In macrophages, cytochrome P450s (CYPs) are likely to 21-hydroxylate 14(R)-hydroxy-docosahexaenoic acid (14(R)-HDHA) to 14(R),21(R)-dihydroxy-docosahexaenoic acid (14(R),21(R)-diHDHA) and 14(R),21(S)-diHDHA (Lu et al. 2010). In human skin, CYP1A1, 2B6/7, 2E1, 3A4/7, and 3A5 proteins have been identified and shown to possess catalytic activities (Swanson 2004). CYP2E1 is able to generate 19-hydroxyleicosatetraenoic acid, an ω-1 hydroxylation intermediate of arachidonic acid (Laethem et al. 1993) therefore, it might also ω-1 hydroxylate 14(R)-HDHA in human skin.
Administration of 14,21-diHDHA stereoisomers to splinted excisional wounded mice demonstrated their involvement in wound pro-healing processes (Lu et al. 2010).