Department of Morphological Sciences, State University of Maringá, Colombo Avenue, 5790, CEP: 87020-900, Maringá, Paraná, Brazil.
Campus Uruguaiana, Federal University of Pampa, BR 472 - Km 592, CEP: 97508-000, Uruguaiana, Rio Grande do Sul, Brazil.
Toxicology. 2018 Mar 1;396-397:13-22. doi: 10.1016/j.tox.2018.02.002. Epub 2018 Feb 7.
The gastrointestinal tract is extremely sensitive to ischemia and reperfusion (I/R). Studies have reported that resveratrol (RSV) is able to combat damage caused by intestinal I/R. Because of its effectiveness in increasing the permanence and bioavailability of resveratrol in the intestinal epithelium, we investigated whether the effect of resveratrol-loaded in poly(anhydride) nanoparticles reduce oxidative stress and promote myenteric neuroprotection in the ileum of rats subjected to I/R. Physicochemical evaluations were performed on nanoparticles. The animals were divided into nine groups (n = 6/group) and treated every 48 h. Treatments with resveratrol (7 mg/kg of body weight) were applied 5 days before surgery and continued for 7 days after surgery (reperfusion period). The superior mesenteric artery was occluded to cause I/R injury. Oxidative stress, myeloperoxidase, nitrite, aspartate aminotransferase, alanine aminotransferase, immunolabeling of myenteric neurons and glial cells, and gastrointestinal transit was evaluated. Both nanoparticle formulations presented negative charge with homogeneous distribution, and the payload, showed an encapsulation efficiency of 60%. Resveratrol administered in free form prevented alterations that were caused by I/R. The results of the groups treated with RSV-loaded nanoparticles presented similar results to the group treated with free resveratrol. Treatment with empty nanoparticles showed that poly(anhydride) is not an ideal nanocarrier for application in in vivo models of intestinal I/R injury, because of hepatotoxicity that may be caused by epithelial barrier dysfunction that triggers the translocation of nanoparticles.
胃肠道对缺血再灌注(I/R)极为敏感。研究报道白藜芦醇(RSV)能够对抗肠道 I/R 引起的损伤。由于其能够提高肠上皮中白藜芦醇的稳定性和生物利用度,我们研究了负载在聚(酸酐)纳米粒子中的白藜芦醇是否能减轻氧化应激并促进 I/R 大鼠回肠的肌间神经保护作用。对纳米粒子进行了理化评价。将动物分为 9 组(n=6/组),并每 48 h 进行一次治疗。在手术前 5 天和手术后 7 天(再灌注期),以 7mg/kg 体重的剂量给予白藜芦醇治疗。结扎肠系膜上动脉造成 I/R 损伤。评估氧化应激、髓过氧化物酶、亚硝酸盐、天门冬氨酸转氨酶、丙氨酸转氨酶、肌间神经元和神经胶质细胞的免疫标记以及胃肠道转运。两种纳米粒子制剂均带负电荷且分布均匀,载药量显示出 60%的包封效率。以游离形式给予白藜芦醇可预防 I/R 引起的改变。负载 RSV 的纳米粒子治疗组的结果与游离白藜芦醇治疗组相似。用空纳米粒子治疗组表明,聚(酸酐)不是应用于肠道 I/R 损伤的体内模型的理想纳米载体,因为上皮屏障功能障碍可能导致纳米粒子的易位,从而引发肝毒性。