RESUMO
Schistosomicidal activity of six phthalimido-thiazoles derivatives with substitutions at the position three of the thiazole ring were analyzed in an experimental model. The substituents biphenyl (2i) and 2- naphthyl (2j) at a concentration of 80 µg/mL caused 100% mortality of the parasite in culture after 24 h and 48 h respectively. An evaluation of ultrastructural parasites showed damage in the tegument, formation of bubbles and partial destruction of the tubercles. The in vivo anti-parasitic activity with the derivate 2i was performed by administering it orally and intraperitoneally in a 400 mg/kg/5days regimen. Decreases in the number of eggs in the gut (45.1%) and a reduction of the percentage of mature (23.7%) and increased unviable (53.8%) eggs were observed. Our results also showed a reduction in the number of recovered worms after treatment with 2i (oral administration: 81, 25%). The results demonstrated that the prototypes which were tested had a significant anti-schistosomal effect against S. mansoni, suggesting that these derivatives are promising candidates for further research into the chemotherapy of schistosomiasis.
Assuntos
Antiprotozoários/uso terapêutico , Ftalimidas/química , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/tratamento farmacológico , Tiazóis/farmacologia , Animais , Antiprotozoários/farmacologia , Feminino , Técnicas In Vitro , Masculino , Camundongos , Contagem de Ovos de Parasitas , Schistosoma mansoni/isolamento & purificação , Espectroscopia de Infravermelho com Transformada de Fourier , Tiazóis/químicaRESUMO
Liver diseases are a major health problem worldwide leading to high mortality rates and causing a considerable economic burden in many countries. Cellular therapies as potential treatments for liver diseases have proven beneficial in most of the conditions. In recent years, studies involving therapy with bone marrow cells have been implemented to promote liver regeneration and to reduce hepatic fibrosis, however identifying the cell population present in the bone marrow that is responsible for hepatic improvement after therapy is still necessary. The aim of the present study was the evaluation of the therapeutic efficacy of monocytes obtained from bone marrow in fibrosis resulting from S. mansoni infection in C57BL/6 mice. Monocytes were isolated by immunomagnetic separation and administered to the infected animals. The effects of treatment were evaluated through morphometric, biochemical, immunological and molecular analyzes. Monocyte therapy promoted reduction of liver fibrosis induced by S. mansoni infection, associated with a decrease in production of inflammatory and pro-fibrogenic mediators. In addition, monocyte infusion caused downregulation of factors associated with the M1 activation profile, as well as upregulation of M2reg markers. The findings altogether reinforce the hypothesis that the predominance of M2reg macrophages, producers of immunosuppressive cytokines, may favor the improvement of hepatic fibrosis in a preclinical model, through fibrous tissue remodeling, modulation of the inflammatory response and fibrogenesis.
Assuntos
Transferência Adotiva/métodos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Cirrose Hepática/terapia , Regeneração Hepática , Monócitos/transplante , Schistosoma mansoni/patogenicidade , Esquistossomose mansoni/terapia , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/imunologia , Diferenciação Celular , Citocinas/genética , Citocinas/imunologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Fígado/imunologia , Fígado/parasitologia , Fígado/patologia , Cirrose Hepática/imunologia , Cirrose Hepática/parasitologia , Cirrose Hepática/patologia , Macrófagos/citologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/citologia , Monócitos/imunologia , Schistosoma mansoni/crescimento & desenvolvimento , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/parasitologia , Esquistossomose mansoni/patologiaRESUMO
Schistosomiasis is a major public health problem worldwide, especially in poor communities. Praziquantel is currently the only drug available to treat schistosomiasis and it shows low efficacy against schistosomula and juveniles stages of Schistosoma mansoni, allowing lower cure rate in areas with high endemicity. There is an urgent need to identify new antischistosomal drugs. Previous works identified phthalimido-thiazoles as privileged structures acting as schistossomicidal agent. In this way, a phthalimido-thiosemicarbazide intermediate and eight phthalimido-thiazoles derivatives were evaluated concerning the in vitro antischistosomal activity compounds in adult phase of Schistosoma mansoni and examined alterations on the tegumental surface. The results revealed that compounds 2f, 2â¯l and 2â¯m caused significant mortality in adult worms at concentrations range of 20⯵g/mL to 100⯵g/mL. These compounds were also selected in view to verify the activity against the schistosomula. Compound 2â¯m promoted 100% of mortality of larval forms until doses of 2.5⯵g/mL within 48â¯h. In addition, when compound 2â¯m was administered orally at dose of 200â¯mg/kg for 5 consecutive days to the infected mouse with adult schistosomes, a reduction in the parasite burden was observed. Furthermore, scanning electron microscopy revealed that compound 2â¯m kill the parasite by tegumental damage and bubbles generation.