Anti-toxoplasmic effects of celecoxib alone and combined with spiramycin in experimental mice

• Published in: Acta tropica Vol. 260; p. 107448
• Main Authors: Shendi, Sawsan S, Selim, Sahar M, Sharaf, Soraya A, Gouda, Marwa A, Sallam, Hebatallah M, Sweed, Dina M, Shafey, Dalia A
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-12-2024
• Subjects: Celecoxib; Cytokines; iNOS; Mice; pSTAT-1; TGF-β; Toxoplasma gondii; T. gondii; NO; TBRI; BBB; Cytokines; CELE; %; H&E; NSAID; AIDs; NLI; Celecoxib; MIF; SD; pSTAT-1; Toxoplasma gondii; ANOVA; IRB; X; iNOS; TGF-β; Mice; TEM; cytokines; mice
• ISSN: 0001-706X; 1873-6254; 1873-6254
• DOI: 10.1016/j.actatropica.2024.107448

•Celecoxib was effective against chronic toxoplasmosis, mainly when combined with spiramycin.•Celecoxib and spiramycin treatment decreased the mortality rate of infected mice from 10 % to 0.0 %.•Celecoxib and spiramycin treatment caused improvement in neurocyte ultrastructure.•Celecoxib and spiramycin combination caused an immunomodulatory effect and increased IL-12 from 17.43 to 30.15.•Brain tissues decreased immunohistochemical expression H. scores of TGF-β from 123 to 50, iNOS from 106.5 to 51, and pSTAT-1 from 136 to 44.4 after celecoxib and spiramycin treatment.
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.
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