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Pharmaceutics 2017, 9(1), 9; doi:10.3390/pharmaceutics9010009

Clinical Implications of 20-Hydroxyeicosatetraenoic Acid in the Kidney, Liver, Lung and Brain: An Emerging Therapeutic Target

1
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton T6G 2E1, AB, Canada
2
Department of Basic Medical Sciences, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
*
Author to whom correspondence should be addressed.
Received: 12 January 2017 / Accepted: 15 February 2017 / Published: 20 February 2017
(This article belongs to the Special Issue Pharmacokinetics and Drug Metabolism in Canada: The Current Landscape)
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Abstract

Cytochrome P450-mediated metabolism of arachidonic acid (AA) is an important pathway for the formation of eicosanoids. The ω-hydroxylation of AA generates significant levels of 20-hydroxyeicosatetraenoic acid (20-HETE) in various tissues. In the current review, we discussed the role of 20-HETE in the kidney, liver, lung, and brain during physiological and pathophysiological states. Moreover, we discussed the role of 20-HETE in tumor formation, metabolic syndrome and diabetes. In the kidney, 20-HETE is involved in modulation of preglomerular vascular tone and tubular ion transport. Furthermore, 20-HETE is involved in renal ischemia/reperfusion (I/R) injury and polycystic kidney diseases. The role of 20-HETE in the liver is not clearly understood although it represents 50%–75% of liver CYP-dependent AA metabolism, and it is associated with liver cirrhotic ascites. In the respiratory system, 20-HETE plays a role in pulmonary cell survival, pulmonary vascular tone and tone of the airways. As for the brain, 20-HETE is involved in cerebral I/R injury. Moreover, 20-HETE has angiogenic and mitogenic properties and thus helps in tumor promotion. Several inhibitors and inducers of the synthesis of 20-HETE as well as 20-HETE analogues and antagonists are recently available and could be promising therapeutic options for the treatment of many disease states in the future. View Full-Text
Keywords: 20-hydroxyeicosatetraenoic acid (20-HETE); Cytochrome P450s (CYPs); arachidonic acid (AA); kidney; ischemia/reperfusion (I/R) injury; liver; lung; brain 20-hydroxyeicosatetraenoic acid (20-HETE); Cytochrome P450s (CYPs); arachidonic acid (AA); kidney; ischemia/reperfusion (I/R) injury; liver; lung; brain
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Elshenawy, O.H.; Shoieb, S.M.; Mohamed, A.; El-Kadi, A.O. Clinical Implications of 20-Hydroxyeicosatetraenoic Acid in the Kidney, Liver, Lung and Brain: An Emerging Therapeutic Target. Pharmaceutics 2017, 9, 9.

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