epoxide hydrolase in mouse liver; since it is widely distributed in various tissues of various mammalian species, including humans, soluble epoxide hydrolase may be the principal enzyme responsible for metabolizing these and perhaps other hepoxilin compounds. It seems possible, however, that other similarly acting epoxide hydrolases such as microsomal epoxide hydrolase or epoxide hydrolase 2 may prove to hepoxilin hydrolase activity. While the trihydroxy products of hepoxilin synthesis are generally considered to be inactive and the sEH pathway therefore considered as functioning to limiting the actions of the hepoxilins, some studies found that TrXA3, TrXB3, and TrXC3 were more powerful than HxA3 in relaxing pre-contracted mouse arteries and that TrXC3 was a relatively potent relaxer of rabbit pre-contracted aorta. HxA3 was converted through a Michael addition catalyzed by glutathione transferase to its glutathione conjugate, HxA3-C, i.e., 11-glutathionyl-HxA3, in a cell-free system or in homogenates of rat brain hippocampus tissue; HxA3-C proved to be a potent stimulator of membrane hyperpolarization in rat hippocampal CA1 neurons. This formation of hepoxilin A3-C appears analogous to the formation of leukotriene C4 by the conjugation of glutathione to leukotriene A4. Glutathione conjugates of 14,15-HxA3 and 14,15-HxB3 have also been detected the human Hodgkin disease Reed–Sternberg cell line, L1236. HxB3 and TrX3 are found esterified into the sn-2 position of phospholipid in human psoriasis lesions and samples of human psoriatic skin acylate HxBw and TrX2 into these phospholipids in vitro. Physiological effects Virtually all of the biological studies on hepoxilins have been conducted in animals or in vitro on animal and human tissues, However, these studies give species-specific different results which complicate their relevancy to humans. The useful translation of these studies to human physiology, pathology, and clinical medicine and therapies requires much further study. Inflammation HxA3 and HxB3 possess pro-inflammatory actions in, for example, stimulating human neutrophil chemotaxis and increasing the permeability of skin capillaries. Studies in humans have found that the amount of HxB3 is >16-fold higher in psoriatic lesions than normal epidermis. It is present in psoriatic scales at ~10 micromolar, a concentration which is able to exert biologic effects; HxB3 was not detected in these tissues although its present was strongly indicated by the presence of its metabolite, TrXB3, at relatively high levels in psoriatic scales but not normal epidermal tissue. These results suggest that the pro-inflammatory effects of HxA3 and HxB3 may contribute to the inflammatory response that accompanies psoriasis and