Physiological and pathophysiological roles of hepoxilins and their analogs

Abstract

The metabolism of arachidonic acid (AA) occurs via different pathways leading to the production of a great number of metabolites with a wide range of biological effects. Hepoxilins (HXs) are physiologically active AA metabolites produced through the lipoxygenase pathway. Since their discovery, several researchers have investigated their biological effects. They were proven to have pro-inflammatory, anti-apoptotic, and skin-protective effects. HXs also contribute to the processes of neutrophil activation and migration and inflammatory hyperalgesia. The major limitation to their effects is that they are highly labile and are metabolized into less active compounds which led to the synthesis of stable HXs analogs called proprietary bioactive therapeutics (PBTs). Although PBTs were synthesized to further study the effect of HXs, they showed different effects than natural HXs under some conditions. PBTs were proven to have anti-inflammatory and anti-cancer effects and were found to be potent antagonists of the thromboxane receptor. In this review article, we aimed to provide an overview of some physiological and pathophysiological effects of hepoxilins and their analogs on the skin, platelet, blood vessel, neutrophil, and cell survival.

Graphical Abstract

Keywords:

• Hepoxilins
• PBT
• skin
• platelets
• neutrophil
• inflammation
• apoptosis
• nervous system

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by a grant from the Canadian Institutes of Health Research [CIHR PS 168846] to A.O.S.E-K. S.H. is the recipient of the Egyptian Government Scholarship.