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.

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