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Anti-toxoplasmic effects of celecoxib alone and combined with spiramycin in experimental mice
Sawsan S Shendi1, Sahar M Selim1, Soraya A Sharaf1
1Department of Clinical and Molecular Parasitology, National Liver Institute, Menoufia University, Shebin El-Kom, Menoufia, Egypt.
Abstract:
Even though toxoplasmosis is a worldwide parasitic disease caused by Toxoplasma gondii (T. gondii), the available drugs used for the treatment of symptomatic toxoplasmosis have multiple drawbacks. So, there is a considerable need to discover new potential therapeutic agents. The current study aimed to assess the effect of celecoxib (CELE) alone or combined with spiramycin against chronic toxoplasmosis in experimentally infected mice. The study documented the reduction rate of T. gondii cysts in brain tissues and ultrastructural changes through transmission electron microscopy after treatment. We also investigated pathological changes in the brain, liver, lung, and spleen, as well as the expression of TGF-β, iNOS, and pSTAT-1 in brain tissues. Other markers for kidney function and serum levels of interleukins 10 and 12 were also assessed. The study reported a reduction rate of T. gondii brain cyst count of 32.9 % after CELE treatment, 71.7 % after spiramycin treatment, and 75.7 % after combined treatment. Furthermore, the CELE and spiramycin combination improved the ultrastructure and histopathology in brain tissues while decreasing TGF-β, iNOS, and pSTAT-1 expression. The combined therapy ameliorated the inflammation of the liver, lung, and spleen, upregulated the IL-12 level, reduced the IL-10 level, and was accompanied by a reduction in creatinine and urea in serum. In conclusion, CELE increased spiramycin therapeutic efficacy, and their combination showed a better response than spiramycin alone. Thus, the CELE combination with spiramycin represents a hopeful therapy against chronic toxoplasmosis.
Insights
Celecoxib (CELE) combined with spiramycin effectively reduced Toxoplasma gondii cysts in mice with chronic toxoplasmosis. This combination therapy offers a promising new treatment strategy for this widespread parasitic disease.
Area of Science:
- Parasitology
- Pharmacology
- Immunology
Background:
- Toxoplasmosis, caused by Toxoplasma gondii, is a global parasitic disease with limited effective treatments.
- Current therapies for toxoplasmosis exhibit significant drawbacks, necessitating the development of novel therapeutic agents.
Purpose of the Study:
- To evaluate the efficacy of celecoxib (CELE) alone and in combination with spiramycin against chronic toxoplasmosis in a murine model.
- To assess the impact of treatments on T. gondii cyst burden, tissue pathology, and specific molecular markers.
Main Methods:
- Experimentally infected mice were treated with CELE, spiramycin, or a combination.
- T. gondii cyst counts, brain ultrastructure, histopathology of multiple organs, and expression of TGF-β, iNOS, pSTAT-1, IL-10, and IL-12 were analyzed.
- Kidney function markers were also assessed.
Main Results:
- The CELE and spiramycin combination achieved a 75.7% reduction in T. gondii brain cysts, surpassing individual treatments.
- Combined therapy improved brain ultrastructure and histopathology, reduced inflammatory markers (TGF-β, iNOS, pSTAT-1), and modulated cytokine profiles (increased IL-12, decreased IL-10).
- Significant amelioration of inflammation in the liver, lung, and spleen, along with improved kidney function, was observed with the combination therapy.
Conclusions:
- Celecoxib enhances the therapeutic efficacy of spiramycin against chronic toxoplasmosis.
- The combination of CELE and spiramycin represents a potent and hopeful therapeutic strategy for managing chronic toxoplasmosis.
