Document Type : Original Article
Authors
1
Departments of Medical Parasitology, Faculties of Medicine,Mansoura University, Mansoura National University, Dakahlia Governorate, Egypt
2
Pharmaceutical Chemistry, and Pharmacy Delta University for Science and Technology ,Gamasa, Dakahlia Governorate, Egypt
3
Departments of Pharmaceutical Pathology ,Faculties of Medicine, Mansoura University, Delta University for Science, Dakahlia Governorate, Egypt
4
Departments of Medical Parasitology, Faculties of Medicine, Mansoura University, Mansoura ,Dakahlia Governorate, Egypt
5
Departments of Medical Parasitolog, Faculties of Medicine, Mansoura University, Mansoura National University, Mansoura, Dakahlia Governorate, Egypt
Abstract
Background: Recent studies showed promising results of the quinolone-based compound (PPQ-8)
against schistosomiasis and toxoplasmosis. It is hypothesized that combined treatment by PPQ-8 with an
anti-Toxoplasma drug may induce a convenient therapeutic effect on chronic toxoplasmosis.
Objective: To evaluate the effect of PPQ-8 combined with nitazoxanide (NTZ) on chronic experimental
toxoplasmosis.
Material and Methods: After being infected for three months with ME49 T. gondii, forty female Swiss
albino mice were randomly split into four equal groups. In comparison to untreated group, mice were
treated with pyrimethamine and sulfadiazine (PYR/SDZ), PPQ-8 alone or combined with nitazoxanide
(PPQ-8/NTZ). Five mice from each group were sacrificed after the end of treatment (14 d) to evaluate
drug efficacy using parasitological (brain cyst count and size), histopathological examination of brain
tissues, measurement of brain inducible nitric oxide synthase (iNOS) activity and immunological (IFN-γ
and TNF-α) parameters. The remaining 5 mice were monitored for 60 days to calculate survival time for
each group.
Results: The number and size of brain cysts were significantly decreased among all treated groups when
compared with control infected untreated group. Histopathological studies of brain sections of control
mice showed severe inflammation, mice treated with PYR/SDZ had moderate inflammation, those treated
with PPQ-8 alone showed mild to moderate inflammation, and those receiving PPQ-8/NTZ had mild
inflammation. Treatment with PPQ-8, and PPQ-8/NTZ induced an increase in serum level of IFN-γ, and
reduction in the level of TNF-α as well as raised production of brain iNOS level. Treatment with PYR/SDZrecorded
a significant reduction in serum level of IFN-γ, TNF-α and brain iNOS when compared with the
infected untreated group.
Conclusion: When combined with NTZ, PPQ-8 showed a promising regimen for treatment of chronic
toxoplasmosis due to its synergistic effect. Combined treatment exhibited mild inflammation, increased
levels of IFN-γ and iNOS, and decreased TNF-α production.
Keywords
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