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Protein & Peptide Letters

Author(s): Simone Katz, Clara Lúcia Barbiéri, Fernanda Paula Martins Soler, Andreimar Martins Soares, Maria Cristina Chavantes and Stella Regina Zamuner*

DOI: 10.2174/0929866527666200129152954

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Effect of Isolated Proteins from Crotalus Durissus Terrificus Venom on Leishmania (Leishmania) Amazonensis-Infected Macrophages

Page: [718 - 724] Pages: 7

  • * (Excluding Mailing and Handling)

Abstract

Background: Cutaneous and mucocutaneous leishmaniasis are parasitic diseases characterized by skin manifestations. In Brazil, Leishmania (Leishmania) amazonensis is one of the etiological agents of cutaneous leishmaniasis. The therapeutic arsenal routinely employed to treat infected patients is unsatisfactory, especially for pentavalent antimonials, as they are often highly toxic, poorly tolerated and of variable effectiveness. This study aimed to evaluate in vitro the leishmanicidal activity of toxins isolated from Crotalus durissus terrificus venom as a new approach for the treatment of leishmaniasis.

Methods: The comparative effects of crotamine, crotoxin, gyrotoxin, convulxin and PLA2 on bone marrow-derived macrophages infected with L. (L.) amazonensis as well as the release of TGF-β from the treated macrophages were studied.

Results and Discussion: Crotamine had the strongest inhibitory effect on parasite growth rate (IC50: 25.65±0.52 μg/mL), while convulxin showed the weakest inhibitory effect (IC50: 52.7±2.21 μg/mL). In addition, TGF-β was significantly reduced after the treatment with all toxins evaluated.

Conclusion: The Crotalus durissus terrificus toxins used in this study displayed significant activity against L. (L.) amazonensis, indicating that all of them could be a potential alternative for the treatment of cutaneous leishmaniasis.

Keywords: Crotalus durissus terrificus toxins, parasitic diseases, cutaneous leishmaniasis, Leishmania (Leishmania) amazonensis, macrophages, TGF-β.

Graphical Abstract

[1]
Utzinger, J.; Becker, S.L.; Knopp, S.; Blum, J.; Neumayr, A.L.; Keiser, J.; Hatz, C.F. Neglected tropical diseases: Diagnosis, clinical management, treatment and control. Swiss Med. Wkly., 2012, 142w13727
[http://dx.doi.org/10.4414/smw.2012.13727] [PMID: 23180107]
[2]
Burza, S.; Croft, S.L.; Boelaert, M. Leishmaniasis. Lancet, 2018, 392(10151), 951-970.
[http://dx.doi.org/10.1016/S0140-6736(18)31204-2] [PMID: 30126638]
[3]
Silveira, F.T.; Lainson, R.; Corbett, C.E.P. Clinical and immunopathological spectrum of American cutaneous leishmaniasis with special reference to the disease in Amazonian Brazil: A review. Mem. Inst. Oswaldo Cruz, 2004, 99(3), 239-251.
[http://dx.doi.org/10.1590/S0074-02762004000300001] [PMID: 15273794]
[4]
Bahrami, F.; Harandi, A.M.; Rafati, S. Biomarkers of cutaneous leishmaniasis. Front. Cell. Infect. Microbiol., 2018, 26(8), 2235-2988.
[http://dx.doi.org/10.3389/fcimb.2018.00222]
[5]
den Boer, M.; Argaw, D.; Jannin, J.; Alvar, J. Leishmaniasis impact and treatment access. Clin. Microbiol. Infect., 2011, 17(10), 1471-1477.
[http://dx.doi.org/10.1111/j.1469-0691.2011.03635.x] [PMID: 21933305]
[6]
Barbosa, A.F.; Sangiorgi, B.B.; Galdino, S.L.; Barral-Netto, M.; Pitta, I.R.; Pinheiro, A.L. Photodynamic Antimicrobial Chemotherapy (PACT) using phenothiazine derivatives as photosensitizers against Leishmania braziliensis. Lasers Surg. Med., 2012, 44(10), 850-855.
[http://dx.doi.org/10.1002/lsm.22099] [PMID: 23184450]
[7]
Haldar, A.K.; Banerjee, S.; Naskar, K.; Kalita, D.; Islam, N.S.; Roy, S. Sub-optimal dose of Sodium Antimony Gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania donovani by expanding antileishmanial T-cell repertoire and increasing IFN-gamma to IL-10 ratio. Exp. Parasitol., 2009, 122(2), 145-154.
[http://dx.doi.org/10.1016/j.exppara.2009.02.001] [PMID: 19422069]
[8]
Marcussi, S.; Santos, P.R.; Menaldo, D.L.; Silveira, L.B.; Santos-Filho, N.A.; Mazzi, M.V.; da Silva, S.L.; Stábeli, R.G.; Antunes, L.M.; Soares, A.M. Evaluation of the genotoxicity of Crotalus durissus terrificus snake venom and its isolated toxins on human lymphocytes. Mutat. Res., 2011, 724(1-2), 59-63.
[http://dx.doi.org/10.1016/j.mrgentox.2011.06.004] [PMID: 21723956]
[9]
Yonamine, C.M.; Kondo, M.Y.; Juliano, M.A.; Icimoto, M.Y.; Baptista, G.R.; Yamane, T.; Oliveira, V.; Juliano, L.; Lapa, A.J.; Lima-Landman, M.T.; Hayashi, M.A. Kinetic characterization of gyroxin, a serine protease from Crotalus durissus terrificus venom. Biochimie, 2012, 94(12), 2791-2793.
[http://dx.doi.org/10.1016/j.biochi.2012.07.020] [PMID: 22898589]
[10]
Batista da Cunha, D.; Pupo Silvestrini, A.V.; Gomes da Silva, A.C.; Maria de Paula Estevam, D.; Pollettini, F.L.; de Oliveira Navarro, J.; Alves, A.A.; Remédio Zeni Beretta, A.L.; Annichino Bizzacchi, J.M.; Pereira, L.C.; Mazzi, M.V. Mechanistic insights into functional characteristics of native crotamine. Toxicon, 2018, 146, 1-12.
[http://dx.doi.org/10.1016/j.toxicon.2018.03.007] [PMID: 29574214]
[11]
Oguiura, N.; Boni-Mitake, M.; Affonso, R.; Zhang, G. In vitro antibacterial and hemolytic activities of crotamine, a small basic myotoxin from rattlesnake Crotalus durissus. J. Antibiot. (Tokyo), 2011, 64(4), 327-331.
[http://dx.doi.org/10.1038/ja.2011.10] [PMID: 21386851]
[12]
Rübsamen, K.; Breithaupt, H.; Habermann, E. Biochemistry and pharmacology of the crotoxin complex. I. Subfractionation and recombination of the crotoxin complex. Naunyn Schmiedebergs Arch. Pharmakol., 1971, 270(3), 274-288.
[http://dx.doi.org/10.1007/BF00997027] [PMID: 4254625]
[13]
Kanaji, S.; Kanaji, T.; Furihata, K.; Kato, K.; Ware, J.L.; Kunicki, T.J. Convulxin binds to native, human glycoprotein Ib alpha. J. Biol. Chem., 2003, 278(41), 39452-39460.
[http://dx.doi.org/10.1074/jbc.M300199200] [PMID: 12881531]
[14]
Tempone, A.G.; Andrade, H.F. Jr.; Spencer, P.J.; Lourenço, C.O.; Rogero, J.R.; Nascimento, N. Bothrops moojeni venom kills Leishmania spp. with hydrogen peroxide generated by its L-amino acid oxidase. Biochem. Biophys. Res. Commun., 2001, 280(3), 620-624.
[http://dx.doi.org/10.1006/bbrc.2000.4175] [PMID: 11162565]
[15]
Fernandez-Gomez, R.; Zerrouk, H.; Sebti, F.; Loyens, M.; Benslimane, A.; Ouaissi, M.A. Growth inhibition of Trypanosoma cruzi and Leishmania donovani infantum by different snake venoms: Preliminary identification of proteins from Cerastes cerastes venom which interact with the parasites. Toxicon, 1994, 32(8), 875-882.
[http://dx.doi.org/10.1016/0041-0101(94)90366-2] [PMID: 7985193]
[16]
Peichoto, M.E.; Tavares, F.L.; Dekrey, G.; Mackessy, S.P. A comparative study of the effects of venoms from five rear-fanged snake species on the growth of Leishmania major: Identification of a protein with inhibitory activity against the parasite. Toxicon, 2011, 58(1), 28-34.
[http://dx.doi.org/10.1016/j.toxicon.2011.04.018] [PMID: 21601589]
[17]
Bhattacharya, S.; Ghosh, P.; De, T.; Gomes, A.; Gomes, A.; Dungdung, S.R. In vivo and in vitro antileishmanial activity of Bungarus caeruleus snake venom through alteration of immunomodulatory activity. Exp. Parasitol., 2013, 135(1), 126-133.
[http://dx.doi.org/10.1016/j.exppara.2013.06.006] [PMID: 23830987]
[18]
Passero, L.F.D.; Tomokane, T.Y.; Corbett, C.E.P.; Laurenti, M.D.; Toyama, M.H. Comparative studies of the anti-leishmanial activity of three Crotalus durissus ssp. venoms. Parasitol. Res., 2007, 101(5), 1365-1371.
[http://dx.doi.org/10.1007/s00436-007-0653-1] [PMID: 17659386]
[19]
Farias, L.H.S.; Rodrigues, A.P.D.; Coêlho, E.C.; Santos, M.F.; Sampaio, S.C.; Silva, E.O. Crotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection. Parasitology, 2017, 144(11), 1458-1467.
[http://dx.doi.org/10.1017/S0031182017000944] [PMID: 28641584]
[20]
Barros, G.A.; Pereira, A.V.; Barros, L.C.; Lourenço, A., Jr; Calvi, S.A.; Santos, L.D.; Barraviera, B.; Ferreira, R.S. Jr. In vitro activity of phospholipase A2 and of peptides from Crotalus durissus terrificus venom against amastigote and promastigote forms of Leishmania (L.) infantum chagasi. J. Venom. Anim. Toxins Incl. Trop. Dis., 2015, 21, 48.
[http://dx.doi.org/10.1186/s40409-015-0049-0] [PMID: 26609302]
[21]
Barbiéri, C.L.; Doine, A.I.; Freymuller, E. Lysosomal depletion in macrophages from spleen and foot lesions of Leishmania-infected hamster. Exp. Parasitol., 1990, 71(2), 218-228.
[http://dx.doi.org/10.1016/0014-4894(90)90024-7] [PMID: 2373189]
[22]
Zamboni, D.S.; Rabinovitch, M. Nitric oxide partially controls Coxiella burnetii phase II infection in mouse primary macrophages. Infect. Immun., 2003, 71(3), 1225-1233.
[http://dx.doi.org/10.1128/IAI.71.3.1225-1233.2003] [PMID: 12595436]
[23]
Paladi, Cde. S.; Pimentel, I.A.S.; Katz, S.; Cunha, R.L.O.R.; Judice, W.A.S.; Caires, A.C.F.; Barbiéri, C.L. In vitro and in vivo activity of a palladacycle complex on Leishmania (Leishmania) amazonensis. PLoS Negl. Trop. Dis., 2012, 6(5), e1626.
[http://dx.doi.org/10.1371/journal.pntd.0001626] [PMID: 22616018]
[24]
Adade, C.M.; Carvalho, A.L.O.; Tomaz, M.A.; Costa, T.F.R.; Godinho, J.L.; Melo, P.A.; Lima, A.P.C.A.; Rodrigues, J.C.F.; Zingali, R.B.; Souto-Padrón, T. Crovirin, a snake venom cysteine-rich secretory protein (CRISP) with promising activity against Trypanosomes and Leishmania. PLoS Negl. Trop. Dis., 2014, 8(10)e3252
[http://dx.doi.org/10.1371/journal.pntd.0003252] [PMID: 25330220]
[25]
Passero, L.F.; Laurenti, M.D.; Tomokane, T.Y.; Corbett, C.E.; Toyama, M.H. The effect of phospholipase A2 from Crotalus durissus collilineatus on Leishmania (Leishmania) amazonensis infection. Parasitol. Res., 2008, 102(5), 1025-1033.
[http://dx.doi.org/10.1007/s00436-007-0871-6] [PMID: 18180953]
[26]
Gonçalves, A.R.; Soares, M.J.; de Souza, W.; DaMatta, R.A.; Alves, E.W. Ultrastructural alterations and growth inhibition of Trypanosoma cruzi and Leishmania major induced by Bothrops jararaca venom. Parasitol. Res., 2002, 88(7), 598-602.
[http://dx.doi.org/10.1007/s00436-002-0626-3] [PMID: 12107450]
[27]
Costa-Torres, A.F.; Dantas, R.T.; Toyama, M.H.; Diz Filho, E.; Zara, F.J.; Rodrigues de Queiroz, M.G.; Pinto-Nogueira, N.A.; Rosa de Oliveira, M.; de Oliveira Toyama, D.; Monteiro, H.S.; Martins, A.M. Antibacterial and antiparasitic effects of Bothrops marajoensis venom and its fractions: Phospholipase A2 and L-amino acid oxidase. Toxicon, 2010, 55(4), 795-804.
[http://dx.doi.org/10.1016/j.toxicon.2009.11.013] [PMID: 19944711]
[28]
Toyama, M.H. Toyama, Dde.O.; Passero, L.F.; Laurenti, M.D.; Corbett, C.E.; Tomokane, T.Y.; Fonseca, F.V.; Antunes, E.; Joazeiro, P.P.; Beriam, L.O.; Martins, M.A.; Monteiro, H.S.; Fonteles, M.C. Isolation of a new L-amino acid oxidase from Crotalus durissus cascavella venom. Toxicon, 2006, 47(1), 47-57.
[http://dx.doi.org/10.1016/j.toxicon.2005.09.008] [PMID: 16307769]
[29]
Dos Santos, I.B.; da Silva, D.A.M.; Paz, F.A.C.R.; Garcia, D.M.; Carmona, A.K.; Teixeira, D.; Longo-Maugéri, I.M.; Katz, S.; Barbiéri, C.L. Leishmanicidal and immunomodulatory activities of the Palladacycle Complex DPPE 1.1, a Potential candidate for treatment of cutaneous Leishmaniasis. Front. Microbiol., 2018, 9, 1427.
[http://dx.doi.org/10.3389/fmicb.2018.01427] [PMID: 30018604]
[30]
Abdoli, A.; Maspi, N.; Ghaffarifar, F. Wound healing in cutaneous leishmaniasis: A double edged sword of IL-10 and TGF-β. Comp. Immunol. Microbiol. Infect. Dis., 2017, 51, 15-26.
[http://dx.doi.org/10.1016/j.cimid.2017.02.001] [PMID: 28504090]
[31]
Barral-Netto, M.; Barral, A.; Brownell, C.E.; Skeiky, Y.A.; Ellingsworth, L.R.; Twardzik, D.R.; Reed, S.G. Transforming growth factor-beta in leishmanial infection: A parasite escape mechanism. Science, 1992, 257(5069), 545-548.
[http://dx.doi.org/10.1126/science.1636092] [PMID: 1636092]