Targeting reactivated toxoplasmosis: therapeutic efficacy of the green-synthesized copper nanoparticles combined with pyrimethamine

ABSTRACT This investigation seeks to determine their potential efficacy in reducing parasite load and mitigating disease progression in immunocompromised hosts. The green synthesis of copper nanoparticles (CNPs) was performed using an extract from Rumex vesicarius . The chronic toxoplasmosis model was developed using the ME49 strain of Toxoplasma gondii . RT in the mice was achieved using dexamethasone (0.25 mg/kg) for 30 days. Then, mice were randomly assigned to 10 distinct groups, which were orally treated with CNP alone (10 and 20 mg/kg) and in combination with pyrimethamine (PM, 5 mg/kg) for 28 days. Next, parasite burden, spleen cell proliferation, and cytokine analysis, molecular analysis of inflammatory and apoptosis gene expression, oxidative/antioxidative biomarkers, and biochemical analysis were evaluated. CNP exhibits a uniform distribution and spherical morphology with an average diameter of 40 nm. CNP, mainly in combination with PM, significantly enhanced the survival rate in RT mice ( P < 0.001), whereas it markedly yielded the most substantial reduction in parasite burden across all organs assessed ( P < 0.001). The CNP 20 mg/kg + PM 5 mg/kg group demonstrated the highest increases in the gene expression of immune factors (3.78- to 5.79-fold change) ( P < 0.001), whereas it reduced the expression of pro-apoptotic markers ( P < 0.01). CNP + PM indicated a synergistic interaction in mitigating liver and kidney damage associated with reactivated toxoplasmosis. The combined administration of CNP and PM significantly decreased the parasitic load in cases of reactivated toxoplasmosis, concurrently augmenting antioxidant capacity and innate immune function. These results indicate that CNP holds potential as a valuable adjunctive therapy to enhance treatment efficacy in reactivated toxoplasmosis.