Identification of novel oxidized levuglandin D 2 in marine red alga and mouse tissue

In animals, the product of cyclooxygenase reacting with arachidonic acid, prostaglandin(PG)H 2, can undergo spontaneous rearrangement and nonenzymatic ring cleavage to form levuglandin(LG)E 2 and LGD 2. These LGs and their isomers are highly reactive γ-ketoaldehydes that form covalent adducts with proteins, DNA, and phosphatidylethanolamine in cells. Here, we isolated a novel oxidized LGD 2 (ox-LGD 2 ) from the red alga Gracilaria edulis and determined its planar structure. Additionally, ox-LGD 2 was identified in some tissues of mice and in the lysate of phorbol-12-myristate-13-acetate (PMA)-treated THP-1 cells incubated with arachidonic acid using LC-MS/MS. These results suggest that ox-LGD 2 is a common oxidized metabolite of LGD 2. In the planar structure of ox-LGD 2, H8 and H12 of LGD 2 were dehydrogenated and the C9 aldehyde was oxidized to a carboxylic acid, which formed a lactone ring with the hydrated ketone at C11. These structural differences imply that ox-LGD 2 is less reactive with amines than LGs. Therefore, ox-LGD 2 might be considered a detoxification metabolite of LGD 2.