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 over more efficiently [29]. Interestingly the concentration of one regioisomer, 7,8-EpDPE that is not a preferred substrate for the sEH is about 30 times higher in the brain and the spinal cord of rats [29]. This suggests that the regioselectivity of both the P450s which make the epoxides and the sEH contribute to the relative concentration of the EFA isomers. Although in many cases the reported outcomes of sEH inhibition is attributed to EETs it is highly likely that other EFAs and their diols are involved. This aspect will be addressed in the following sections. The dihydroxyeicosatrienoic acids (DHETs), diols formed by sEH action on EETs and other EFAs are far more polar and easily conjugated. They seem to lack biological activity in most cases or have lower or different activities from the epoxides though it is difficult to draw a general conclusion for example diols of linoleate epoxides are pro-inflammatory [30, 31]. Besides the sEH mediated degradation the free
