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A Novel Organotellurium Compound (RT-01) as a New Antileishmanial Agent

  • Published : 2009.09.30

Abstract

Leishmaniasis is a neglected disease and endemic in developing countries. A lack of adequate and definitive chemotherapeutic agents to fight against this infection has led to the investigation of numerous compounds. The aim of this study was to investigate the effect of RT-01, an organotellurane compound presenting biological activities, in 2 experimental systems against Leishmania amazonensis. The in vitro system consisted of promastigotes and amastigotes forms of the parasite, and the in vivo system consisted of L.amazonensis infected BALB/c mice, an extremely susceptible mouse strain. The compound proved to be toxic against promastigotes and amastigotes. The study also showed that treatment with RT-01 produces an effect similar to that treatment with the reference antimonial drug, Glucantime, in L.amazonensis infected mice. The best results were obtained following RT-01 intralesional administration (720 ${\mu}g$/kg/day); mice showed significant delay in the development of cutaneous lesions and decreased numbers of parasites obtained from the lesions. Significant differences in tissue pathology consisted mainly of no expressive accumulation of inflammatory cells and wellpreserved structures in the skin tissue of RT-01-treated mice compared with expressive infiltration of infected cells replacing the skin tissue in lesions of untreated mice. These findings highlight the fact that the apparent potency of organotellurane compounds, together with their relatively simple structure, may represent a new avenue for the development of novel drugs to combat parasitic diseases.

Keywords

References

  1. Murray HW, Berman JD, Davies CR, Saravia NG. Advances in leishmaniasis. Lancet 2005; 366: 1561-1577 https://doi.org/10.1016/S0140-6736(05)67629-5
  2. Grimaldi GJ, Tesh RB. Leishmaniasis of the new world: current concepts and implications for future research. Clin Microbiol Rev 1993; 6: 230-250 https://doi.org/10.1128/CMR.6.3.230
  3. Desjeux P. Leishmaniasis: current situation and new perspectives. Comp Immunol Microbiol Infect Dis 2004; 27: 305-318 https://doi.org/10.1016/j.cimid.2004.03.004
  4. Mishra, JA, Saxena A, Singh S. Chemotherapy of leishmaniasis: past, present and future. Cur Med Chem 2007; 14: 1153-1169 https://doi.org/10.2174/092986707780362862
  5. Nogueira CW, Zeni G, Rocha JBT. Organoselenium and organotellurium compounds: toxicology and pharmacology. Chem Rev 2004; 104: 6255-6285 https://doi.org/10.1021/cr0406559
  6. Chasteen TG, Bentley R. Biomethylation of selenium and tellurium: microorganisms and plants. Chem Rev 2003; 103: 1-25 https://doi.org/10.1021/cr010210+
  7. Cunha RL, Urano ME, Chagas JR, Almeida PC, Bincoletto C, Tersariol IL, Comasseto JV. Tellurium-based cysteine protease inhibitors: evaluation of novel organotellurium (IV) compounds as inhibitors of human cathepsin B. Bioorg Med Chem Lett 2005; 15: 755-760 https://doi.org/10.1016/j.bmcl.2004.11.012
  8. Abondanza TS, Oliveira CR, Barbosa CM, Pereira FE, Cunha RL, Caires AC, Comasseto JV, Queiroz ML, Valadares MC, Bincoletto C. Bcl-2 expression and apoptosis induction in human HL60 leukaemic cells treated with a novel organotellurium (IV) compound RT-04. Food Chem Toxicol 2008; 46: 2540-2545 https://doi.org/10.1016/j.fct.2008.04.010
  9. Sredni B, Caspi RR, Klein A, Kalechman Y, Danziger Y, Ben Ya'akov M, Tamari T, Shalit F, Albeck M. A new immunomodulating compound (AS-101) with potential therapeutic application. Nature 1987; 330: 173-176 https://doi.org/10.1038/330173a0
  10. Wieslander E, Engman L, Svensjo E, Erlansson M, Johansson U, Linden M, Andersson CM, Brattsand R. Antioxidative properties of organotellurium compounds in cell systems. Biochem Pharmacol 1998; 55: 573-584 https://doi.org/10.1016/S0006-2952(97)00517-0
  11. Garberg P, Engman L, Tolmachev V, Lundqvist H, Gerdes RG, Cotgreave IA. Binding of tellurium to hepatocellular selenoproteins during incubation with inorganic tellurite: consequences for the activity of selenium-dependent glutathione peroxidase. Int J Biochem Cell Biol 1999; 31: 291-301 https://doi.org/10.1016/S1357-2725(98)00113-7
  12. Sailer BL, Liles N, Dickerson S, Chasteen TG. Cytometric determination of novel organotellurium compound toxicity in a promyelocytic (HL-60) cell line. Arch Toxicol 2003; 77: 30-36 https://doi.org/10.1007/s00204-002-0407-x
  13. Sredni B, Xu RH, Albeck M, Gafter U, Gal R, Shani A, Tichler T, Shapira J, Bruderman I, Catane R, Kaufman B, Whisnant JK, Mettinger KL, Kalechman Y. The protective role of the immunomodulator AS101 against chemotherapy-induced alopecia: studies on human and animal models. Int J Cancer 1996; 65: 97-103 https://doi.org/10.1002/(SICI)1097-0215(19960103)65:1<97::AID-IJC17>3.0.CO;2-F
  14. Sredni-Kenigsbuch D, Shohat M, Shohat B, Ben-Amitai D, Chan CC, David M. The novel tellurium immunomodulator AS101 inhibits interleukin-10 production and p38 MAPK expression in atopic dermatitis. J Dermatol Sci 2008; 50: 232-235 https://doi.org/10.1016/j.jdermsci.2007.12.007
  15. Zukerman-Schpector J, Camillo RL, Comasseto JV, Cunha RLOR,Caracelli I. Benzyltriethylammonium 2,2,2,4-tetrachloro-2,5-dihy-dro-1,2${\lambda}^{5}$-oxatellurole. Acta Cryst 2000; C56: 897-898 https://doi.org/10.1107/S0108270100005515
  16. Barbieri CL, Giorgio S, Merjan AJ, Figueiredo EM. Glycosphingolipid antigens from Leishmania (Leishmania) amazonensis amastigotes identified by use of a monoclonal antibody. Infect Immun 1993: 61: 2132-2137
  17. Arrais-Silva WW, Collhone MC, Ayres DC, de Souza Souto PC, Giorgio S. Effects of hyperbaric oxygen on Leishmania amazonensis promastigotes and amastigotes. Parasitol Int 2005; 54: 1-7 https://doi.org/10.1016/j.parint.2004.07.002
  18. Linares E, Giorgio S, Mortara RA, Santos CX, Yamada AT, Augusto O. Role of peroxynitrite in macrophage microbicidal mechanisms in vivo revealed by protein nitration and hydroxylation. Free Rad Biol Med 2001; 30: 1234-1242 https://doi.org/10.1016/S0891-5849(01)00516-0
  19. Lemestre JP, Sereno D, Daulouede S, Veyret B, Brajon N, Vincendeau P. Leishmania spp.: nitric oxide-mediated metabolic inhibition of promastigote and axenically growth amastigote form. Exp Parasitol 1997; 86: 58-68 https://doi.org/10.1006/expr.1997.4151
  20. Arrais-Silva WW, Pinto EF, Rossi-Bergmann B, Giorgio S. Hyperbaric oxygen therapy reduces the size of Leishmania amazonensisinduced soft tissue lesions in mice. Acta Trop 2006; 98: 130-136 https://doi.org/10.1016/j.actatropica.2006.03.001
  21. Rosenblatt-Bin H, Klein A, Sredni B. Antibabesial effect of the immunomodulator AS101 in mice: role of increased production of nitric oxide. Parasite Immunol 1996; 18: 297-306 https://doi.org/10.1046/j.1365-3024.1996.d01-104.x
  22. Matlashewski G. Leishmania infection and virulence. Med Microbiol Immunol 2001; 190: 37-42 https://doi.org/10.1007/s004300100076
  23. Mottram JC, Souza AE, Hutchison JE, Carter R, Frame MJ, Coombs GH. Evidence from disruption of the lmcpb gene array of Leishmania mexicana that cysteine proteinases are virulence factors. Proc Natl Acad Sci USA 1996; 93: 6008-6013 https://doi.org/10.1073/pnas.93.12.6008
  24. Barral-Netto M, Cardoso SA, Barral A. Different patterns of disease in two inbred mouse strains infected with a clone of Leishmania mexicana amazonensis. Acta Trop 1987; 44: 5-11
  25. Macharia JC, Bourdichon AJ, Gicheru MM. Efficacy of Trypan: a diminazene based drug as antileishmanial agent. Acta Trop 2004; 92: 267-272 https://doi.org/10.1016/j.actatropica.2004.08.008
  26. Frei GM, Kremer M, Hanschmann KM, Krause S, Albeck M, Sredni B, Schnierle BS. Antitumour effects in mycosis fungoides of the immunomodulatory, tellurium-based compound, AS101. Br J Dermatol 2008; 158: 578-586 https://doi.org/10.1111/j.1365-2133.2007.08414.x
  27. Hayun R, Shpungin S, Malovani H, Albeck M, Okun E, Nir U, Sredni B. Novel involvement of the immunomodulator AS101 in IL-10 signaling, via the tyrosine kinase Fer. Ann N Y Acad Sci 2007; 1095: 240-250 https://doi.org/10.1196/annals.1397.028
  28. Kalechman Y, Gafter U, Da JP, Albeck M, Alarcon-Segovia D, Sredni B. Delay in the onset of systemic lupus erythematosus following treatment with the immunomodulator AS101: association with IL-10 inhibition and increase in TNF-alpha levels. J Immunol 1997; 159: 2658-2667
  29. Sredni B, Kalechman Y, Albeck M, Gross O, Aurbach D, Sharon P, Sehgal SN, Gurwith MJ, Michlin H. Cytokine secretion effected by synergism of the immunomodulator AS101 and the protein kinase C inducer bryostatin. Immunology 1990; 70: 473-477
  30. Shohat M, Hodak E, Sredni B, Shohat B, Sredni D, David M. Cytokine profile of patients with mycosis fungoides and the immunomodulatory effect of AS101. Acta Derm Venereol 2001; 81: 255-257 https://doi.org/10.1080/00015550152572877

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