10-Hydroxy-2-decenoic acid-derived aldehydes attenuate anaphylactic hypothermia in vivo

Background: A royal jelly-derived unique fatty acid, 10-hydroxy-2-decenoic acid (10-HDA), attenuates anaphy-lactic hypothermia by inhibiting the bioactivities of platelet-activating factor (PAF) and histamine, which are known mediators of anaphylaxis in vivo. Here, we investigated the effects of 10-HDA and its two metabolites, 2-decenedioic acid (2-DA) and 3-hydroxysebacic acid (3-HSA), on anaphylactic hypothermia targeting PAF and histamine in vivo. Methods: The effects of 10-HDA and its metabolites on the bioactivities of PAF and histamine, and anaphylactic hypothermia were evaluated in a rat hind paw edema model and an anaphylactic mouse model.Results: The metabolites, 2-DA and 3-HSA, barely inhibited histamine-and PAF-induced paw edema in rats. Oral ingestion of 10-HDA (0.002 % and 0.02 %) with food attenuated anaphylactic hypothermia in a dose-dependent manner, whereas intraperitoneal injection of 2-DA or 3-HSA did not inhibit hypothermia. 4-Methylpyrazole, an inhibitor of alcohol dehydrogenase, which converts 10-HDA to its aldehydes, 10-oxo-decenoic acid (10-ODA) and 10-oxo-3-hydroxysebacic acid (10-OHSA), inhibited 10-HDA-induced attenuation of anaphylactic hypothermia. In contrast, cyanamide, an inhibitor of aldehyde dehydrogenase, which converts 10-ODA and 10-OHSA to 2-DA and 3-HSA enhanced the attenuation effect of 10-HDA.Conclusions: The results suggest that 10-HDA-derived aldehydes, 10-ODA and 10-OHSA, may play a key role in the attenuation of anaphylactic hypothermia in vivo.