Amino acids protect epithelial cells from local toxicity by absorption enhancer, sodium laurate.
Amino acids protect epithelial cells from local toxicity by absorption enhancer, sodium laurate.
复制标题
氨基酸通过吸收促进剂月桂酸钠保护上皮细胞免受局部毒性。
DOI：
10.1002/jps.1097
复制
发表时间：
2001
影响因子：
3.8
通讯作者：
T. Kimura
中科院分区：
文献类型：
--
作者：
T. Yata;Y. Endo;M. Sone;K. Ogawara;K. Higaki;T. Kimura
为了开发安全的吸收增强制剂来减轻吸收促进剂月桂酸钠 (C12) 引起的局部毒性，在大鼠中检查了氨基酸对 C12 局部毒性的影响。在一项原位结肠环研究中，10 mM C12 显着增强了不可吸收标记药物酚红的吸收，并且添加 10 mM L-谷氨酰胺 (L-Gln)、L-精氨酸或 L-蛋氨酸并没有改变 C12 的促进作用。然而，C12显着增加了作为局部毒性标志物的磷脂、总蛋白和乳酸脱氢酶从结肠的洗脱，但这些氨基酸显着减弱了C12引起的局部毒性。使用 Ussing 型室进行的转运研究表明，C12 显着增强了结肠膜对酚红的通透性，并且 L-Gln 并未降低 C12 增强的通透性。 C12 显着降低了跨粘膜电阻，表明 C12 至少可以部分通过扩大细胞旁途径来增强药物吸收。 L-Gln 显着（但并非完全）恢复了 C12 降低的耐药性。 C12 显着降低了电位差，表明 C12 降低了粘膜细胞的活力，但 10 mM L-Gln 显着地将电位差恢复到几乎与对照水平。这些结果表明，通过使用L-Gln等氨基酸作为减轻C12引起的局部毒性的成分，可以开发出具有低局部毒性的吸收促进制剂，其低到足以实际使用。
To develop the safe absorption-enhancing formulation attenuating the local toxicity caused by an absorption enhancer, sodium laurate (C12), the effects of amino acids on the local toxicity by C12 were examined in rats. The absorption of phenol red, an unabsorbable marker drug, was significantly enhanced by 10 mM C12 in an in situ colon loop study and the addition of L-glutamine (L-Gln), L-arginine, or L-methionine at 10 mM did not change the promoting effect of C12. However, C12 significantly increased the elution of phospholipids, total protein, and lactate dehydrogenase, which are markers for local toxicity, from colon, but these amino acids attenuated the local toxicity caused by C12 significantly. Transport study using an Ussing-type chamber showed that the permeability of colonic membrane to phenol red was significantly enhanced by C12 and that L-Gln did not decrease the permeability enhanced by C12. Transmucosal electrical resistance was extensively decreased by C12, indicating that C12 could enhance the drug absorption at least partly by expanding the paracellular route. L-Gln significantly, but not completely, recovered resistance lowered by C12. Electrical potential difference was markedly reduced by C12, suggesting that C12 lowered the viability of mucosal cells, but 10 mM L-Gln significantly recovered potential difference almost to the control level. These results suggested the possibility that absorption-enhancing formulation with low local toxicity, which is low enough to be used practically, could be developed by using an amino acid like L-Gln as an ingredient attenuating the local toxicity caused by C12.
DOI：
10.1152/ajpgi.1997.272.4.g879
发表时间：
1997-04
期刊：
The American journal of physiology
影响因子：
--
作者：
P. Wischmeyer;M. Musch;M. Madonna;R. Thisted;E. Chang
通讯作者：
P. Wischmeyer;M. Musch;M. Madonna;R. Thisted;E. Chang