薬理と治療

Abstract

Non︱steroidal anti︱inflammatory drugs（NSAIDs）are among the most commonly prescribed medications worldwide, but cause damage in the small intestine as well as stomach. Probiotic preparations, especially containing live lactic acid bacteria, have been used for treatment of bowel disturbances such as diarrhea and constipation. In the present study, we examined the effect of various probiotic preparations on the development of intestinal lesions induced in rats by loxoprofen, a NSAID frequently used in Asian countries. The single oral administration of loxoprofen（60 mg╱kg）caused severe intestinal lesions, accompanied by the increase in myeloperoxidase（MPO）activity and inducible nitric oxide（iNOS）mRNA expression. The pretreatment with various lactic acid︱producing probiotic preparations such as Lactomin preparation, Bifidobacterium preparation, and Lactobacillus casei preparation for 7 days significantly suppressed the severity of loxoprofen︱induced intestinal lesions. However, the pretreatment with Butyric acid bacteria preparation, failed to prevent these lesions. The increase in MPO activity and iNOS mRNA expression induced by loxoprofen was also significantly suppressed by the pretreatment with probiotic preparations of Lactomin, Bifidobacterium, and Lactobacillus casei, but not Butyric acid bacteria. Likewise, repeated oral administration of loxoprofen（30 mg╱kg）for 3 days similarly caused severe intestinal lesions, accompanied by the increase in MPO activity, and these responses were significantly attenuated by twice︱daily administration of Lactomin preparation. These findings suggest that probiotic preparations of Lactomin, Bifidobacterium, and Lactobacillus casei prevent loxoprofen︱induced intestinal lesions. This action may be mediated by the suppression of neutrophil infiltration and iNOS induction, probably via controlling intestinal flora. Thus, lactic acid︱producing probiotic preparations may be useful for preventing NSAID︱induced small intestinal lesions.