Study of the activity of 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin-2-one against Schistosomiasis mansoni in mice

Abstract

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.

Figure 1

IFN-γ (a), IL-4 (b), and nitric oxide (c) production by spleen cells after treatment of S. mansoni-infected mice with LPSF-PT05-PEG. *P < 0.001 in comparison with control.

Figure 2

Photomicrographs of granuloma stage in the livers of mice infected by S. mansoni. (a) Infected control exhibiting exudative-productive stage granulomas (arrows) with a mature, viable egg in the center of the fibrocellular granulomas. (b) LPSF-PT05-PEG (3 mg/kg per day); micrographs show well-circumscribed small fibrocellular granulomas and marked ovum degeneration (asterisks). (c) LPSF-PT05-PEG (10 mg/kg per day); productive (arrow) and involutional (asterisk) granulomas stage. (d) LPSF-PT05-PEG (30 mg/kg per day). (e) LPSF-PT05-PEG (100 mg/kg per day) involutional stage granulomas (asterisks). H&E, micrographs are at 100x magnification.