ELUCIDATION OF MECHANISMS BEHIND CYTOPROTECTIVE EFFECTS OF AMINO ACIDS: IMPROVEMENT OF MUCOSAL INJURY CAUSED BY ABSORPTION ENHANCER
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概要
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To develop the absorption enhancing formulation with local toxicity low enough for the practical use, we have investigated the effect of amino acids on the local toxicity and the absorption enhancement caused by sodium laurate (C12), used as an absorption enhancer. As a result, the absorption of phenol red (PR), an unabsorbable marker, was enhanced significantly by applying 10 mM C12 and the addition of amino acids did not change this absorption-enhancing effect of C12 in <I>in situ</I> colon loop study. On the other hand, although C 12 significantly increased the elution of phospholipids, proteins, and lactate dehydrogenase from colon, which are biological markers for local toxicity, amino acids significantly attenuated this mucosal injury caused by C12. In the present study, we tried to elucidate the mechanism involved in the protective effects of amino acids against mucosal injury caused by C12, and HSP70 was suggested to be involved in the cytoprotection by L-glutamine. Furthermore, the attenuation of intracellular Ca<SUP>2+</SUP>level and of histamine release, which are enhanced by C12, were also suggested to be mechanisms behind the cytoprotective action of amino acids.
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