MARBOFLOXACIN INDUCES LEISHMANICIDAL ACTIVITY AND LESS INFLAMMATORY RESPONSE IN Leishmania chagasi INFECTED MACROPHAGES

Authors

  • João Francisco dos Anjos Alvarenga Amante Sao Paulo State University (UNESP), Botucatu, Brazil
  • Amanda Ribeiro Santos Sao Paulo State University (UNESP), Bauru, Brazil
  • Bárbara Mello Santos Sao Paulo State University (UNESP), Bauru, Brazil
  • Karine Bott Mantovan Universidade Estadual "Julio de Mesquita Filho"
  • Sâmea Fernandes Joaquim Sao Paulo State University (UNESP), Botucatu, Brazil
  • Giulia Soares Latosinski Sao Paulo State University (UNESP), Botucatu, Brazil https://orcid.org/0000-0001-5390-5610
  • Benedito Donizete Menozzi Sao Paulo State University (UNESP), Botucatu, Brazil
  • Alexandre Hataka Sao Paulo State University (UNESP), Botucatu, Brazil
  • Simone Baldini Lucheis Sao Paulo State University (UNESP), Botucatu, Brazil
  • James Venturini Federal University of Mato Grosso do Sul, UFMS, Brazil
  • Helio Langoni Sao Paulo State University (UNESP), Botucatu, Brazil

DOI:

https://doi.org/10.35172/rvz.2020.v27.510

Keywords:

Leishmania chagasi, marbofloxacin, infected macrophages

Abstract

Marbofloxacin has promising leishmanicidal activity due to the direct action on the Leishmania chagasi amastigotes. It was developed only for veterinary medicine uses, and it could be used as an drug for the treatment of Canine Visceral Leishmaniasis (CVL). In the present study, we evaluated the leishmanicidal effect and macrophage modulation of marbofloxacin in macrophages infected with amastigotes of L. chagasi. Macrophages were collected from peritoneum of BALB/c mice and infected with promastigotes of L. chagasi. After internalization and transformation into amastigotes forms, cells were treated with marbofloxacin in concentration of 100, 500 and 750 μg/mL for 18 hours. The leishmanicidal effect was evaluated by morphological spects of amastigotes inside of macrophages by phagocytosis assay and detection of death amastigotes and macrophages by TUNEL assay. Macrophage modulation was evaluated by release of cytotoxic metabolites and cytokine production. The results showed that L. chagasi-infected macrophages treated with the highest concentration of the drug showed lower amount of amastigotes into the macrophages (p<0,0632) than untreated infected cells. There was pronounced presence of cellular vacuoles in the treated infected-cells, and more apoptotic amastigotes in alive macrophages. It was observed decreased levels of H2O2, IL-1β, IL-6, and TNF-α dose-dependent of marbofloxacin in infected macrophages. The results indicate the leishmanicidal effect of marbofloxacin in infected macrophages and immunomodulation actions in these cells.

References

1. Maia-Elkhoury ANS, Alves WA, Souza-Gomes ML, Sena JM, Luna EA. Visceral leishmaniasis in Brazil: trends and challenges. Cad. Saúde Pública. 2008;24 (12):2941-2947.
2. WHO. Leishmaniasis. World Health Organization. Accessed in: March 2015. Avaiable in: http://www.who.int/mediacentre/factsheets/fs375/en/.
3. Neves DP. Parasitologia humana. 2011;12 ed. São Paulo: Atheneu.
4. Ross, R. Notes on the bodies recently described by Leishman and Donavan. Br. Med. J. 1903;2(2237):1261-1262.
5. Troncarelli MZ, Carneiro DMVF, Langoni H. Visceral Leishmaniasis: An Old Disease with Continuous Impact on Public Health. In: MORALES, J.L. Zoonosis. Rijeka: intech. 2012;p. 263-282.
6. Antinori S, Schifanella L, Cobellino M. Leishmaniasis: new insights from an old an neglected disease. Eur. J. Clin. Microbiol. Infect. Dis. 2012;31(2):109-18.
7. Zamboni DS And Lima-Junior DS. Inflammasomes in host response to protozoan parasites. Immunological Reviews. 1999;265: 156–171.
8. Kangussu-Marcolino MM, Rosário MMT, Noseda MD, Duarte MER, Ducatti DRB, Cassolato JEF, Iacomini M, Martinez GR, Rocha MEM, Cadena SMSC, Noleto GR. Acid heteropolysaccharides with potent antileishmanial effects. Int. J. Biol. Macromol. 2015;81:165-170.
9. Langoni H. Leishmaniose. In J Megid, MG Ribeiro, AC Paes (eds.) Doenças infecciosas em animais de produção e de companhia. 2016; 1ª ed. Rio de Janeiro: Guanabara Koogan, p.468-478.
10. Baneth G, Solano-Gallego L. Leishmaniosis. In CE Greene (ed.) Infectious Diseases of the dog and cat. 2012; 4th ed., Saint Louis: Elsevier, p.734-749.
11. Noli C, Saridomichelakis MN. An update on the diagnosis and treatment of canine leishmaniosis caused by Leishmania infantum (syn. L. chagasi). The Veterinary Journal. 2014;202:425-435.
12. Vouldoukis I, Rougier S, Dugas B, Pino P, Mazier D, Woehrlè F. Canine visceral leishmaniasis: comparison of in vitro activity of marbofloxacin, meglumineantimoniate and sodium stibogluconate, Vet Parasitol. 2006;135: 137-146.
13. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods. 1983; 65 (1-2): 55-63.
14. Pick E, Mizel D. Rapid microassays for measurement of superoxide and hydrogen peroxide production by macrophages in culture using an automatic enzyme immunoassay reader. J. Immunol. Methods. 1981;46: 211-226.
15. Russo M, Teixeira HC, Marcondes MC, et al. Superoxide independent hydrogen peroxide release by activated macrophages, Braz. J. Med. Biol. Res. 1998; 22: 1271-1273.
16. Green LC, Tannembaum SR, Goldman P. Nitrate synthesis in the germfree and conventional rat. Science. 1981;212(4490): 56-58.
17. Noli C, Auxilia ST. Treatment of canine Old World visceral leishmaniasis: a systematic review. Vet. Dermatol. 2005;16(4): 213-232.
18. Moreno J, Nieto J, Chamizo C, González F, Blanco F, Barker DC, Alvar J. The imune response and PBMC subsets in canine visceral leishmaniasis before, and after chemotherapy. Vet. Immunology and Immunonopathology.1999;71: 181-195.
19. Brasil. Ministério da Agricultura Pecuária e Abastecimento. Nota Técninca nº 023/CPV/DFIP/DAS/MAPA, Brasília, 2008.

Additional Files

Published

2020-11-24

How to Cite

1.
dos Anjos Alvarenga Amante JF, Ribeiro Santos A, Mello Santos B, Bott Mantovan K, Fernandes Joaquim S, Soares Latosinski G, Menozzi BD, Hataka A, Baldini Lucheis S, Venturini J, Langoni H. MARBOFLOXACIN INDUCES LEISHMANICIDAL ACTIVITY AND LESS INFLAMMATORY RESPONSE IN Leishmania chagasi INFECTED MACROPHAGES. RVZ [Internet]. 2020 Nov. 24 [cited 2024 Nov. 21];27:1-11. Available from: https://rvz.emnuvens.com.br/rvz/article/view/510

Issue

Vol. 27 (2020)

Section

Original Articles

License

Licença Creative Commons
Este obra está licenciado com uma Licença Creative Commons Atribuição-NãoComercial 4.0 Internacional.

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