Insights on the therapeutic effect of quinolone-based compound, PPQ-8 plus Nitazoxanide, in chronic toxoplasmosis murine model

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 and anti-Toxoplasma drug may induce a convenient therapeutic effect on chronic toxoplasmosis Objectives: To evaluate the effect of quinolone-based compound (PPQ-8) combined with nitazoxanide 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 treated with pyrimethamine and sulfadiazine (PYR/SDZ), other mice received PPQ-8 alone showed mild to moderate inflammation and mice received PPQ-8/NTZ had mild inflammation. Five mice from each group were sacrificed after the end of treatment (14 days) 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 parameters. The remaining 5 mice were monitored for 60 days to calculate survival rate for each group. Results: The number and size of Toxoplasma brain cysts were significantly decreased among all treated groups when compared with infected untreated group. Histopathological studies of brain sections of control mice showed severe inflammation, meanwhile, mice treated with PYR/SDZ had moderate inflammation and mice given PPQ-8 alone or combined with NTZ showed 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 the production of brain iNOS level, however, PYR/SDZ-treated group recorded a significant reduction in serum level of IFN-γ, and TNF-α and brain iNOS when compared with the infected untreated group. Conclusions: It was concluded that PPQ-8/NTZ has immunostimulatory effect with a synergistic effect, so can be a promising regimen used for treatment of chronic toxoplasmosis.