Epoxygenated fatty acid metabolites are subject to several routes of metabolism with rapid degradation by the soluble epoxide hydrolase enzyme predominant [18]. The soluble epoxide hydrolase (sEH) is an enzyme downstream of cytochrome P450 expoygenases in the AA cascade [18]. It is expressed in the brain and CNS [23, 24] although higher expression levels occur in liver and kidneys of studied species including humans [25]. The sEH is the principal epoxide hydrolase responsible for the enzymatic degradation of EETs to corresponding diol products [26, 27]. Endogenous free EETs have a short half-life given their degradation via sEH [13]. In support of the role of sEH in the metabolism of EFAs, the genetic knock out of the sEH expression in the mouse leads to approximately 3 times higher plasma levels of summed EETs compared to congenic wild type animals [28]. We recently demonstrated that epoxides of EPA and DHA are both natural substrates of the sEH and are rapidly metabolized by this enzyme [29]. The epoxides of DHA are arguably better substrates for sEH than the EETs since they are turned
