Tehran University of Medical Sciences Iranian Journal of Parasitology 1735-7020 21 2 2026 07 12 174 184 Leila Masoori Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran Ruaa Majeed Khazaal Department of Medical Laboratory Techniques, Nasiriyah Technical Institute, Southern Technical University, Nasiriyah, Iraq Marzieh Rashidipour Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran Maryam Sepahvand Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran Hossein Mahmoudvand Hepatitis Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran 2025 09 14 2026 07 12 Background: In immunocompromised individuals, Toxoplasma gondii infection can disseminate rapidly, causing severe cerebral and visceral complications. This study aimed to synthesize gold nanoparticles (AuNPs) via green synthesis and evaluate their therapeutic efficacy and mechanisms in immunosuppressed murine models of toxoplasmosis. Methods: Mice were immunosuppressed using dexamethasone prior to infection with the Tehran strain of T. gondii. AuNPs were administered orally at 0.5 and 1 mg/kg, alone or combined with pyrimethamine (PYR; 10 mg/kg), in a 0.2 mL volume for 14 days. Survival rates were monitored daily. Brain cyst number and size were assessed microscopically. Oxidative stress markers, cytokine levels, and bradyzoite surface antigen 1 (BAG1) gene expression were analyzed by real-time PCR. Results: Synthesized AuNPs exhibited cubic morphology with an average size of 20–30 nm. Combined AuNPs–PYR treatment significantly improved survival and reduced brain cyst burden (P=0.001). Treatment markedly decreased malondialdehyde (MDA) levels while enhancing glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity (P<0.01). Gene expression analysis demonstrated downregulation of BAG1 and IL-4 (<1.3-fold) alongside upregulation of IFN-γ and IL-12 (>4-fold). Hepatic and renal biomarkers were also significantly improved. Conclusion: AuNPs, particularly in combination with PYR, demonstrate significant efficacy against toxoplasmosis in immunosuppressed murine models. Clinical trials are warranted to further assess the safety and therapeutic potential of this combination approach. https://ijpa.tums.ac.ir/index.php/ijpa/article/view/4763 https://ijpa.tums.ac.ir/index.php/ijpa/article/download/4763/1492