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Evaluation of the treatment with resveratrol-loaded nanoparticles in intestinal injury model caused by ischemia and reperfusion

Borges, Stephanie Carvalho, Ferreira, Paulo Emílio Botura, da Silva, Luisa Mota, de Paula Werner, Maria Fernanda, Irache, Juan Manuel, Cavalcanti, Osvaldo Albuquerque, Buttow, Nilza Cristina
Toxicology 2018 v.396-397 pp. 13-22
alanine transaminase, aspartate transaminase, bioavailability, body weight, encapsulation, gastrointestinal transit, hepatotoxicity, ileum, intestinal mucosa, ischemia, mesenteric arteries, models, myeloperoxidase, nanocarriers, nanoparticles, neuroglia, neurons, neuroprotective effect, nitrites, oxidative stress, rats, resveratrol, surgery
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.