Diamine Oxidase from White Pea (Lathyrus sativus) Combined with Catalase Protects the Human Intestinal Caco-2 Cell Line from Histamine Damage.

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.

The fungicide thiabendazole causes apoptosis in rat hepatocytes.

Many pharmaceutical drugs cause hepatotoxicity in humans leading to severe liver diseases, representing a serious public health issue. This study investigates the ability of the anthelmintic and antifungal drug thiabendazole to cause cell death by apoptosis and metabolic changes in primary cultures of rat hepatocytes. Thiabendazole (200-500 µM) induced apoptosis in hepatocytes after 1 to 24h, causing loss of mitochondrial membrane potential, cytochrome c release from mitochondria, Fas-associated death domain (FADD) translocation from the cytosol to membranes, and activation of caspases-3, -8 and -9. Thus, thiabendazole activated both the mitochondrial and death receptor pathways of apoptosis. Under these conditions, cell death by necrosis was not detected following exposure to thiabendazole (100-500 µM) for 24-48 h, measured by lactate dehydrogenase release and propidium iodide uptake. Furthermore, thiabendazole increased activities of cytochrome P450 (CYP) isoenzymes CYP1A and CYP2B after 24 and 48 h, determined by 7-ethoxyresorufin-O-deethylase (EROD) and 7-pentoxyresorufin-O-dealkylase (PROD) activities, respectively. An important finding is that thiabendazole can eliminate hepatocytes by apoptosis, which could be a sensitive marker for hepatic damage and cell death. This study improves understanding of the mode of cell death induced by thiabendazole, which is important given that humans and animals are exposed to this compound as a pharmaceutical agent and in an environmental context.