High Prophylactic Efficacy of Thymol Loaded Chitosan Nanoparticles for Controlling Acute Toxoplasmosis in Mice
-
Mohammad Amin Ghobadi
,
Hossein Mahmoudvand
,
Amal Khudair Khalaf
,
Fatemeh Azadbakht
,
Marzieh Rashidipour
,
Iraj Salimikia
Abstract
Background: Given the significant role of chitosan nanoparticles in medicine, the present study aimed to assess the in vivo efficacy of synthesized chitosan nanoparticles coated with thymol (CNCT) in combating Toxoplasma gondii infection.
Methods: Mice were administered CNCT orally at dosages ranging from 0.25 to 0.75 mg/kg/day for a duration of 14 days. Following this treatment, they were infected with T. gondii tachyzoites of the Rh strain to induce acute toxoplasmosis. Then, the mortality rate, parasite load, antioxidant activity, and the gene expression level of proinflammatory cytokines were evaluated.
Results: The dimensions of CNTN exhibit variability, with a mean size of 295 nm. The prophylactic administration of CNTN in mice infected with T. gondii resulted in a significant enhancement in survival rates and a considerable decrease in parasite load (P<0.001). The CNTN caused a significant decrease in malondialdehyde level, while a notable increase (P < 0.001) in the activity of the antioxidant enzymes. The feeding the mice infected with CNTN caused a meaningful elevation in the expression level of TNFα- and IL-1β (P<0.001). The biochemical analyses indicated no significant changes in the serum levels of liver and kidney function markers.
Conclusion: The recent study revealed that CNTN demonstrates promising in vivo effects against toxoplasmosis in murine models. These effects are attributed to its antioxidant properties and immunomodulatory capabilities, which increase specific pro-inflammatory cytokines without any noticeable signs of toxicity to liver and kidney function.
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12. Parsaei P, Bahmani M, Naghdi N, Asadi-Samani M, Rafieian-Kopaei M. A review of therapeutic and pharmacological effects of thymol. Der Pharm Lett. 2016;8(2):150-4.
13. Wang X, Hu Y, Zhang Z, Zhang B. The application of thymol-loaded chitosan nanoparticles to control the biodeterioration of cultural heritage sites. Journal of Cultural Heritage. 2022;53:206-11.
14. Mahmoudvand H, Tavakoli Kareshk A, Nabi Moradi M, et al. Efficacy and safety of Zataria multiflora Boiss essential oil against acute toxoplasmosis in mice. Iran J Parasitol. 2020;15(1):22-30.
15. Shakibaie M, Ezzatkhah F, Gabal E, et al. Prophylactic effects of biogenic selenium nanoparticles on acute toxoplasmosis: an in vivo study. Ann Med Surg (Lond). 2020;54:85-88.
16. Baghdadi HB, Albalawi AE, Shater AF, et al. Linalool‐zinc oxide nanocomposite controls Toxoplasma gondii infection through inhibiting inflammation, oxidative stress, and pathogenicity. J Basic Microbiol. 2024; 64(8):e2400039.
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18. Xu J, Song M, Fang Z, Zheng L, Huang X, Liu K. Applications and challenges of ultra-small particle size nanoparticles in tumor therapy. J Control Release. 2023;353:699-712.
19. Dolai J, Mandal K, Jana NR. Nanoparticle size effects in biomedical applications. ACS Appl Nano Material. 2021;4(7):6471-96.
20. Engstrom AM, Faase RA, Marquart GW, et al. Size-dependent interactions of lipid-coated gold nanoparticles: developing a better mechanistic understanding through model cell membranes and in vivo toxicity. Int J Nanomedicine. 2020; 15:4091-4104.
21. Teimouri A, Azami SJ, Keshavarz H, et al. Anti-Toxoplasma activity of various molecular weights and concentrations of chitosan nanoparticles on tachyzoites of RH strain. Int J Nanomedicine. 2018; 13:1341-51.
22. Etewa SE, El-Maaty DA, Hamza RS, et al. Assessment of spiramycin-loaded chitosan nanoparticles treatment on acute and chronic toxoplasmosis in mice. J Parasit Dis. 2018;42:102-113.
23. Norouzi M, Mamaghani AJ, Tabaei SJ, et al. Evaluation of the efficacy of chitosan nanoparticles based on rosuvastatin in the treatment of acute toxoplasmosis: an in vitro and in vivo study. Microb Pathog. 2024; 195:106897.
24. Oliveira CB, Meurer YS, Medeiros TL, et al. Anti-Toxoplasma activity of estragole and thymol in murine models of congenital and noncongenital toxoplasmosis. J Parasitol. 2016;102(3):369-76.
25. Jain K, Jain NK. Novel therapeutic strategies for treatment of visceral leishmaniasis. Drug Discov Today. 2013;18(23-24):1272-81.
26. Mota ML, Lobo LT, Costa JM, et al. In vitro and in vivo antimalarial activity of essential oils and chemical components from three medicinal plants found in northeastern Brazil. Planta Med. 2012;78(7):658-64.
27. Fujisaki R, Kamei K, Yamamura M, et al. In vitro and in vivo anti-plasmodial activity of essential oils, including hinokitiol. Southeast Asian J Trop Med Public Health. 2012;43(2):270-9.
28. Tanghort M, Chefchaou H, Mzabi A, et al. Oocysticidal effect of essential oils and their major components on Cryptosporidium baileyi and Cryptosporidium galli. Inter J Poultry Sci, 2019;18: 475-482.
29. Marchese A, Orhan IE, Daglia M, et al. Antibacterial and antifungal activities of thymol: A brief review of the literature. Food Chem. 2016;210:402-14.
30. Memar MY, Raei P, Alizadeh N, et al. Carvacrol and thymol: strong antimicrobial agents against resistant isolates. Rev Med Microbiol. 2017;28(2):63-8.
31. van de Crommenacker J, Richardson DS, Koltz AM, Hutchings K, Komdeur J. Parasitic infection and oxidative status are associated and vary with breeding activity in the Seychelles warbler. Proc Biol Sci. 2012;279(1733):1466-76.
32. Szewczyk-Golec K, Pawłowska M, Wesołowski R, et al. Oxidative stress as a possible target in the treatment of toxoplasmosis: perspectives and ambiguities. Int J Mol Sci. 2021;22(11):5705.
33. De Titto EH, Catterall JR, Remington JS. Activity of recombinant tumor necrosis factor on Toxoplasma gondii and Trypanosoma cruzi. J Immunol. 1986; 137(4): 1342–1345
34. Chang HR, Grau GE, Pechere JC. Role of TNF and IL-1 in infections with Toxoplasma gondii. Immunology. 1990; 69(1): 33–37.
35. Fielden MR, Kolaja KL. The role of early in vivo toxicity testing in drug discovery toxicology. Expert Opin Drug Saf. 2008;7(2):107-10.
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. Saadatnia G, Golkar M. A review on human toxoplasmosis. Scand J Infect Dis. 2012;44(11):805-14.
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. Montazeri M, Mehrzadi S, Sharif M, et al. Drug resistance in Toxoplasma gondii. Front Microbiol. 2018;9:2587.
7. Cheraghipour K, Masoori L, Ezzatkhah F, et al. Effect of chitosan on Toxoplasma gondii infection: A systematic review. Parasite Epidemiol Control. 2020;11:e00189.
8. Ezhilarasi PN, Karthik P, Chhanwal N, Anandharamakrishnan C. Nanoencapsulat-ion techniques for food bioactive components: a review. Food Biop Technol. 2013;6:628-47.
9. Jafari SM. An overview of nanoencapsula-tion techniques and their classification. Nanoencapsul Tech Food Nutrac Industr. 2017:1-34.
10. Aranaz I, Alcántara AR, Civera MC, Arias C, Elorza B, Heras Caballero A, Acosta N. Chitosan: An overview of its properties and applications. Polymers (Basel). 2021;13(19):3256.
11. Escobar A, Perez M, Romanelli G, Blustein G. Thymol bioactivity: A review focusing on practical applications. Arabian J Chem. 2020;13(12):9243-69.
12. Parsaei P, Bahmani M, Naghdi N, Asadi-Samani M, Rafieian-Kopaei M. A review of therapeutic and pharmacological effects of thymol. Der Pharm Lett. 2016;8(2):150-4.
13. Wang X, Hu Y, Zhang Z, Zhang B. The application of thymol-loaded chitosan nanoparticles to control the biodeterioration of cultural heritage sites. Journal of Cultural Heritage. 2022;53:206-11.
14. Mahmoudvand H, Tavakoli Kareshk A, Nabi Moradi M, et al. Efficacy and safety of Zataria multiflora Boiss essential oil against acute toxoplasmosis in mice. Iran J Parasitol. 2020;15(1):22-30.
15. Shakibaie M, Ezzatkhah F, Gabal E, et al. Prophylactic effects of biogenic selenium nanoparticles on acute toxoplasmosis: an in vivo study. Ann Med Surg (Lond). 2020;54:85-88.
16. Baghdadi HB, Albalawi AE, Shater AF, et al. Linalool‐zinc oxide nanocomposite controls Toxoplasma gondii infection through inhibiting inflammation, oxidative stress, and pathogenicity. J Basic Microbiol. 2024; 64(8):e2400039.
17. Mahmoudvand H, Tavakoli Oliaei R, Mirbadie SR, et al. Efficacy and safety of Bunium persicum (Boiss) to inactivate protoscoleces during hydatid cyst operations. Surg Infect (Lurchmt). 2016;17(6):713-9.
18. Xu J, Song M, Fang Z, Zheng L, Huang X, Liu K. Applications and challenges of ultra-small particle size nanoparticles in tumor therapy. J Control Release. 2023;353:699-712.
19. Dolai J, Mandal K, Jana NR. Nanoparticle size effects in biomedical applications. ACS Appl Nano Material. 2021;4(7):6471-96.
20. Engstrom AM, Faase RA, Marquart GW, et al. Size-dependent interactions of lipid-coated gold nanoparticles: developing a better mechanistic understanding through model cell membranes and in vivo toxicity. Int J Nanomedicine. 2020; 15:4091-4104.
21. Teimouri A, Azami SJ, Keshavarz H, et al. Anti-Toxoplasma activity of various molecular weights and concentrations of chitosan nanoparticles on tachyzoites of RH strain. Int J Nanomedicine. 2018; 13:1341-51.
22. Etewa SE, El-Maaty DA, Hamza RS, et al. Assessment of spiramycin-loaded chitosan nanoparticles treatment on acute and chronic toxoplasmosis in mice. J Parasit Dis. 2018;42:102-113.
23. Norouzi M, Mamaghani AJ, Tabaei SJ, et al. Evaluation of the efficacy of chitosan nanoparticles based on rosuvastatin in the treatment of acute toxoplasmosis: an in vitro and in vivo study. Microb Pathog. 2024; 195:106897.
24. Oliveira CB, Meurer YS, Medeiros TL, et al. Anti-Toxoplasma activity of estragole and thymol in murine models of congenital and noncongenital toxoplasmosis. J Parasitol. 2016;102(3):369-76.
25. Jain K, Jain NK. Novel therapeutic strategies for treatment of visceral leishmaniasis. Drug Discov Today. 2013;18(23-24):1272-81.
26. Mota ML, Lobo LT, Costa JM, et al. In vitro and in vivo antimalarial activity of essential oils and chemical components from three medicinal plants found in northeastern Brazil. Planta Med. 2012;78(7):658-64.
27. Fujisaki R, Kamei K, Yamamura M, et al. In vitro and in vivo anti-plasmodial activity of essential oils, including hinokitiol. Southeast Asian J Trop Med Public Health. 2012;43(2):270-9.
28. Tanghort M, Chefchaou H, Mzabi A, et al. Oocysticidal effect of essential oils and their major components on Cryptosporidium baileyi and Cryptosporidium galli. Inter J Poultry Sci, 2019;18: 475-482.
29. Marchese A, Orhan IE, Daglia M, et al. Antibacterial and antifungal activities of thymol: A brief review of the literature. Food Chem. 2016;210:402-14.
30. Memar MY, Raei P, Alizadeh N, et al. Carvacrol and thymol: strong antimicrobial agents against resistant isolates. Rev Med Microbiol. 2017;28(2):63-8.
31. van de Crommenacker J, Richardson DS, Koltz AM, Hutchings K, Komdeur J. Parasitic infection and oxidative status are associated and vary with breeding activity in the Seychelles warbler. Proc Biol Sci. 2012;279(1733):1466-76.
32. Szewczyk-Golec K, Pawłowska M, Wesołowski R, et al. Oxidative stress as a possible target in the treatment of toxoplasmosis: perspectives and ambiguities. Int J Mol Sci. 2021;22(11):5705.
33. De Titto EH, Catterall JR, Remington JS. Activity of recombinant tumor necrosis factor on Toxoplasma gondii and Trypanosoma cruzi. J Immunol. 1986; 137(4): 1342–1345
34. Chang HR, Grau GE, Pechere JC. Role of TNF and IL-1 in infections with Toxoplasma gondii. Immunology. 1990; 69(1): 33–37.
35. Fielden MR, Kolaja KL. The role of early in vivo toxicity testing in drug discovery toxicology. Expert Opin Drug Saf. 2008;7(2):107-10.
| Files | ||
| Issue | Vol 20 No 1 (2025) | |
| Section | Original Article(s) | |
| Keywords | ||
| Toxoplasmosis Nanomedicine Antioxidant Inflammation Mice | ||
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How to Cite
1.
Ghobadi MA, Mahmoudvand H, Khudair Khalaf A, Azadbakht F, Rashidipour M, Salimikia I. High Prophylactic Efficacy of Thymol Loaded Chitosan Nanoparticles for Controlling Acute Toxoplasmosis in Mice. Iran J Parasitol. 2025;20(1):100-110.
