da Silva Andréa Cristina Apolinário, Neves Juliana Kelle de Andrade Lemoine, Irmão João Inácio, Costa Vláudia Maria Assis, Souza Valdênia Maria Oliveira, de Medeiros Paloma Lys, da Silva Eliete Cavalcanti, de Lima Maria do Carmo Alves, Pitta Ivan da Rocha, Albuquerque Mônica Camelo Pessoa de Azevedo, Galdino Suely Lins
Laboratório de Planejamento e Síntese de Fármacos, Universidade Federal de Pernambuco, Avenida Professors Moraes Rego 1265, Cidade Universitária, Recife, PE, Brazil.
ScientificWorldJournal. 2012;2012:520524. doi: 10.1100/2012/520524. Epub 2012 May 1.
Previous studies conducted with the imidazolidinic derivative 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin-2-one (LPSF-PT05) show outstanding activity against adult Schistosoma mansoni worms in vitro. In the first phase of this study, S. mansoni-infected mice were treated, orally, with 100 mg/Kg of the LPSF-PT05 in three formulations: Tween 80 and saline solution, oil/water (70 : 30) emulsion, and solid dispersion with polyethylene glycol (PEG). In the second phase, three other doses of the LPSF-PT05 in PEG were tested: 3, 10, 30 mg/kg. These treatment regimens significantly reduced the number of recovered worms due to increases in the solubility of the compound in this formulation; the greatest reduction (70.5%) was observed at the dose of 100 mg/kg. There was no changes in the pattern of mature egg compared to immature eggs; however there was a significant increase in the number of dead eggs. Histopathological analysis of liver tissue showed changes in morphological aspects of the hepatic parenchyma with decrease exudative-productive hepatic granuloma stages, although we found no significant differences in IFN-γ, IL-4, IL-10, or NO production in response to the specific antigen SEA. The results show the derivative LPSF-PT05 to be a potential candidate in the etiological treatment of schistosomiasis with a possible dampening effect of the granulomatous process.
先前使用咪唑啉衍生物3-苄基-5-(4-氯-芳基偶氮)-4-硫代-咪唑啉-2-酮(LPSF-PT05)进行的研究表明,该化合物在体外对曼氏血吸虫成虫具有显著活性。在本研究的第一阶段,用三种制剂对感染曼氏血吸虫的小鼠进行口服治疗,剂量为100 mg/Kg的LPSF-PT05:吐温80和盐溶液、油/水(70 : 30)乳液以及与聚乙二醇(PEG)的固体分散体。在第二阶段,测试了PEG中另外三种剂量的LPSF-PT05:3、10、30 mg/kg。这些治疗方案显著减少了回收的蠕虫数量,这是由于该制剂中化合物的溶解度增加;在100 mg/kg剂量下观察到最大减少率(70.5%)。与未成熟卵相比,成熟卵的模式没有变化;然而,死卵数量显著增加。肝组织的组织病理学分析显示肝实质的形态学方面发生了变化,肝肉芽肿的渗出-增殖阶段减少,尽管我们发现针对特异性抗原SEA的IFN-γ、IL-4、IL-10或NO产生没有显著差异。结果表明,衍生物LPSF-PT05可能是血吸虫病病因治疗的潜在候选药物,对肉芽肿形成过程可能有抑制作用。