Green Synthesized Gold Nanoparticles Ameliorate the Toxoplasma gondii Infection in Immunosuppressed Mice
Abstract
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.
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19. Saadatmand M, Al-Awsi GR, Alanazi AD, et al. Green synthesis of zinc nanoparticles using Lavandula angustifolia Vera. Extract by microwave method and its prophylactic effects on Toxoplasma gondii infection. Saudi J Biol Sci. 2021;28(11):6454-60.
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21. Sasidharan S, Saudagar P. Gold and silver nanoparticles functionalized with 4’, 7-dihydroxyflavone exhibit activity against Leishmania donovani. Acta Trop. 2022;231:106448.
22. Adeyemi OS, Murata Y, Sugi T, Kato K. Inorganic nanoparticles kill Toxoplasma gondii via changes in redox status and mitochondrial membrane potential. Int J Nanomedicine. 2017;12:1647-1661.
23. Barabadi H, Honary S, Ali Mohammadi M, et al. Green chemical synthesis of gold nanoparticles by using Penicillium aculeatum and their scolicidal activity against hydatid cyst protoscolices of Echinococcus granulosus. Environ Sci Pollut Res Int. 2017;24(6):5800-5810.
24. Kar PK, Murmu S, Saha S, Tandon V, Acharya K. Anthelmintic efficacy of gold nanoparticles derived from a phytopathogenic fungus, Nigrospora oryzae. PloS One. 2014;9(1):e84693.
25. Cerutti A, Blanchard N, Besteiro S. The bradyzoite: a key developmental stage for the persistence and pathogenesis of toxoplasmosis. Pathogens. 2020;9(3):234.
26. Selseleh M, Modarressi MH, Shojaee S, et al. Brain tissue cysts in infected mice with RH-strain of Toxoplasma gondii and evaluation of BAG1 and SAG1 genes expression. Iran J Parasitol. 2013;8(1):40-6.
27. Szewczyk-Golec K, Pawłowska M, Wesołowski R, Wróblewski M, Mila-Kierzenkowska C. Oxidative Stress as a Possible Target in the Treatment of Toxoplasmosis: Perspectives and Ambiguities. Int J Mol Sci. 2021; 22(11):5705.
28. Barathmanikanth S, Kalishwaralal K, Sriram M, et al. Anti-oxidant effect of gold nanoparticles restrains hyperglycemic conditions in diabetic mice. J Nanobiotechnology. 2010;8:16.
29. Jafari MM, Tabrizi ZA, Dayer MS, et al. Immune system roles in pathogenesis, prognosis, control, and treatment of Toxoplasma gondii infection. Int Immunopharmacol. 2023;124:110872.
30. Khan IA, Moretto M. Immune responses to Toxoplasma gondii. Curr Opin Immunol. 2022;77:102226.
31. Kang KN, Choi IU, Shin DW, Lee YH. Cytokine and antibody responses of reactivated murine toxoplasmosis upon administration of dexamathasone. Korean J Parasitol. 2006;44(3):209-19.
32. Huang H, Liu R, Yang J, et al. Gold Nanoparticles: Construction for Drug Delivery and Application in Cancer Immunotherapy. Pharmaceutics. 2023;15(7):1868.
33. Reshi MS, Shrivastava S, Jaswal A, Sinha N, Uthra C, Shukla S. Gold nanoparticles ameliorate acetaminophen induced hepato-renal injury in rats. Exp Toxicol Pathol. 2017;69(4):231-240.
2. Elsheikha HM, Marra CM, Zhu XQ. Epidemiology, pathophysiology, diagnosis, and management of cerebral toxoplasmosis. Clin Microbiol Rev. 2020;34(1): e00115-19.
3. Biesiada G, Kalinowska-Nowak A, Czepiel J, Mach T. Toxoplasmosis--epidemiology, clinical manifestation and infection in pregnant women. Przegl Lek. 2006;63(2):97-9.
4. Teimouri A, Goudarzi F, Goudarzi K, Alimi R, Sahebi K, Foroozand H, Keshavarz H. Toxoplasma gondii Infection in Immunocompromised Patients in Iran (2013-2022): A Systematic Review and Meta-Analysis. Iran J Parasitol. 2022;17(4):443-457.
5. Dunay IR, Gajurel K, Dhakal R, Liesenfeld O, Montoya JG. Treatment of toxoplasmosis: historical perspective, animal models, and current clinical practice. Clin Microbiol Rev. 2018;31(4): e00057-17.
6. Cheraghipour K, Masoori L, Ezzatkhah F, et al. Effect of chitosan on Toxoplasma gondii infection: A systematic review. Parasite Epidemiol Contr. 2020;11:e00189.
7. Zhang Y, Bi J, Huang J, Tang Y, Du S, Li P. Exosome: A Review of Its Classification, Isolation Techniques, Storage, Diagnostic and Targeted Therapy Applications. Int J Nanomedicine. 2020;15:6917-6934.
8. Elahi N, Kamali M, Baghersad MH. Recent biomedical applications of gold nanoparticles: A review. Talanta. 2018;184:537-56.
9. Hammami I, Alabdallah NM. Gold nanoparticles: Synthesis properties and applications. J King Saud Univ Sci. 2021;33(7):101560.
10. Santhosh PB, Genova J, Chamati H. Green synthesis of gold nanoparticles: An eco-friendly approach. Chemistry. 2022;4(2):345-69.
11. Hashemi-Hafshejani S, Amani A, Azami SJ, et al. Nanoemulsion of spiramycin against tachyzoites of Toxoplasma gondii, RH strain: preparation, toxicology, and efficacy studies. Iran J Public Health. 2023;52(7):1495.
12. Goudarzi F, Jajarmi V, Shojaee S, Mohebali M, Keshavarz H. Formulation and evaluation of atovaquone-loaded macrophage-derived exosomes against Toxoplasma gondii: in vitro and in vivo assessment. Microbiol Spectr. 2024;12(1):e0308023.
13. Khaledi A, Meskini M. A Systematic Re-view of the Effects of Satureja Khuzestanica Jamzad and Zataria Multiflora Boiss against Pseudomonas Aeruginosa. Iran J Med Sci. 2020;45(2):83-90.
14. Sidorowicz A, Margarita V, Fais G, et al. Characterization of nanomaterials synthesized from Spirulina platensis extract and their potential antifungal activity. PLoS One. 2022;17(9):e0274753.
15. Maqbool Q, Yigit N, Stöger-Pollach M, et al. Operando monitoring of a room temperature nanocomposite methanol sensor. Catal Sci Technol. 2022;13(3):624-636.
16. Rehg JE, Hancock ML, Woodmansee DB. Characterization of a dexamethasonetreated rat model of cryptosporidial infection. J Infect Dis. 1988;158(6): 1406e1407.
17. Mahmoudvand H, Ziaali N, Ghazvini H, et al. Toxoplasma gondii infection promotes neuroinflammation through cytokine networks and induced hyperalgesia in BALB/c mice. Inflammation. 2016;39:405-12.
18. Baghdadi HB, Albalawi AE, Shater AF, Almohammed H, Alanazi AD. Linalool‐zinc oxide nanocomposite controls Toxoplasma gondii infection through inhibiting inflammation, oxidative stress, and pathogenicity. J Basic Microbiol. 2024;64(8):e2400039.
19. Saadatmand M, Al-Awsi GR, Alanazi AD, et al. Green synthesis of zinc nanoparticles using Lavandula angustifolia Vera. Extract by microwave method and its prophylactic effects on Toxoplasma gondii infection. Saudi J Biol Sci. 2021;28(11):6454-60.
20. Mahmoudvand H, Kareshk AT, Moradi MN, et al. Efficacy and safety of Zataria multiflora Boiss essential oil against acute toxoplasmosis in mice. Iran J Parasitol. 2020;15(1):22-30.
21. Sasidharan S, Saudagar P. Gold and silver nanoparticles functionalized with 4’, 7-dihydroxyflavone exhibit activity against Leishmania donovani. Acta Trop. 2022;231:106448.
22. Adeyemi OS, Murata Y, Sugi T, Kato K. Inorganic nanoparticles kill Toxoplasma gondii via changes in redox status and mitochondrial membrane potential. Int J Nanomedicine. 2017;12:1647-1661.
23. Barabadi H, Honary S, Ali Mohammadi M, et al. Green chemical synthesis of gold nanoparticles by using Penicillium aculeatum and their scolicidal activity against hydatid cyst protoscolices of Echinococcus granulosus. Environ Sci Pollut Res Int. 2017;24(6):5800-5810.
24. Kar PK, Murmu S, Saha S, Tandon V, Acharya K. Anthelmintic efficacy of gold nanoparticles derived from a phytopathogenic fungus, Nigrospora oryzae. PloS One. 2014;9(1):e84693.
25. Cerutti A, Blanchard N, Besteiro S. The bradyzoite: a key developmental stage for the persistence and pathogenesis of toxoplasmosis. Pathogens. 2020;9(3):234.
26. Selseleh M, Modarressi MH, Shojaee S, et al. Brain tissue cysts in infected mice with RH-strain of Toxoplasma gondii and evaluation of BAG1 and SAG1 genes expression. Iran J Parasitol. 2013;8(1):40-6.
27. Szewczyk-Golec K, Pawłowska M, Wesołowski R, Wróblewski M, Mila-Kierzenkowska C. Oxidative Stress as a Possible Target in the Treatment of Toxoplasmosis: Perspectives and Ambiguities. Int J Mol Sci. 2021; 22(11):5705.
28. Barathmanikanth S, Kalishwaralal K, Sriram M, et al. Anti-oxidant effect of gold nanoparticles restrains hyperglycemic conditions in diabetic mice. J Nanobiotechnology. 2010;8:16.
29. Jafari MM, Tabrizi ZA, Dayer MS, et al. Immune system roles in pathogenesis, prognosis, control, and treatment of Toxoplasma gondii infection. Int Immunopharmacol. 2023;124:110872.
30. Khan IA, Moretto M. Immune responses to Toxoplasma gondii. Curr Opin Immunol. 2022;77:102226.
31. Kang KN, Choi IU, Shin DW, Lee YH. Cytokine and antibody responses of reactivated murine toxoplasmosis upon administration of dexamathasone. Korean J Parasitol. 2006;44(3):209-19.
32. Huang H, Liu R, Yang J, et al. Gold Nanoparticles: Construction for Drug Delivery and Application in Cancer Immunotherapy. Pharmaceutics. 2023;15(7):1868.
33. Reshi MS, Shrivastava S, Jaswal A, Sinha N, Uthra C, Shukla S. Gold nanoparticles ameliorate acetaminophen induced hepato-renal injury in rats. Exp Toxicol Pathol. 2017;69(4):231-240.
| Files | ||
| Issue | Vol 21 No 2 (2026) | |
| Section | Original Article(s) | |
| Keywords | ||
| Toxoplasmosis Immunosuppression Nanomedicine Bradyzoites | ||
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How to Cite
1.
Masoori L, Majeed Khazaal R, Rashidipour M, Sepahvand M, Mahmoudvand H. Green Synthesized Gold Nanoparticles Ameliorate the Toxoplasma gondii Infection in Immunosuppressed Mice. Iran J Parasitol. 2026;21(2):174-184.
