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Infectious Disorders - Drug Targets

Author(s): Negar Asadi, Elham Yousefi*, Khosrow Hazrati Tappeh and Shahram Khademvatan*

DOI: 10.2174/1871526522666220117120303

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Anti-toxoplasma and Cytotoxic Activities of Holothuria leucospilota Extract and TiO2NPs In vitro and In vivo

Article ID: e170122200295 Pages: 8

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Abstract

Background: An impressive treatment for toxoplasmosis is the combinatory use of sulfadiazine and pyrimethamine. However, both the drugs involve significant side effects and toxicity for the host. Therefore, the discovery of new anti-toxoplasma medications with high efficacy and less to no side effects is urgently needed.

Objective: This study aimed to evaluate the anti-toxoplasmic effects of Holothuria leucospilota (H. leucospilota) extract and TiO2NPs on the cell death of Toxoplasma gondii (T. gondii) tachyzoites in vitro and serum liver enzymes (AST, ALT, and ALP), and also to evaluate the immune response and production of IL-5, IFN-γ, and TNF-α in a mouse model.

Materials and Methods: The cytotoxicity of TiO2NPs and H. leucospilota extract against the tachyzoite of T. gondii was evaluated by the methyl thiazolyl tetrazolium (MTT) assay. The levels of serum TNF-α, IFN-γ, IL-5, and liver enzymes were measured, as well. All the groups were subjected to T. gondii, and the survival rate of experimental mice was evaluated.

Results: Our findings suggested in vivo and in vitro anti-toxoplasmic activity of TiO2NPs and H. leucospilota extract by inhibiting the proliferation and invasion of T. gondii tachyzoite. In addition, a significant increase in IFN-γ and TNF-α production was observed in mice treated with high doses of TiO2NPs and H. leucospilota extract. However, IL-5 levels decreased in TiO2NPs and H. leucospilota extract-treated mice. Our results also showed a highly significant increase (P < 0.05) in the levels of ALT, AST, and ALP in the groups injected with TiO2NPs and H. leucospilota extract, but not the control group.

Conclusion: TiO2NPs and H. leucospilota extract have greater anti-toxoplasma effects in vitro and in vivo. These two compounds could be considered as a candidate for use against toxoplasmosis, both therapeutically and prophylactically.

Keywords: Toxoplasma gondii, H. leucospilota, titanium dioxide, BALB/c, immunomodulatory, nanoparticles, liver enzymes.

Graphical Abstract

[1]
Frenkel JK. Pathophysiology of toxoplasmosis. Parasitol Today 1988; 4(10): 273-8.
[http://dx.doi.org/10.1016/0169-4758(88)90018-X] [PMID: 15463000]
[2]
Cook AJ, Gilbert RE, Buffolano W, et al. Sources of toxoplasma infection in pregnant women: European multicentre case-control study. BMJ 2000; 321(7254): 142-7.
[http://dx.doi.org/10.1136/bmj.321.7254.142] [PMID: 10894691]
[3]
Khademvatan S, Khademvatani K, Tappeh KH, Asadi N, Khezri P, Abasi E. Association of toxoplasma gondii infection with cardiovascular diseases: A cross-sectional study among patients with heart failure diseases in Urmia, North-West of Iran. Ann Parasitol 2020; 66(2): 193-9.
[http://dx.doi.org/10.17420/ap6602.254] [PMID: 32592458]
[4]
Saki J, Mohammadpour N, Moramezi F, Khademvatan S. Seroprevalence of toxoplasma gondii in women who have aborted in comparison with the women with normal delivery in Ahvaz, Southwest of Iran. Sci World J 2015; 2015: 764369.
[http://dx.doi.org/10.1155/2015/764369] [PMID: 25699288]
[5]
Khademvatan S, Foroutan M, Hazrati-Tappeh K, et al. Toxoplasmosis in rodents: A systematic review and meta-analysis in Iran. J Infect Public Health 2017; 10(5): 487-93.
[http://dx.doi.org/10.1016/j.jiph.2017.01.021] [PMID: 28237696]
[6]
Porter SB, Sande MA. Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome. N Engl J Med 1992; 327(23): 1643-8.
[http://dx.doi.org/10.1056/NEJM199212033272306] [PMID: 1359410]
[7]
Weiss LM, Dubey JP. Toxoplasmosis: A history of clinical observations. Int J Parasitol 2009; 39(8): 895-901.
[http://dx.doi.org/10.1016/j.ijpara.2009.02.004] [PMID: 19217908]
[8]
Nissapatorn V. Toxoplasmosis in HIV/AIDS: A living legacy. Southeast Asian J Trop Med Public Health 2009; 40(6): 1158-78.
[PMID: 20578449]
[9]
Bosch-Driessen LH, Verbraak FD, Suttorp-Schulten MS, et al. A prospective, randomized trial of pyrimethamine and azithromycin vs pyrimethamine and sulfadiazine for the treatment of ocular toxoplasmosis. Am J Ophthalmol 2002; 134(1): 34-40.
[http://dx.doi.org/10.1016/S0002-9394(02)01537-4] [PMID: 12095805]
[10]
Hampton MM. Congenital toxoplasmosis: A review. Neonatal Netw 2015; 34: 274-8.
[http://dx.doi.org/10.1891/0730-0832.34.5.274] [PMID: 26802827]
[11]
Si K, Wei L, Yu X, et al. Effects of (+)-usnic acid and (+)-usnic acid-liposome on Toxoplasma gondii. Exp Parasitol 2016; 166: 68-74.
[http://dx.doi.org/10.1016/j.exppara.2016.03.021] [PMID: 27004468]
[12]
Mordue DG, Monroy F, La Regina M, Dinarello CA, Sibley LD. Acute toxoplasmosis leads to lethal overproduction of Th1 cytokines. J Immunol 2001; 167(8): 4574-84.
[http://dx.doi.org/10.4049/jimmunol.167.8.4574] [PMID: 11591786]
[13]
Ustun S, Aksoy U, Dagci H, Ersoz G. Incidence of toxoplasmosis in patients with cirrhosis. World J Gastroenterol 2004; 10(3): 452-4.
[http://dx.doi.org/10.3748/wjg.v10.i3.452] [PMID: 14760779]
[14]
He J-J, Ma J, Elsheikha HM, Song H-Q, Zhou D-H, Zhu X-Q. Proteomic profiling of mouse liver following acute Toxoplasma gondii infection. PLoS One 2016; 11(3): e0152022.
[http://dx.doi.org/10.1371/journal.pone.0152022] [PMID: 27003162]
[15]
He J-J, Ma J, Elsheikha HM, Song H-Q, Huang S-Y, Zhu X-Q. Transcriptomic analysis of mouse liver reveals a potential hepato-enteric pathogenic mechanism in acute Toxoplasma gondii infection. Parasit Vectors 2016; 9(1): 427.
[http://dx.doi.org/10.1186/s13071-016-1716-x] [PMID: 27488578]
[16]
Jaeschke H. Reactive oxygen and mechanisms of inflammatory liver injury. J Gastroenterol Hepatol 2000; 15(7): 718-24.
[http://dx.doi.org/10.1046/j.1440-1746.2000.02207.x] [PMID: 10937675]
[17]
Das S, Bhattacharya A, Debnath N, Datta A, Goswami A. Nanoparticle-induced morphological transition of Bombyx mori nucleopolyhedrovirus: a novel method to treat silkworm grasserie disease. Appl Microbiol Biotechnol 2013; 97(13): 6019-30.
[http://dx.doi.org/10.1007/s00253-013-4868-z] [PMID: 23588933]
[18]
Anthony J-P, Fyfe L, Smith H. Plant active components - a resource for antiparasitic agents? Trends Parasitol 2005; 21(10): 462-8.
[http://dx.doi.org/10.1016/j.pt.2005.08.004] [PMID: 16099722]
[19]
Haider M, Sultana R, Jamil K, Tarar O, Afzal W. A study on proximate composition, amino acid profile, fatty acid profile and some mineral contents in two species of sea cucumber. JAPS. J Anim Plant Sci 2015; 25(1): 168-75.
[20]
Mamelona J, Pelletier E, Girard-Lalancette K, Legault J, Karboune S, Kermasha S. Quantification of phenolic contents and antioxidant capacity of Atlantic sea cucumber, Cucumaria frondosa. Food Chem 2007; 104(3): 1040-7.
[http://dx.doi.org/10.1016/j.foodchem.2007.01.016]
[21]
Liu X, Sun Z, Zhang M, et al. Antioxidant and antihyperlipidemic activities of polysaccharides from sea cucumber Apostichopus japonicus. Carbohydr Polym 2012; 90(4): 1664-70.
[http://dx.doi.org/10.1016/j.carbpol.2012.07.047] [PMID: 22944431]
[22]
Hu X-Q, Xu J, Xue Y, et al. Effects of bioactive components of sea cucumber on the serum, liver lipid profile and lipid absorption. Biosci Biotechnol Biochem 2012; 76(12): 2214-8.
[http://dx.doi.org/10.1271/bbb.120495] [PMID: 23221720]
[23]
Foroutan-Rad M, Khademvatan S, Saki J, Hashemitabar M. Holothuria leucospilota extract induces apoptosis in Leishmania major promastigotes. Iran J Parasitol 2016; 11(3): 339-49.
[PMID: 28127339]
[24]
Aryamand S, Khademvatan S, Hazrati Tappeh K, Heshmatian B, Jelodar A. In vitro and in vivo scolicidal activities of Holothuria leucospilota extract and CeO2 nanoparticles against hydatid Cyst. Iran J Parasitol 2019; 14(2): 269-79.
[PMID: 31543915]
[25]
Esmat AY, Said MM, Soliman AA, El-Masry KS, Badiea EA. Bioactive compounds, antioxidant potential, and hepatoprotective activity of sea cucumber (Holothuria atra) against thioacetamide intoxication in rats. Nutrition 2013; 29(1): 258-67.
[http://dx.doi.org/10.1016/j.nut.2012.06.004] [PMID: 23085016]
[26]
El-Khadragy M, Alolayan EM, Metwally DM, et al. Clinical efficacy associated with enhanced antioxidant enzyme activities of silver nanoparticles biosynthesized using Moringa oleifera leaf extract, against cutaneous leishmaniasis in a murine model of Leishmania major. Int J Environ Res Public Health 2018; 15(5): 1037.
[http://dx.doi.org/10.3390/ijerph15051037] [PMID: 29786651]
[27]
Ling D, Lee N, Hyeon T. Chemical synthesis and assembly of uniformly sized iron oxide nanoparticles for medical applications. Acc Chem Res 2015; 48(5): 1276-85.
[http://dx.doi.org/10.1021/acs.accounts.5b00038] [PMID: 25922976]
[28]
Schanen BC, Das S, Reilly CM, et al. Immunomodulation and T helper TH1/TH2 response polarization by CeO2 and TiO2 nanoparticles. PLoS One 2013; 8(5): e62816.
[http://dx.doi.org/10.1371/journal.pone.0062816] [PMID: 23667525]
[29]
Asadi N, Khademvatan S, Mohammadzadeh H, Heshmatiyan B, Asghari S, Foroutan M. The cytotoxic and immunomodulatory effects of titanium dioxide nanoparticles and Sargassum oligocystum on Toxoplasma gondii in vitro and in vivo. Antiinfect Agents 2021; 19(3)
[30]
Allahverdiyev AM, Abamor ES, Bagirova M, Rafailovich M. Antimicrobial effects of TiO2 and Ag2O nanoparticles against drug-resistant bacteria and Leishmania parasites. Future Microbiol 2011; 6(8): 933-40.
[http://dx.doi.org/10.2217/fmb.11.78] [PMID: 21861623]
[31]
Karamkhani A, Saki J. Assessment of apoptosis induction by methanol extract of sea cucumber in Blastocystis hominis isolated from human samples using flow cytometry and DNA fragmentation test. Jundishapur J Nat Pharm Prod 2019; 14(2): e13959.
[http://dx.doi.org/10.5812/jjnpp.13959]
[32]
Adibpour N, Nasr F, Nematpour F, Shakouri A, Ameri A. Antibacterial and antifungal activity of Holothuria leucospilota isolated from Persian Gulf and Oman sea. Jundishapur J Microbiol 2014; 7(1): e8708.
[http://dx.doi.org/10.5812/jjm.8708] [PMID: 25147657]
[33]
Dhinakaran DI, Lipton A. Pharmacological potentials of sea cucumber Holothuria atra extracts from the Indian Ocean. Asian J Biomed Pharm Sci 2014; 4(35): 36-43.
[http://dx.doi.org/10.15272/ajbps.v4i35.537]
[34]
Althunibat OY, Ridzwan BH, Taher M, Daud JM, Jauhari Arief Ichwan S, Qaralleh H. Antioxidant and cytotoxic properties of two sea cucumbers, Holothuria edulis lesson and Stichopus horrens selenka. Acta Biol Hung 2013; 64(1): 10-20.
[http://dx.doi.org/10.1556/ABiol.64.2013.1.2] [PMID: 23567827]
[35]
Foroutan M, Ghaffarifar F, Sharifi Z, Dalimi A, Jorjani O. Rhoptry antigens as Toxoplasma gondii vaccine target. Clin Exp Vaccine Res 2019; 8(1): 4-26.
[http://dx.doi.org/10.7774/cevr.2019.8.1.4] [PMID: 30775347]
[36]
Duan Y, Liu J, Ma L, et al. Toxicological characteristics of nanoparticulate anatase titanium dioxide in mice. Biomaterials 2010; 31(5): 894-9.
[http://dx.doi.org/10.1016/j.biomaterials.2009.10.003] [PMID: 19857890]
[37]
Cui Y, Liu H, Ze Y, et al. Gene expression in liver injury caused by long-term exposure to titanium dioxide nanoparticles in mice. Toxicol Sci 2012; 128(1): 171-85.
[http://dx.doi.org/10.1093/toxsci/kfs153] [PMID: 22539623]
[38]
Cui Y, Gong X, Duan Y, et al. Hepatocyte apoptosis and its molecular mechanisms in mice caused by titanium dioxide nanoparticles. J Hazard Mater 2010; 183(1-3): 874-80.
[http://dx.doi.org/10.1016/j.jhazmat.2010.07.109] [PMID: 20724067]