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Clinical Implications of 20-Hydroxyeicosatetraenoic Acid in the Kidney, Liver,
Lung and Brain: An Emerging Therapeutic Target
#MMPMID28230738
Elshenawy OH
; Shoieb SM
; Mohamed A
; El-Kadi AO
Pharmaceutics
2017[Feb]; 9
(1
): ? PMID28230738
show ga
Cytochrome P450-mediated metabolism of arachidonic acid (AA) is an important
pathway for the formation of eicosanoids. The ?-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.
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