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Activity of the sesquiterpene lactone goyazensolide against Trypanosoma cruzi in vitro and in vivo

  • Matheus Marques Milagre (a1), Renata Tupinambá Branquinho (a1), Maira Fonseca Gonçalves (a1), GMP de Assis (a2), Maykon Tavares de Oliveira (a2), LES Reis (a1), Dênia Antunes Saúde-Guimarães (a1) and Marta de Lana (a1) (a2)...

Abstract

Background:

The current drugs for Chagas disease treatment present several limitations

Methods:

The sesquiterpene lactone goyazensolide (GZL) was evaluated regarding to cytotoxicity and trypanocidal activity against amastigotes, selectivity index (SI) in vitro, acute toxicity and anti-Trypanosoma cruzi activity in vivo.

Results:

The in vitro cytotoxicity in H9c2 cells was observed at doses >250 ng mL−1 of GZL and the SI were of 52.82 and 4.85 (24 h) and of 915.00 and 41.00 (48 h) for GZL and BZ, respectively. Nephrotoxicity and hepatotoxicity were not verified. Treatment with GZL of mice infected with CL strain led to a significant decrease of parasitaemia and total survival at doses of 1 and 3 mg kg−1 day−1 by oral and IV, respectively. This last group cured 12.5% of the animals (negativation of HC, PCR, qPCR and ELISA). Animals infected with Y strain showed significant decrease of parasitaemia and higher negativation in all parasitological tests in comparison to BZ and control groups, but were ELISA reactive, as well as the BZ group, but mice treated with 5.0 mg kg−1 day−1 by oral were negative in parasitological tests and survived.

Conclusion:

GZL was more active against T. cruzi than benznidazole in vitro and presented important therapeutic activity in vivo in both T. cruzi strains.

Copyright

Corresponding author

Author for correspondence: Marta de Lana, E-mail: delana@ufop.edu.br

References

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Acuna, UM, Shen, Q, Ren, Y, Lantvit, DD, Wittwer, JA, Kinghorn, AD, Swanson, SM and Carcache de Blanco, EJ (2013) Goyazensolide induces apoptosis in cancer cells in vitro and in vivo. Section Title: Pharmacology 9, 18, 3653.
Andrade, SG, Freitas, LA, Peyrol, S, Pimentel, AR and Sadigursky, M (1991) Experimental chemotherapy of Trypanosoma cruzi infection: persistence of parasite antigens and positive serology in parasitologically cured mice. Bulletin of the World Health Organization 69, 191197.
Avila, HA, Sigman, DS, Cohen, LM, Millikan, RC and Simpson, L (1991) Polymerase chain reaction amplification of Trypanosoma cruzi kinetoplast minicircle DNA isolated from whole blood lysates: diagnosis of chronic Chagas’ disease. Molecular and Biochemical Parasitology 48, 211221.
Bahia, MT, de Diniz, LF and Mosqueira, VCF (2014) Therapeutical approaches under investigation for treatment of Chagas disease. Expert Opinion on Investigational Drugs 23, 12251237.
Bermudez, J, Davies, C, Simonazzi, A, Pablo Real, J and Palma, S (2016) Current drug therapy and pharmaceutical challenges for Chagas disease. Acta Tropica 156, 116.
Bern, C (2015) Chagas’ disease. New England Journal of Medicine 373, 456466.
Bohlmann, F, Zdero, C, Robinson, H and King, RM (1980) Caryophyllene derivatives and a heliangolide from Lychnophora species. Phytochemistry 19, 23812385.
Branquinho, RT, Mosqueira, VCF, Kano, EK, de Souza, J, Dorim, DDR, Saude-Guimaraes, DA and de Lana, M (2014 a) HPLC-DAD and UV-spectrophotometry for the determination of lychnopholide in nanocapsule dosage form: validation and application to release kinetic study. Journal of Chromatographic Science 52, 1926.
Branquinho, RT, Mosqueira, VCF, de Oliveira-Silva, JCV, Simões-Silva, MR, Saúde-Guimarães, DA and de Lana, M (2014 b) Sesquiterpene lactone in nanostructured parenteral dosage form is efficacious in experimental Chagas disease. Antimicrobial Agents and Chemotherapy 58, 20672075.
BRASIL (2004) Ministério da Saúde, Agência Nacional de Vigilância Sanitária. Resolução de Diretoria Colegiada (RDC) n° 48 de 16/03/2004. Diário Oficial da União.
Brener, Z (1962) Therapeutic activity and criterion of cure on mice experimentally infected with Trypanosoma cruzi. Revista do Instituto de Medicina Tropical de Sao Paulo 4, 389396.
Britto, C, Cardoso, MA, Wincker, P and Morel, CM (1993) A simple protocol for the physical cleavage of Trypanosoma cruzi kinetoplast DNA present in blood samples and its use in polymerase chain reaction (PCR)-based diagnosis of chronic Chagas disease. Memórias do Instituto Oswaldo Cruz 88, 171172.
Caldas, S, Caldas, IS, de Diniz, LF, de Lima, WG, de Oliveira, RP, Cecílio, AB, Ribeiro, I, Talvani, A and Bahia, MT (2012) Real-time PCR strategy for parasite quantification in blood and tissue samples of experimental Trypanosoma cruzi infection. Acta Tropica 123, 170177.
Chagas, C (1909) Nova tripanozomiaze humana: estudos sobre a morfolojia e o ciclo evolutivo do Schizotrypanum cruzi n. gen., n. sp., ajente etiolojico de nova entidade morbida do homem. Memórias do Instituto Oswaldo Cruz 1, 159218.
Chiari, E, de Oliveira, AB, Raslan, DS, Mesquita, AAL and Tavares, KG (1991) Screening in vitro of natural products against blood forms of Trypanosoma cruzi. Transactions of the Royal Society of Tropical Medicine and Hygiene 85, 372374.
Chiari, E, Duarte, DS, Raslan, DS, Saúde, DA, Perry, KSP, Boaventura, MAD, Grandi, TSM, Stehmann, JR, Anjos, AMG and De Oliveira, AB (1996) In vitro screening of Asteraceae plant species against Trypanosoma cruzi. Phytotherapy Research 10, 636638.
Coura, JR (2013 a) Chagas disease: control, elimination and eradication. Is it possible? Memorias do Instituto Oswaldo Cruz 108, 962967.
Coura, JR (2013 b) The discovery of Chagas disease (1908-1909): great successes and certain misunderstandings and challenges. Revista da Sociedade Brasileira de Medicina Tropical 46, 389390.
Coura, JR and Borges-Pereira, J (2012) Doença de Chagas. O que é conhecido e o que deve ser melhorado: Uma visão sistêmica. Revista da Sociedade Brasileira de Medicina Tropical 45, 286296.
Coura, JR and de Castro, SL (2002) A critical review on Chagas disease chemotherapy. Memórias do Instituto Oswaldo Cruz 97, 324.
Croft, S, Barrett, M and Urbina, J (2005) Chemotherapy of trypanosomiases and leishmaniasis. Trends in Parasitology 21, 508512.
Cummings, KL and Tarleton, RL (2003) Rapid quantitation of Trypanosoma cruzi in host tissue by real-time PCR. Molecular and Biochemical Parasitology 129, 5359. https://doi.org/10.1016/S0166-6851(03)00093-8.
da Silva, CF, da Batista, DGJ, De Araújo, JS, Batista, MM, Lionel, J, de Souza, EM, Hammer, ER, da Silva, PB, De Mieri, M, Adams, M, Zimmermann, S, Hamburger, M, Brun, R, Schühly, W and de Soeiro, MNC (2013) Activities of psilostachyn A and cynaropicrin against Trypanosoma cruzi in vitro and in vivo. Antimicrobial Agents and Chemotherapy 57, 53075314.
De Lana, M and Martins-Filho, OA (2015) Revisiting the posttherapeutic cure criterion in Chagas disease: time for new methods, more questions, doubts, and polemics or time to change old concepts? BioMed Research International 2015, 110.
de Oliveira, MT, Branquinho, RT, Alessio, GD, Mello, CGC, Nogueira-de-Paiva, NC, Carneiro, CM, de Toledo, MJO, Reis, AB, Martins-Filho, OAM and de Lana, M (2017) Tci, TcII and TcVI Trypanosoma cruzi samples from Chagas disease patients with distinct clinical forms and critical analysis of in vitro and in vivo behavior, response to treatment and infection evolution in murine model. Acta Tropica 167, 108120.
Dias, JCP, Novaes Ramos, A, Dias Gontijo, E, Luquetti, A, Aparecida Shikanai-Yasuda, M, Rodrigues Coura, J, Morais Torres, R, Renan da Cunha Melo, J, Antonio de Almeida, E, de Oliveira, W Jr, Carlos Silveira, A, Marcondes de Rezende, J, Scalabrini Pinto, F, Walter Ferreira, A, Rassi, A, Augusto Fragata Filho, A, Silvestre de Sousa, A, Correia Filho, D, Maria Jansen, A, Manzan Queiroz Andrade, G, Felícia De Paoli de Carvalho Britto, C, Yecê das Neves Pinto, A, Rassi, A Jr, Elisabeth Campos, D, Abad-Franch, F, Eloi Santos, S, Chiari, E, Marcel Hasslocher-Moreno, A, Furtado Moreira, E, Seila de Oliveira Marques, D, Seila de Oliveira Marques, D, Lages Silva, E, Antonio Marin-Neto, J, Maria da Cunha Galvão, L, Salles Xavier, S, Aldo da Silva Valente, S, Barbosa Carvalho, N, Viana Cardoso, A, Albuquerque e Silva, R, Maia da Costa, V, Monzani Vivaldini, S, Mamede Oliveira, S, da Costa Valente, V, Maia Lima, M and Vieira Alves, R (2016) II consenso Brasileiro em Doença de Chagas, 2015. Epidemiologia e Serviços de Saúde 25, 110.
Filardi, LS and Brener, Z (1987) Susceptibility and natural resistance of Trypanosoma cruzi strains to drugs used clinically in Chagas disease. Transactions of the Royal Society of Tropical Medicine and Hygiene 81, 755759.
Gomes, ML, Macedo, AM, Vago, AR, Pena, SDJ, Galvão, LMC and Chiari, E (1998) Trypanosoma cruzi: optimization of polymerase chain reaction for detection in human blood. Experimental Parasitology 88, 2833.
Guedes, P, Fietto, J, Lana, M and Bahia, M (2008) Advances in Chagas disease chemotherapy. Anti-Infective Agents in Medicinal Chemistry 5, 175186.
Guedes-da-Silva, FH, Batista, DGJ, Meuser, MB, Demarque, KC, Fulco, TO, Araújo, JS, Da Silva, PB, Da Silva, CF, Patrick, DA, Bakunova, SM, Bakunov, SA, Tidwell, RR, Oliveira, GM, Britto, C, Moreira, OC and Soeiro, MNC (2016) In Vitro and In vivo trypanosomicidal action of novel arylimidamides against Trypanosoma cruzi. Antimicrobial Agents and Chemotherapy 60, 24252434.
Krettli, AU (2009) The utility of anti-trypomastigote lytic antibodies for determining cure of Trypanosoma cruzi infections in treated patients: an overview and perspectives. Memórias do Instituto Oswaldo Cruz 104, 142151.
Krettli, AU, Brener, Z and Cançado, JR (1982) Effect of specific chemotherapy on the levels of lytic antibodies in Chagas's disease. Transactions of the Royal Society of Tropical Medicine and Hygiene 76, 334340.
Martins, HR, Figueiredo, LM, Valamiel-silva, JCO, Carneiro, CM, Machado-Coelho, GLL, Vitelli-Avelar, DM, Bahia, MT, Martins-Filho, OA, Macedo, AM and Lana, M (2008) Persistence of PCR-positive tissue in benznidazole-treated mice with negative blood parasitological and serological tests in dual infections with Trypanosoma cruzi stocks from different genotypes. Journal of Antimicrobial Chemotherapy 61, 13191327.
Martins-Filho, OA, Pereira, ME, Carvalho, JF, Cançado, JR and Brener, Z (1995) Flow cytometry, a new approach to detect anti-live trypomastigote antibodies and monitor the efficacy of specific treatment in human Chagas’ disease. Clinical and Diagnostic Laboratory Immunology 2, 569573.
Mello, CGC, Branquinho, RT, Oliveira, MT, Milagre, MM, Saúde-Guimarães, DA, Mosqueira, VCF and de Lana, M (2016) Efficacy of lychnopholide polymeric nanocapsules after oral and intravenous administration in murine experimental Chagas disease. Antimicrobial Agents and Chemotherapy 60, 52155222.
Mosmann, T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of Immunological Methods 65, 5563.
Nwaka, S and Hudson, A (2006) Innovative lead discovery strategies for tropical diseases. Nature Reviews Drug Discovery 5, 941955.
O'Neill, LA and Kaltschmidt, C (1997) NF-kappa B: a crucial transcription factor for glial and neuronal cell function. Trends in Neurosciences 20, 252258.
OECD/OCDE (2001) Acute oral toxicity – acute toxic class method. Guideline for Testing of Chemicals 423, 114.
Oliveira, AB, Saúde, DA, Perry, KSP, Duarte, DS, Raslan, DS, Boaventura, MAD and Chiari, E (1996) Trypanocidal sesquiterpenes from Lychnophora species. Phytotherapy Research 10, 292295.
Pérez-Molina, JA, Perez, AM, Norman, FF, Monge-Maillo, B and López-Vélez, R (2015) Old and new challenges in Chagas disease. The Lancet Infectious Diseases 15, 13471356.
Romanha, AJ, De Castro, SL, Soeiro, MDNC, Lannes-Vieira, J, Ribeiro, I, Talvani, A, Bourdin, B, Blum, B, Olivieri, B, Zani, C, Spadafora, C, Chiari, E, Chatelain, E, Chaves, G, Calzada, JE, Bustamante, JM, Freitas-Junior, LH, Romero, LI, Bahia, MT, Lotrowska, M, Soares, M, Andrade, SG, Armstrong, T, Degrave, W and Andrade, ZDA (2010) In vitro and in vivo experimental models for drug screening and development for Chagas disease. Memórias do Instituto Oswaldo Cruz 105, 233238.
Salem, MM and Werbovetz, KA (2006) Natural products from plants as drug candidates and lead compounds against leishmaniasis and trypanosomiasis. Current Medicinal Chemistry 13, 25712598.
Santos, LS, Torres, RM, Machado-de-Assis, GF, Bahia, MT, Martins, HR, Teixeira-Carvalho, A, Coelho-dos-Reis, JGA, Albajar-Viñas, P, Martins-Filho, OA and de Lana, M (2012) In-house ELISA method to analyze anti-Trypanosoma cruzi IgG reactivity for differential diagnosis and evaluation of Chagas disease morbidity. Revista da Sociedade Brasileira de Medicina Tropical 45, 3544.
Schmidt, TJ, Da Costa, FB, Lopes, NP, Kaiser, M and Brun, R (2013) In silico prediction and experimental evaluation of furanoheliangolide sesquiterpene lactones as potent agents against Trypanosoma brucei rhodesiense. Antimicrobial Agents and Chemotherapy 58, 325-332. https://aac.asm.org/content/58/1/325.
Schmunis, GA and Yadon, ZE (2010) Chagas disease: a Latin American health problem becoming a world health problem. Acta Tropica 115, 1421.
Sulsen, VP, Frank, FM, Cazorla, SI, Anesini, CA, Malchiodi, EL, Freixa, B, Vila, R, Muschietti, LV and Martino, VS (2008) Trypanocidal and leishmanicidal activities of sesquiterpene lactones from Ambrosia tenuifolia sprengel (Asteraceae). Antimicrobial Agents and Chemotherapy 52, 24152419.
Sulsen, VP, Cazorla, SI, Frank, FM, Laurella, LC, Muschietti, LV, Catalán, CA, Martino, VS and Malchiodi, EL (2013) Natural terpenoids from ambrosia species are active in vitro and in vivo against human pathogenic trypanosomatids. PLoS Neglected Tropical Diseases 7, e2494.
Ugoline, BCA, de Souza, J, Ferrari, FC, Ferraz-Filha, ZS, Coelho, GB and Saúde-Guimarães, DA (2017) The influence of seasonality on the content of goyazensolide and on anti-inflammatory and anti-hyperuricemic effects of the ethanolic extract of Lychnophora passerina (Brazilian arnica). Journal of Ethnopharmacology 198, 444450.
Urbina, JA (2009) New advances in the management of a long-neglected disease. Clinical Infectious Diseases 49, 16851687.
Vitelli-Avelar, DM, Sathler-Avelar, R, Wendling, APB, Rocha, RDR, Teixeira-Carvalho, A, Martins, , Dias, JCP, Rassi, A, Luquetti, AO, Elói-Santos, SM and Martins-Filho, OA (2007) Non-conventional flow cytometry approaches to detect anti-Trypanosoma cruzi immunoglobulin G in the clinical laboratory. Journal of Immunological Methods 318, 102112.
Voller, A, Bidwell, DE and Bartlett, A (1976) Enzyme immunoassays in diagnostic medicine. Theory and practice. Bulletin of the World Health Organization 53, 5565.
Wendling, APB, Vitelli-Avelar, DM, Sathler-Avelar, R, Geiger, SM, Teixeira-Carvalho, A, Gontijo, ED, Elói-Santos, SM and Martins-Filho, OA (2011) The use of IgG antibodies in conventional and non-conventional immunodiagnostic tests for early prognosis after treatment of Chagas disease. Journal of Immunological Methods 370, 2434.
WHO (2018) Chagas disease – american trypanosomiasis. Polish Annals of Medicine 18, 156167.
Zimmermann, S, Thomi, S, Kaiser, M, Hamburger, M and Adams, M (2012) Screening and HPLC-based activity profiling for new antiprotozoal leads from European plants. Scientia Pharmaceutica 80, 205213.
Zingales, B, Andrade, S, Briones, M, Campbell, D, Chiari, E, Fernandes, O, Guhl, F, Lages-Silva, E, Macedo, A, Machado, C, Miles, M, Romanha, A, Sturm, N, Tibayrenc, M and Schijman, A (2009) A new consensus for Trypanosoma cruzi intraspecific nomenclature: second revision meeting recommends TcI to TcVI. Memórias do Instituto Oswaldo Cruz 104, 10511054.

Keywords

Activity of the sesquiterpene lactone goyazensolide against Trypanosoma cruzi in vitro and in vivo

  • Matheus Marques Milagre (a1), Renata Tupinambá Branquinho (a1), Maira Fonseca Gonçalves (a1), GMP de Assis (a2), Maykon Tavares de Oliveira (a2), LES Reis (a1), Dênia Antunes Saúde-Guimarães (a1) and Marta de Lana (a1) (a2)...

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