Abstract
Diamine oxidase (DAO) administration has been proposed to treat certain gastrointestinal dysfunctions induced by histamine, an immunomodulator, signaling, and pro-inflammatory factor. However, H2O2 resulting from the oxidative deamination of histamine by DAO may be toxic. The purpose of this study was to investigate to which extent DAO from white pea (Lathyrus sativus), alone or in combination with catalase, may modulate histamine toxicity in the human intestinal Caco-2 cell line. The results show that histamine at concentrations higher than 1 mM is toxic to the Caco-2 cells, independently of the cell differentiation status, with a LC50 of ≅ 10 mM following a 24-h exposure. Depending on its concentration, DAO increased histamine toxicity to a greater extent in differentiated cells compared to undifferentiated cultures. In the presence of catalase, the DAO-induced increase in histamine toxicity was completely abolished in the undifferentiated cells and only partially decreased in differentiated cells, showing differences in the sensitivity of Caco-2 cells to the products resulting from histamine degradation by DAO (H2O2, NH3, or imidazole aldehyde). It appears that treatment of food histaminosis using a combination of vegetal DAO and catalase would protect against histamine toxicity and prevent H2O2-induced damage that may occur during histamine oxidative deamination.
Highlights
Food histaminosis, associated with pseudo allergic phenomena, may occur upon ingestion of histamine-containing foods, such as red wine, beer, chocolate, sauerkraut, fish, and processed meats
This disorder is more frequent in people with low level of intestinal histaminase [1, 2], a copper-containing diamine oxidase (DAO, EC 1.4.3.22) able to catalyze the oxidative decomposition of histamine and producing H2O2, NH3, and imidazole acetaldehyde
Time-course of histamine consumption upon addition of Diamine oxidase (DAO) isolated from Lathyrus sativus in Fetal bovine serum (FBS)-free Dulbecco’s Modified Eagle minimum essential medium (DMEM) well fitted a first-order decay equation (Y = Ymax × e−kt) allowing the estimation of the rate constants of consumption (k) and t1/2 values representing time for which degradation is half-completed (Fig. 1, circles)
Summary
Food histaminosis, associated with pseudo allergic phenomena, may occur upon ingestion of histamine-containing foods, such as red wine, beer, chocolate, sauerkraut, fish, and processed meats. Histaminosis is an enteric dysfunction that often affects the population in industrialized countries. This disorder is more frequent in people with low level of intestinal histaminase [1, 2], a copper-containing diamine oxidase (DAO, EC 1.4.3.22) able to catalyze the oxidative decomposition of histamine and producing H2O2, NH3, and imidazole acetaldehyde. The sensitivity to histamine is associated to symptoms such as gastro-intestinal discomfort [3, 4], migraine [5], irritation of nasal mucosa, itching, and other forms of allergy [6]. Lowered activity of histamine catabolism has been shown in colonic mucosa of patients with colonic adenomas [8]
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