Anti- and pro-oxidant effects of quercetin stabilized by microencapsulation on interstitial cells of Cajal, nitrergic neurons and M2-like macrophages in the jejunum of diabetic rats

• Published in: Neurotoxicology (Park Forest South) 2020-03, Vol.77, p.193-204
• Main Authors: Vieira-Frez, Flávia Cristina, Sehaber-Sierakowski, Camila Caviquioli, Perles, Juliana Vanessa Colombo Martins, Bossolani, Gleison Daion Piovezana, Verri, Waldiceu Aparecido, Nascimento, Rafael Campos do, Guarnier, Flávia Alesandra, Bordini, Heloíza Paranzini, Blegniski, Fernanda Pachoal, Martins, Heber Amilcar, de Souza, Sara Raquel Garcia, Lima, Fabiana Galvão da Motta, Lima, Mariana Machado, Silva, Bruna Thais, Iwanaga, Camila Cristina, Zanoni, Jacqueline Nelisis
• Format: Article
• Language: English
• Subjects: Animals; Antioxidant; Antioxidants; Antioxidants - administration & dosage; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 1 - chemically induced; Diabetes Mellitus, Type 1 - metabolism; Drug Compounding; Interstitial cells; Interstitial cells of Cajal; Jejunum; Jejunum - drug effects; Jejunum - metabolism; M2-like macrophages; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Male; Microcapsules; Microencapsulation; Myenteric Plexus - drug effects; Myenteric Plexus - metabolism; Neurons; Neuroprotection; Nitrergic Neurons - drug effects; Nitrergic Neurons - metabolism; Oxidants; Oxidative stress; Oxidative Stress - drug effects; Oxidizing agents; Quercetin; Quercetin - administration & dosage; Quercetin stabilized by microencapsulation; Rats, Wistar; Rodents; Streptozocin - administration & dosage; Telocytes - drug effects; Telocytes - metabolism; Toxicity
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2020.01.011

[Display omitted] •The diabetes-induced oxidative stress affects interstitial cells of Cajal (ICC), nitrergic neurons and M2-like macrophages.•Quercetin-loaded microcapsules (100 mg kg−1) aggravated the diabetic condition with toxic activities to the healthy animals.•Quercetin-loaded microcapsules (10 mg kg−1) displayed desirable and protective effects on diabetic and healthy rats. Given the well-known antioxidant and neuroprotective properties of quercetin, the aim of this work was to evaluate the effects of quercetin stabilized by microencapsulation at two doses (10 mg kg−1 and 100 mg kg−1) on the oxidative/antioxidant status, number and morphological features of ICC, nitrergic neurons and M2-like macrophages in jejunum of diabetic rats. The rats were randomly distributed into six groups: normoglycemic control (N), diabetic control (D) and either normoglycemic or diabetic groups treated with quercetin-loaded microcapsules at a dose of 10 mg kg−1 (NQ10 and DQ10, respectively) or 100 mg kg−1 (NQ100 and DQ100, respectively). After 60 days, the jejunum was collected. Whole mounts were immunostained for Ano1, nNOS and CD206, and oxidative stress levels and total antioxidant capacity of the jejunum were measured. Diabetes led to a loss of ICC and nitrergic neurons, but increased numbers of M2-like macrophages and elevated levels of oxidative stress were seen in diabetic animals. High-dose administration of quercetin (100 mg kg−1) further aggravated the diabetic condition (DQ100) but this treatment resulted in harmful effects on healthy rats (NQ100), pointing to a pro-oxidant activity. However, low-dose administration of quercetin (10 mg kg−1) gave rise to antioxidant and protective effects on ICC, nNOS, macrophages and oxidative/antioxidant status in DQ100, but NQ100 displayed infrequent negative outcomes in normoglycemic animals. Microencapsulation of the quercetin may become promising alternatives to reduce diabetes-induced oxidative stress but antioxidant therapies should be careful used under healthy status to avoid toxic effects.