Catalyzes the NAD-dependent dehydrogenation (oxidation) of a broad array of hydroxylated polyunsaturated fatty acids (mainly eicosanoids and docosanoids, including prostaglandins, lipoxins and resolvins), yielding their corresponding keto (oxo) metabolites (PubMed:9099857) (By similarity). Decreases the levels of the pro-proliferative prostaglandins such as prostaglandin E2 (whose activity is increased in cancer because of an increase in the expression of cyclooxygenase 2) and generates oxo-fatty acid products that can profoundly influence cell function by abrogating pro-inflammatory cytokine expression. Converts resolvins E1, D1 and D2 to their oxo products, which represents a mode of resolvin inactivation. Resolvin E1 plays important roles during the resolution phase of acute inflammation, while resolvins D1 and D2 have a unique role in obesity-induced adipose inflammation (By similarity). NAD(+) + prostaglandin E2 = 15-oxoprostaglandin E2 + H(+) + NADH (5Z,8Z,11Z,13E,15S)-hydroxyeicosatetraenoate + NAD(+) = 15-oxo-(5Z,8Z,11Z,13E)-eicosatetraenoate + H(+) + NADH (11R)-hydroxy-(5Z,8Z,12E,14Z)-eicosatetraenoate + NAD(+) = 11-oxo-(5Z,8Z,12E,14Z)-eicosatetraenoate + H(+) + NADH lipoxin A4 + NAD(+) = 15-oxo-(5S,6R)-dihydroxy-(7E,9E,11Z,13E)-eicosatetraenoate + H(+) + NADH 15-oxo-(5S,6R)-dihydroxy-(7E,9E,11Z)-eicosatrienoate + H(+) + NADH = (5S,6R,15S)-trihydroxy-(7E,9E,11Z)-eicosatrienoate + NAD(+) NAD(+) + prostaglandin A1 = 15-oxo-prostaglandin A1 + H(+) + NADH NAD(+) + prostaglandin E1 = 15-oxoprostaglandin E1 + H(+) + NADH 14-hydroxy-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoate + NAD(+) = 14-oxo-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoate + H(+) + NADH NAD(+) + resolvin E1 = 18-oxo-resolvin E1 + H(+) + NADH NAD(+) + resolvin D1 = 8-oxoresolvin D1 + H(+) + NADH NAD(+) + resolvin D1 = 17-oxoresolvin D1 + H(+) + NADH NAD(+) + resolvin D2 = 7-oxoresolvin D2 + H(+) + NADH NAD(+) + resolvin D2 = 16-oxoresolvin D2 + H(+) + NADH Homodimer. Belongs to the short-chain dehydrogenases/reductases (SDR) family.