://dx.doi.org/10.2174/156802607779941314
DOI https://dx.doi.org/10.2174/156802607779941314 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Innovative Therapeutic Strategies for Restoring Lymphocyte Functions in Septic Patients
Inflammation & Allergy - Drug Targets (Discontinued) Meet Our Editorial Board Member
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Antiretroviral Drugs to Prevent Mother-to-Child Transmission of HIV During Breastfeeding
Current HIV Research Associations of Body Mass Index and Obesity-Related Genetic Variants with Serum Metabolites
Current Metabolomics Immuno-Isolation in Oncology - A Mini-Review
Current Pharmaceutical Biotechnology Adipoparacrinology of Atherosclerosis: Evidence Updated
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Therapeutic Targets in Respiratory Viral Infections
Current Medicinal Chemistry Cancer Cachexia: One Step Ahead
Reviews on Recent Clinical Trials Beta-cell Specific Autoantibodies: Are they Just an Indicator of Type 1 Diabetes?
Current Diabetes Reviews An Atypical Case of Fulminant Interstitial Pneumonitis Induced by Carbamazepine
Current Drug Safety Structure of Multidrug-Resistance Proteins of the ATP-Binding Cassette (ABC) Superfamily
Current Medicinal Chemistry - Anti-Cancer Agents Vaccination Against Leishmania Infections
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Development of Dry Powder Inhalers
Recent Patents on Drug Delivery & Formulation Current and Future Prospective of a Versatile Moiety: Imidazole
Current Drug Targets Synthesis and Evaluation of Thiazolidinedione-Coumarin Adducts as Antidiabetic, Anti-Inflammatory and Antioxidant Agents
Letters in Organic Chemistry Medical Systemic Therapies for Hepatocellular Carcinoma: Clinical Perspectives and Safety Profile
Current Drug Safety Lactoferrin as a Natural Immune Modulator
Current Pharmaceutical Design Biological and Pharmacological Activities of Iridoids: Recent Developments
Mini-Reviews in Medicinal Chemistry Meet Our Editorial Board Member
Recent Patents on Inflammation & Allergy Drug Discovery Non-Selective Cation Channel Blockers: Potential Use in Nervous System Basic Research and Therapeutics
Mini-Reviews in Medicinal Chemistry