RESUMO
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-ß, 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-ß, 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.
RESUMO
Despite being the initial choice for treating toxoplasmosis, sulfadiazine and pyrimethamine have limited effectiveness in eliminating the infection and were linked to a variety of adverse effects. Therefore, the search for new effective therapeutic strategies against toxoplasmosis is still required. The current work is the first research to assess the efficacy of spiramycin-loaded maltodextrin nanoparticles (SPM-loaded MNPs) as a novel alternative drug therapy against toxoplasmosis in a murine model. Fifty laboratory-bred Swiss albino mice were divided into five groups: normal control group (GI, n = 10), positive control group (GII, n = 10), orally treated with spiramycin (SPM) alone (GIII, n = 10), intranasal treated with SPM-loaded MNPs (GIV, n = 10), and orally treated with SPM-loaded MNPs (GV, n = 10). Cysts of Toxoplasma gondii ME-49 strain were used to infect the mice. Tested drugs were administered 2 months after the infection. Drug efficacy was assessed by counting brain cysts, histopathological examination, and measures of serum CD19 by flow cytometer. The orally treated group with SPM-loaded MNPs (GV) showed a marked reduction of brain cyst count (88.7%), histopathological improvement changes, and an increasing mean level of CD19 (80.2%) with significant differences. SPM-loaded MNPs showed potent therapeutic effects against chronic toxoplasmosis. Further research should be conducted to assess it in the treatment of human toxoplasmosis, especially during pregnancy.