Fe3O4@Bio-MOF Nanoparticles Combined with Artemisinin, Glucantime®, or Shark Cartilage Extract on Iranian Strain of Leishmania major (MRHO/IR/75/ER): An In-Vitro and In-Vivo Study
Background: In the present study, we examined the effects of Fe3O4@bio-MOF nanoparticle (Nano-FO) plus artemisinin (Art) and glucantime (Glu) or shark cartilage extract (ShCE) on Leishmania major in vitro and in vivo.
Methods: This experimental study was conducted at the laboratory of Department of Parasitology, Tarbiat Modares University, Tehran, Iran during 2016-2017. The promastigote and amastigote assays were performed were conducted at the presence of 3.12- 400 µg/mL of the drug combinations. According to in vitro IC50 results, the combinations of 12.5µg/mL Nano-FO with 25 µg/mL Art as well as 200 µg/mL Glu and 0.5 mL of 20 mg/kg of ShCE were used to treat BALB/c mice. During and at the end of the treatment, the lesion sizes were measured. Parasite loads, cytokine levels were evaluated at the end of the treatment.
Results: The IC50 of Fe3O4@bio-MOF-Artemisinin (Nano-FO/Art), Fe3O4@bio-MOF-Glucantime (Nano-FO/Glu), and Fe3O4@bio-MOF-Shark cartilage extract (Nano-FO/ShCE) on promasitigotes were 12.58±0.12, 235±0.17, and 18.54±0.15, respectively. These results on amastigotes were 10.32±0.01, 187±0.03, and 338±0.07 µg/mL, respectively. The apoptosis percentage of these combinations were 32.54%, 20.59%, and 15.68% in promastigotes and 15.68%, 12.84%, and 3.51% in infected macrophages, respectively with no toxicity on uninfected macrophages. In vivo results showed that the size of lesions significantly decreased against all drugs combinations, but Nano-FO/Art combination with Selectivity Index of 23.62 value was safe, and more effective on healing of lesions than other drugs combinations (P=0.003).
Conclusion: This study suggested that Nano-FO/Art combination can be considered as an anti-leishmania combination therapy in CL induced by L. major.
2. Sharma M, Shaikh N, Yadav S, et al. A systematic reconstruction and constraint-based analysis of Leishmania donovani metabolic network: identification of potential antileishmanial drug targets. Mol Biosyst. 2017;13(5):955-969.
3. World Health Organisation. Leishmaniaisis. https://www.who.int/data/gho/data/themes/topics/topic-details/GHO/leishmaniasis
4. Holakouie-Naieni K, Mostafavi E, Boloorani AD, et al. Spatial modeling of cutaneous leishmaniasis in Iran from 1983 to 2013. Acta Trop. 2017;166:67-73.
5. Mohtasebi S, Mohebali M, Elikaee S, et al. In vitro and in vivo anti-parasitic activity of biogenic antimony sulfide nanoparticles on Leishmania major (MRHO/IR/75/ER). Parasitol Res. 2019;118(9):2669-2678.
6. Alvar J, Croft S, Olliaro P. Chemotherapy in the treatment and control of leishmaniasis. Adv Parasitol. 2006;61:223-224.
7. Faleiro RJ, Kumar R, Bunn PT, et al. Combined Immune Therapy for the Treatment of Visceral Leishmaniasis. PLoS Negl Trop Dis. 2016;10(2):e0004415.
8. Ebrahimzade E, Mohebali M, Shayan P, et al. Investigation of the antimicrobial activity of a short cationic peptide against promastigote and amastigote forms of Leishmania major (MHRO/IR/75/ER): An in vitro study. Exp Parasitol. 2019;196:48-54.
9. Beheshti N, Soflaei S, Shakibaie M, et al. Efficacy of biogenic selenium nanoparticles against Leishmania major: in vitro and in vivo studies. J Trace Elem Med Biol. 2013; 27(3):203-207.
10. Abazari R, Mahjoub AR, Molaie S, et al. The effect of different parameters under ultrasound irradiation for synthesis of new nanostructured Fe3O4@ bio-MOF as an efficient anti-leishmanial in vitro and in vivo conditions. Ultrason Sonochem.2018;43:248-261.
11. Anderson SD, Gwenin VV, Gwenin CD. Magnetic Functionalized Nanoparticles for Biomedical, Drug Delivery and Imaging Applications. Nanoscale Res Lett.2019 ;14(1):188.
12. Mathew TV, Kuriakose S. Studies on the antimicrobial properties of colloidal silver nanoparticles stabilized by bovine serum albumin. Colloids Surf B Biointerfaces.2013; 101:14–8.
13. Khatami M, Alijani H, Sharifi I, et al. Leishmanicidal activity of biogenic Fe3O4 nanoparticles. Sci Pharm. 2017; 85(4):36.
14. Sen R, Chatterjee M. Plant derived therapeutics for the treatment of Leishmaniasis. Phytomedicine. 2011;18(12):1056-1069.
15. Molaie S , Ghaffarifar F, Hasan Z.M, et al. Enhancement effect of Artemisinin with Glucantime and Shark Cartilage extract on the killing factors and apoptosis of Leishmania infantum in vitro condition. Iran J Pharm Res. 2019;18 (2):887-902.
16. Davis PF, He Y, Furneaux RH, et al. Inhibition of angiogenesis by oral ingestion of powdered shark cartilage in a rat model. Microvasc Res.1997; 54(2):178-182.
17. Merly L. Immunomodulation by Shark Cartilage Extracts. Florida International University FIU Digital Commons. 2011; 35-37.
18. Molaie S , Ghaffarifar F, Dalimi A, et al. Evaluation of synergistic therapeutic effect of shark cartilage extract with artemisinin and glucantime on visceral leishmaniasis in BALB/c mice. Iran J Basic Med Sci. 2019;22(2):146–153.
19. Ghaffarifar F, Heydari FE, Dalimi A, et al. Evaluation of apoptotic and antileishmanial activities of Artemisinin on promastigotes and BALB/C mice infected with Leishmania major. Iran J Parasitol. 2015;10(2):258-67.
20. Feyzi R, Hassan ZM, Mostafaie A. Modulation of CD4+ and CD8+ tumor infiltrating lymphocytes by a fraction isolated from shark cartilage: shark cartilage modulates anti-tumor immunity. Int Immunopharmacol. 2003;3(7):921-926.
21. Ku HK, Lim HM, Oh KH, et al. Interpretation of protein quantitation using the Bradford assay: comparison with two calculation models. Anal biochem. 2013; 434(1):178-180.
22. Ulbricht C, Hammerness P, Ulbricht C, et al. Shark cartilage monograph: A clinical decision support tool. J Herb Pharmacother. 2002; 2(2):71-93.
23. Jabini R, Jaafari MR, Hasani FV, et al. Effects of combined therapy with silymarin and glucantime on leishmaniasis induced by Leishmania major in BALB/c mice. Drug Res (Stuttg). 2015; 65(3):119-124.
24. Firouzmand H, Badiee A, Khamesipour A, et al. Induction of protection against leishmaniasis in susceptible BALB/c mice using simple DOTAP cationic nanoliposomes containing soluble Leishmania antigen (SLA). Acta Trop. 2013; 128(3):528-535.
25. Sen R, Ganguly S, Saha P, et al. Efficacy of artemisinin in experimental visceral leishmaniasis. Int J Antimicrob Agents. 2010; 36(1):43-49.
26. Sen R, Bandyopadhyay S, Dutta A, et al. Artemisinin triggers induction of cell-cycle arrest and apoptosis in Leishmania donovani promastigotes. J Med Microbiol.2007; 56(Pt 9):1213-1218.
27. Tavakoli P, Ghaffarifar F, Delavari H, et al. Efficacy of manganese oxide (Mn2O3) nanoparticles against Leishmania major in vitro and in vivo. J Trace Elem Med Biol. 2019; 56:162-168.
28. Gudovan D, Balaure PC, Eduard Mihaiescu D, et al. Functionalized magnetic nanoparticles for biomedical applications. Curr Pharm Des. 2015; 21(42):6038-6054.
29. Hassan ZM, Feyzi R, Sheikhian A, et al. Low molecular weight fraction of shark cartilage can modulate immune responses and abolish angiogenesis. Int Immunopharmacol. 2005; 5(6):961-970.
30. Wanderley JL, Barcinski MA. Apoptosis and apoptotic mimicry: the Leishmania connection. Cell Mol Life Sci. 2010; 67(10):1653-1659.
31. Zahir AA, Chauhan IS, Bagavan A, et al. Green synthesis of silver and titanium dioxide nanoparticles using Euphorbia prostrata extract shows shift from apoptosis to G0/G1 arrest followed by necrotic cell death in Leishmania donovani. Antimicrob Agents Chemother. 2015; 59(8):4782-4799.
32. Islamuddin M, Chouhan G, Want MY, et al. Corrigendum: Leishmanicidal activities of Artemisia annua leaf essential oil against Visceral Leishmaniasis. Front Microbiol. 2015; 6:1015.
33. de Souza A, Marins DS, Mathias SL, et al. Promising nanotherapy in treating leishmaniasis. Int J Pharm. 2018; 547(1-2):421-431.
34. Kimutai A, Tonui WK, Gicheru MM, et al. Evaluation of the adjuvanticity of artemisinin with soluble Leishmania major antigens in BALB/c mice. J Nanjing Med Univ. 2009; 23(6):359-372.
35. Jebali A, Kazemi B. Nano-based antileishmanial agents: a toxicological study on nanoparticles for future treatment of cutaneous leishmaniasis. Toxicol In vitro. 2013; 27(6):1896-1904.
36. Ebrahimisadr P, Ghaffarifar F, Hassan ZM, et al. Effect of polyvinyl alcohol (PVA) containing artemether in treatment of cutaneous leishmaniasis caused by Leishmania major in BALB/c mice. Jundishapur J Microbiol. 2014; 7(5): e9696.
37. Handman E, Bullen DV. Interaction of Leishmania with the host macrophage Trends Parasitol. 2002; 18(8):332-324.
38. Liu D, Uzonna JE. The early interaction of Leishmania with macrophages and dendritic cells and its influence on the host immune response. Front Cell Infect Microbiol. 2012; 2:83.
39. Lang T, Courret N, Colle JH, et al. The levels and patterns of cytokines produced by CD4 T lymphocytes of BALB/c mice infected with Leishmania major by inoculation into the ear dermis depend on the infectiousness and size of the inoculum. Infect Immun. 2003; 71(5):2674-2683.
40. Owais M, Gupta CM. Targeted drug delivery to macrophages in parasitic infections. Curr Drug Deliv. 2005; 2(4):311-318.
|Issue||Vol 15 No 4 (2020)|
|Artemisinin Glucantime Shark cartilage extract Leishmania major|
|Rights and permissions|
|This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.|