da Costa Güllich Angélica Aparecida, Coelho Ritiéle Pinto, Pilar Bruna Cocco, Ströher Deise Jaqueline, Galarça Leandro Alex Sander Leal, Vieira Simone Machado, da Costa Escobar Piccoli Jacqueline, Haas Sandra Elisa, Manfredini Vanusa
Postgraduate Program in Biochemistry, Federal University of Pampa, Uruguaiana, Rio Grande do Sul, Brazil.
Metab Brain Dis. 2015 Jun;30(3):695-702. doi: 10.1007/s11011-014-9621-5. Epub 2014 Oct 9.
Clozapine, atypical antipsychotic, can change oxidative stress parameters. It is known that reactive species, in excess, can have a crucial role in the etiology of diseases, as well as, can potentiating adverse effects induce by drugs. The nanocapsules have attracted attention as carriers of several drugs, with consequent reduction of adverse effects. This study aimed to evaluate histopathology and oxidative damage of biomolecules lipids, proteins and DNA in the brain of Wistar rats after treatment with nanocapsules containing clozapine. The study consisted of eight groups of male Wistar rats (n = 6): saline (SAL), free clozapine (CZP) (25 mg/Kg i.p.), blank uncoated nanocapsules (BNC), clozapine-loaded uncoated nanocapsules (CNC) (25 mg/Kg i.p.), blank chitosan-coated nanocapsules (BCSN), clozapine-loaded chitosan-coated nanocapsules (CCSN) (25 mg/Kg i.p.), blank polyethyleneglycol-coated nanocapsules (BPEGN), clozapine-loaded polyethyleneglycol-coated nanocapsules (CPEGN) (25 mg/Kg i.p.). The animals received the formulation once a day for seven consecutive days and euthanized in the eighth day. After euthanasia, the brain was collected and homogenate was processed for further analysis. The histopathology showed less brain tissue damage in nanocapsules-treated groups. The lipid peroxidation and carbonylation of proteins showed a significant increase (p < 0.05) induced by CZP. CNC and CPEGN groups obtained a reduction membrane of lipids damage and nanocapsules-treated groups showed significant improvement protein damage. CZP was able to induce genetic oxidative damage, while the nanocapsules causing less damage to DNA. The findings show that different coatings can act protecting target tissues decreasing oxidative damage, suggesting that the drug when linked to different nanocapsules is able to mitigate the harmful effects of clozapine.
氯氮平,一种非典型抗精神病药物,能够改变氧化应激参数。众所周知,过量的活性物质在疾病病因中可能起关键作用,并且还会增强药物诱发的不良反应。纳米胶囊作为多种药物的载体已引起关注,随之可减少不良反应。本研究旨在评估用含氯氮平的纳米胶囊处理后的Wistar大鼠大脑中生物分子脂质、蛋白质和DNA的组织病理学及氧化损伤情况。该研究包括八组雄性Wistar大鼠(n = 6):生理盐水组(SAL)、游离氯氮平组(CZP)(腹腔注射25 mg/Kg)、空白未包衣纳米胶囊组(BNC)、载氯氮平未包衣纳米胶囊组(CNC)(腹腔注射25 mg/Kg)、空白壳聚糖包衣纳米胶囊组(BCSN)、载氯氮平壳聚糖包衣纳米胶囊组(CCSN)(腹腔注射25 mg/Kg)、空白聚乙二醇包衣纳米胶囊组(BPEGN)、载氯氮平聚乙二醇包衣纳米胶囊组(CPEGN)(腹腔注射25 mg/Kg)。动物连续七天每天接受一次制剂处理,并在第八天安乐死。安乐死后,收集大脑并制备匀浆用于进一步分析。组织病理学显示纳米胶囊处理组的脑组织损伤较少。脂质过氧化和蛋白质羰基化显示由CZP诱导显著增加(p < 0.05)。CNC组和CPEGN组脂质损伤膜减少,纳米胶囊处理组蛋白质损伤显著改善。CZP能够诱导遗传氧化损伤,而纳米胶囊对DNA的损伤较小。研究结果表明,不同的包衣可以起到保护靶组织、减少氧化损伤的作用,这表明与不同纳米胶囊结合的药物能够减轻氯氮平的有害影响。