COX-2, aspirin and metabolism of arachidonic, eicosapentaenoic and docosahexaenoic acids and their physiological and clinical significance.
Polyunsaturated fatty acids (PUFAs) are vital for normal growth and development and physiological function of various tissues in humans. PUFAs have immunomodulatory actions in addition to their ability to modulate inflammation, vascular reactivity, neurotransmission and stem cell biology. PUFAs and their metabolites possess both pro- and anti-inflammatory properties that underlie their actions and involvement in several diseases. Aspirin, a non-steroidal anti-inflammatory drug (NSAID), possesses both cyclo-oxygenase (COX) and lipoxygenase (LOX) inhibitory action and enhances the production of anti-inflammatory lipoxin A4 {(called as epi-lipoxin A4, aspirin-triggered lipoxins (ATLs))}. In addition, at low doses aspirin may not interfere with the production of prostacyclin (PGI2). Both lipoxin A4 and PGI2 have vasodilator, platelet anti-aggregator and anti-inflammatory actions that may underlie the beneficial actions of aspirin. Paradoxically, other NSAIDs may not have the same actions as that of aspirin on PUFA metabolism. Similar anti-inflammatory compounds are formed from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by the action of aspirin termed as resolvins (from EPA and DHA) and protectins and maresins from DHA. PUFAs: arachidonic acid (AA), EPA and DHA and their various products modulate not only inflammation and immune response but also possess actions on various genes, nuclear factors, cyclic AMP and GMP, G-protein coupled receptors (GPRs), hypothalamic neurotransmitters, hormones, cytokines and enzymes, and interact with nitric oxide, carbon monoxide, and hydrogen sulfide to regulate their formation and action and to form new compounds that have several biological actions. These pleiotropic actions of PUFAs and their metabolites may explain their ability to play a role in several physiological actions and diseases. The big challenge is to harness these actions to prevent and manage clinical conditions.
Insitute of Nuclear Medicine and Allied Sciences, DRDO, Delhi, India; BioScience Research Centre, Gayatri Vidya Parishad College of Engineering Campus, Visakhapatnam 530 048, India.
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R
Poorani
Insitute of Nuclear Medicine and Allied Sciences, DRDO, Delhi, India.
Anant N
AN
Bhatt
Insitute of Nuclear Medicine and Allied Sciences, DRDO, Delhi, India.
B S
BS
Dwarakanath
BioScience Research Centre, Gayatri Vidya Parishad College of Engineering Campus, Visakhapatnam 530 048, India; UND Life Sciences, 2020 S 360th St, # K-202, Federal Way, WA 98003, USA. Electronic address: undurti@hotmail.com.
Undurti N
UN
Das
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism* / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000378:metabolism* / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid; D051546:Cyclooxygenase 2; D001241:Aspirin
Aspirin; Lipoxins; Nitric oxide; Polyunsaturated fatty acids; Prostaglandins; Resolvins