Substantial reaction between histamine and malondialdehyde: a new observation of carbonyl stress.

OBJECTIVES To explore the mechanism of carbonyl stress-related toxification on neurotransmitter histamine and the potential de-carbonylation function of histamine. METHODS The reaction mixture of malondialdehyde (MDA) and histamine (HA) at pH7.4, 37 degrees C was assayed by high performance liquid chromatography (HPLC), spectrophotometry and spectrofluorometry. The reaction products were assayed by LC/MS. RESULTS In physiological condition, the reaction of MDA and HA yielded two products: a nonfluorescent enaminal derivatives and a fluorescent 1,4-dihydropyridine adducts. The fluorescence maxima of the fluorescent products (Ex. 393 nm/Em. 464 nm) were similar to those of lipofuscin pigment. The fluorescence intensity of reaction mixture was in direct proportion to the MDA concentration. CONCLUSIONS HA can react with MDA to form stable products, a non-fluorescent enamine (product 1) and a fluorescent 1,4-dihydropyridine (product 2) which are ceroid/lipofuscin-related adducts. The reaction of HA with MDA may reveal toxic effect of unsaturated carbonyls in the brain and may reflect a novel de-carbonylation function of histamine under various pathological conditions.