Low-molecular Weight Amines Have Marked Potential to Promote Colitis in a Mouse Experimental Model: A Possible Proposal of in vivo Formation of Their Chloramines

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We have reported that methylamine dichloramine (CH₃NCl₂) causes colitis in mice and that in addition to its oxidative potentials, its cell membrane permeability is important for the onset of ulcerative colitis (UC). The aim of the present study was to determine if CH₃NH₂, a typical low-molecular weight biological amine, aggravates experimental UC in mice through in vivo formation of its chloramines. The biological oxidation potentials of low-molecular chloramines (50-200 μM) were evaluated by hemolysis and methemoglobin formation in sheep erythrocytes (1×10⁸ cells/ml). ICR-strain mice were administered drinking water containing 1.5% dextran sulfate sodium (DSS), a potent UC inducer in mice, for 6 days. The mice were intraperitoneally administered CH₃NH₂ (5-40mg/kg per day) for 5 days. The colonic lesions were characterized by visible parameters and microscopic analysis of histological alterations and the number of infiltrating and myeloperoxidase positive neutrophils, respectively. Methylamine chloramines showed considerably higher potentials for both hemolysis and methemoglobin formation than the other chloramines tested. The administration of CH₃NH₂ increased the excretion of CH₃NH₂ itself into feces in a dose-dependent manner and markedly aggravated experimental UC accompanying the increased neutrophil infiltration. These results strongly support the possibility that CH₃NH₂ causes serious aggravation in UC via the formation of its chloramines and suggest the participation of low-molecular weight biological amines in deteriorating colitis.