Abstract
Organ fibrosis often ends in eventual organ failure and leads to high mortality. Although researchers have identified many effector cells and molecular pathways, there are few effective therapies for fibrosis to date and the underlying mechanism needs to be examined and defined further. Epoxyeicosatrienoic acids (EETs) are endogenous lipid metabolites of arachidonic acid (ARA) synthesized by cytochrome P450 (CYP) epoxygenases. EETs are rapidly metabolized primarily via the soluble epoxide hydrolase (sEH) pathway. The sEH pathway produces dihydroxyeicosatrienoic acids (DHETs), which have lower activity. Stabilized or increased EETs levels exert several protective effects, including pro-angiogenesis, anti-inflammation, anti-apoptosis, and anti-senescence. Currently, intensive investigations are being carried out on their anti-fibrotic effects in the kidney, heart, lung, and liver. The present review provides an update on how the stabilized or increased production of EETs is a reasonable theoretical basis for fibrosis treatment.
Highlights
cytochrome P450 (CYP) epoxygenase genes are expressed in most tissues, there is significant inter-tissue variability, such that Epoxyeicosatrienoic acids (EETs) formation is different in the various organs, and this can significantly influence the physiological response of a given tissue [3]
diabetic nephropathy (DN) by reducing renal interstitial fibrosis [47]. These results suggest that EETs may have a reno-protective effect in chronic kidney disease, evidenced by studies using the potent sEH inhibitor (sEHI) and other enzymes to amplify endogenous EETs
EETfibrosis levelsvia appear to pathways be increased in cirrhotic portal circulation
Summary
The increased EET levels shift ARA metabolism to other pro-inflammatory pathways (e.g., ω-hydrolase-LOX pathways), and this counteracts the increase in EETs [11]. Other approaches, such as CYP2J2 overexpression, EET analog treatment, and exogenous EET treatment, are widely used [9,12,13,14]. Dependent effects of EETs. At any rate, the sEH inhibitor (sEHI) has advanced further toward clinical use than other metabolites. EETs. At any rate, the sEH inhibitor (sEHI) has advanced further toward clinical use than other metabolites. Increased production of EETs leads to possible therapies for fibrosis. Zation or increased production of EETs leads to possible therapies for fibrosis
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