Intestinal Permeability Enhancement: Efficacy, Acute Local Toxicity, and Reversibility
Intestinal Permeability Enhancement: Efficacy, Acute Local Toxicity, and Reversibility
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DOI：
10.1023/a:1018984731584
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发表时间：
1994-08
影响因子：
3.7
通讯作者：
E. Scott Swenson;W. Milisen;W. Curatolo
中科院分区：
文献类型：
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作者：
E. Scott Swenson;W. Milisen;W. Curatolo
在存在多种潜在肠道通透性增强剂的情况下，在大鼠肠道灌注模型中评估了极性药物酚红的吸收。测定吸收速率常数KA和血浆酚红浓度。还检测了灌注液中乳酸脱氢酶（LDH）和磷酸脂的存在，作为肠壁损伤的生化标志物。还对表面活性剂灌注的肠道进行了组织学评估。研究的潜在渗透增强剂是表面活性剂十二烷基硫酸钠 (SDS)、牛磺胆酸钠 (TC)、牛磺脱氧胆酸钠 (TDC)、聚山梨醇酯 80 (PS-80) 和平均极性基团大小为 10.5 POE 单位的壬基苯氧基聚氧乙烯 (NP-POE)。其中，SDS 和 NP-POE-10.5 是最有效的通透性增强剂。胆汁盐 TDC 是比极性更强的 TC 更有效的增强剂。极性非离子表面活性剂PS-80是一种无效的增强剂。酚红KA和血浆水平通常与肠道损伤的生化和组织学指标相关。这些观察结果表明，通透性增强和局部损伤与表面活性剂与肠壁相互作用的后遗症密切相关，并表明局部壁损伤可能参与通透性增强的机制。对表面活性剂 TDC 和 NP-POE-10.5 的渗透性增强和急性局部损伤的可逆性进行了评估。酚红渗透性的增强在增强剂处理停止后1-2小时内被逆转。从灌注液中除去增强剂后 1-2 小时内，局部损伤的生化标记物也降至对照值。灌注肠道的组织学评估显示，形态损伤在 3 小时内逆转。这些结果表明表面活性剂引起的急性肠壁损伤可以快速修复。
The absorption of the polar drug phenol red was assessed in a rat intestinal perfusion model, in the presence of a variety of potential intestinal permeability enhancers. Both the absorption rate constant KAand the plasma phenol red concentration were measured. Perfusates were also assayed for the presence of lactate dehydrogenase (LDH) and lipid phosphate, as biochemical markers of intestinal wall damage. Histological evaluation of surfactant-perfused intestines was also carried out. The potential permeability enhancers studied were the surfactants sodium dodecyl sulfate (SDS), sodium taurocholate (TC), sodium taurodeoxycholate (TDC), polysorbate-80 (PS-80), and nonylphenoxypolyoxyethylene (NP-POE) with an average polar group size of 10.5 POE units. Among these, SDS and NP-POE-10.5 were the most potent permeability enhancers. The bile salt TDC was a more effective enhancer than the more polar TC. The polar non-ionic surfactant PS-80 was an ineffective enhancer. Phenol red KAand plasma level were generally correlated with biochemical and histological measures of intestinal damage. These observations indicate that permeability enhancement and local damage are closely related sequelae of the interaction of surfactants with the intestinal wall, and suggest that local wall damage may be involved in the mechanism of permeability enhancement. The reversibility of permeability enhancement and acute local damage was assessed for the surfactants TDC and NP-POE-10.5. Enhancement of phenol red permeability was reversed within 1-2 hr of the cessation of enhancer treatment. Biochemical markers of local damage also fell to control values within 1-2 hr of removal of enhancer from the perfusate. Histological evaluation of perfused intestines revealed that morphological damage was reversed within 3 hr. These results demonstrate that surfactant-induced acute intestinal wall damage is rapidly repaired.