Document Type : Original Article
Authors
1
Department of Parasitology, Faculty of Medicine, Benha University, Benha, Qalubyia, Egypt
2
Medical Parasitology Department, Research Institue of Ophthalmology, Giza, Egypt
3
Applied Organic Chemistry Department, Chemical Industries Research Institute, National Research Centre, Dokki, Giza, Egypt
4
Department of Zoonotic Diseases, National Research Centre, Dokki, Giza, Egypt
Abstract
Because Toxoplasma gondii is a parasite with several developmental stages and strains, anti-Toxoplasma medications must be efficient for various stages and strains. The commonly used drugs need long treatment periods and have hazardous side effects. Combining therapies may decrease the pharmaceutical dosages while preserving therapeutic effects and minimizing toxicity. This study evaluated the efficacy of combining spiramycin and metronidazole with testosterone/progesterone and the combination loaded on Zeolitic imidazolate frameworks (ZIF-8) nanoparticles in treating chronic toxoplasmosis in animal models. Mice were orally infected by brain suspension containing Toxoplasma gondii cysts. They were sorted into female and male groups, and each group was then divided into five subgroups: negative control (uninfected), positive control (infected untreated), treated with spiramycin and metronidazole, treated with spiramycin and metronidazole in combination with testosterone/progesterone, and treated with the combination-loaded ZIF-8 nanoparticles. Tested compounds' efficacy was determined by parasitological assessment of parasite load in the brain, Toxoplasma DNA quantification in brain tissues using real-time PCR, and histopathological evaluation. Treatment of infected mice with spiramycin and metronidazole in combination with testosterone or progesterone significantly decreased the parasite burden. Moreover, mice treated with the drug combination carried on ZIF-8 showed a marked decrease in parasitic load versus the other groups. All treated groups showed a reduction in Toxoplasma DNA concentrations in brain tissues, with significant variation compared to positive controls. Likewise, combo therapy successfully cured the histopathological alterations in the infected mice's brains. In conclusion, sex hormones can modulate Toxoplasma infection, and their loading on ZIF-8 nanoparticles increased anti-toxoplasmic effect.
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