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Review
. 2017 Feb 20;9(1):9.
doi: 10.3390/pharmaceutics9010009.

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

Osama H Elshenawy  1 , Sherif M Shoieb  2 , Anwar Mohamed  3   4 , Ayman O S El-Kadi  5
Affiliations
Review

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

Osama H Elshenawy et al. Pharmaceutics. .

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.

Keywords: 20-hydroxyeicosatetraenoic acid (20-HETE); Cytochrome P450s (CYPs); arachidonic acid (AA); brain; ischemia/reperfusion (I/R) injury; kidney; liver; lung.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Different 20-hydroxyeicosatetraenoic acid (20-HETE) modulators commonly used to study the role of 20-HETE in vivo and in vitro.
Figure 2
Figure 2
Role of 20-HETE in the kidney, liver, lung and brain during normal physiological and pathophysiological conditions.
Figure 3
Figure 3
Enzymes responsible for 20-HETE formation and metabolism in different species.
Figure 4
Figure 4
Role of 20-HETE in elevation of renal vascular resistance.
Figure 5
Figure 5
Role of 20-HETE in regulation of tubular ion transport.
Figure 6
Figure 6
20-HETE role in carcinogenicity.
See this image and copyright information in PMC

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