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J.Health Sci., 56(6), 690-698, 2010
-Regular Article-
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
Atsushi Urano,a, b Kotaro Nishiyama,a
Koichi Kato,a Toru Masaka,b
Mariko Tachikawa,a and Kenzo Yamanaka*, a
aEnvironmental Toxicology and Carcinogenesis Research Unit, Nihon University School of Pharmacy, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan and
bDepartment of Pharmacy, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura, Chiba 285-8741, Japan
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.
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