The efficacy of resveratrol and nitazoxanide combination therapy in a murine model of chronic toxoplasmosis.

Toxoplasmosis is a global parasitic disease that can affect the central nervous system, causing severe complications. Introducing new agents that are safe during pregnancy and more effective for chronic toxoplasmosis is essential. This study investigated the effects of combined treatments with resveratrol, nitazoxanide, and spiramycin in chronic toxoplasmosis. Fifty-four Swiss albino mice were distributed into nine groups: Group 1, non-infected control; Group 2, infected non-treated control; Group 3, infected resveratrol-treated; Group 4, infected nitazoxanide-treated; Group 5, infected spiramycin-treated; Group 6, infected resveratrol and nitazoxanide-treated; Group 7, infected resveratrol and spiramycin-treated; Group 8, infected resveratrol, nitazoxanide, and spiramycin-treated; and Group 9, infected half-dose resveratrol, nitazoxanide, and spiramycin-treated. Effectiveness was evaluated by counting brain tissue cysts, histopathological examination of liver and brain tissues, immunohistochemical analysis of brain CD8+ T expression, biochemical measurement of serum IFN-γ and tissue MDA levels, and molecular assays for iNOS and BAX gene expression. The data demonstrated that adding resveratrol to spiramycin significantly reduced brain tissue cyst load, improved underlying tissue pathology, reduced brain CD8+ T expression, and lowered serum IFN-γ, tissue MDA, iNOS, and BAX gene levels in the liver, with elevated MDA, iNOS, and BAX gene levels in the brain. These results were enhanced by adding nitazoxanide to the resveratrol and spiramycin combination. It can be concoluded that co-administration of resveratrol and nitazoxanide can synergistically enhance the therapeutic effect of spiramycin in chronic toxoplasmosis.