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Trichomonas vaginalis NTPDase inhibited by lycorine modulates the parasite-neutrophil interaction.
Parasitol Res. 2020 Aug; 119(8):2587-2595.PR

Abstract

Lycorine is an Amaryllidaceae alkaloid that presents anti-Trichomonas vaginalis activity. T. vaginalis causes trichomoniasis, the most common non-viral sexually transmitted infection. The modulation of T. vaginalis purinergic signaling through the ectonucleotidases, nucleoside triphosphate diphosphohydrolase (NTPDase), and ecto-5'-nucleotidase represents new targets for combating the parasite. With this knowledge, the aim of this study was to investigate whether NTPDase and ecto-5'-nucleotidase inhibition by lycorine could lead to extracellular ATP accumulation. Moreover, the lycorine effect on the reactive oxygen species (ROS) production by neutrophils and parasites was evaluated as well as the alkaloid toxicity. The metabolism of purines was assessed by HPLC. ROS production was measured by flow cytometry. Cytotoxicity against epithelial vaginal cells and fibroblasts was tested, as well as the hemolytic effect of lycorine and its in vivo toxicity in Galleria mellonella larvae. Our findings showed that lycorine caused ATP accumulation due to NTPDase inhibition. The alkaloid did not affect the ROS production by T. vaginalis; however, it increased ROS levels in neutrophils incubated with lycorine-treated trophozoites. Lycorine was cytotoxic against vaginal epithelial cells and fibroblasts; conversely, it was not hemolytic neither exhibited toxicity against the in vivo model of G. mellonella larvae. Overall, besides having anti-T. vaginalis activity, lycorine modulates ectonucleotidases and stimulates neutrophils to secrete ROS. This mechanism of action exerted by the alkaloid could enhance the susceptibility of T. vaginalis to host immune cell, contributing to protozoan clearance.

Authors+Show Affiliations

Laboratório de Pesquisa em Parasitologia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, Porto Alegre, RS, 90610-000, Brazil.Laboratório de Pesquisa em Parasitologia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, Porto Alegre, RS, 90610-000, Brazil.Departamento de Ciências Básicas da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil.Laboratório de Biofilmes e Diversidade Microbiana, Faculdade de Farmácia e Centro de Biotecnologia, Universidade do Rio Grande do Sul, Porto Alegre, RS, Brazil.Laboratório de Toxicologia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.Laboratório de Farmacognosia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.Laboratório de Farmacognosia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.Laboratório de Toxicologia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.Departamento de Química, Universidade Federal do Espírito Santo, Vitória, ES, Brazil.Laboratório de Farmacognosia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.Laboratório de Pesquisa em Parasitologia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, Porto Alegre, RS, 90610-000, Brazil. tiana.tasca@ufrgs.br.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32524267

Citation

Petró-Silveira, Brenda, et al. "Trichomonas Vaginalis NTPDase Inhibited By Lycorine Modulates the Parasite-neutrophil Interaction." Parasitology Research, vol. 119, no. 8, 2020, pp. 2587-2595.
Petró-Silveira B, Rigo GV, da Silva Trentin D, et al. Trichomonas vaginalis NTPDase inhibited by lycorine modulates the parasite-neutrophil interaction. Parasitol Res. 2020;119(8):2587-2595.
Petró-Silveira, B., Rigo, G. V., da Silva Trentin, D., Macedo, A. J., Sauer, E., de Oliveira Alves, E., Tallini, L. R., Garcia, S. C., de Souza Borges, W., Zuanazzi, J. Â. S., & Tasca, T. (2020). Trichomonas vaginalis NTPDase inhibited by lycorine modulates the parasite-neutrophil interaction. Parasitology Research, 119(8), 2587-2595. https://doi.org/10.1007/s00436-020-06739-8
Petró-Silveira B, et al. Trichomonas Vaginalis NTPDase Inhibited By Lycorine Modulates the Parasite-neutrophil Interaction. Parasitol Res. 2020;119(8):2587-2595. PubMed PMID: 32524267.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Trichomonas vaginalis NTPDase inhibited by lycorine modulates the parasite-neutrophil interaction. AU - Petró-Silveira,Brenda, AU - Rigo,Graziela Vargas, AU - da Silva Trentin,Danielle, AU - Macedo,Alexandre José, AU - Sauer,Elisa, AU - de Oliveira Alves,Elen, AU - Tallini,Luciana Ruschel, AU - Garcia,Solange Cristina, AU - de Souza Borges,Warley, AU - Zuanazzi,José Ângelo Silveira, AU - Tasca,Tiana, Y1 - 2020/06/11/ PY - 2020/02/19/received PY - 2020/05/31/accepted PY - 2020/6/12/pubmed PY - 2020/6/12/medline PY - 2020/6/12/entrez KW - Amaryllidaceae KW - Galleria mellonella KW - Lycorine KW - NTPDase KW - Reactive oxygen species KW - Trichomonas vaginalis SP - 2587 EP - 2595 JF - Parasitology research JO - Parasitol. Res. VL - 119 IS - 8 N2 - Lycorine is an Amaryllidaceae alkaloid that presents anti-Trichomonas vaginalis activity. T. vaginalis causes trichomoniasis, the most common non-viral sexually transmitted infection. The modulation of T. vaginalis purinergic signaling through the ectonucleotidases, nucleoside triphosphate diphosphohydrolase (NTPDase), and ecto-5'-nucleotidase represents new targets for combating the parasite. With this knowledge, the aim of this study was to investigate whether NTPDase and ecto-5'-nucleotidase inhibition by lycorine could lead to extracellular ATP accumulation. Moreover, the lycorine effect on the reactive oxygen species (ROS) production by neutrophils and parasites was evaluated as well as the alkaloid toxicity. The metabolism of purines was assessed by HPLC. ROS production was measured by flow cytometry. Cytotoxicity against epithelial vaginal cells and fibroblasts was tested, as well as the hemolytic effect of lycorine and its in vivo toxicity in Galleria mellonella larvae. Our findings showed that lycorine caused ATP accumulation due to NTPDase inhibition. The alkaloid did not affect the ROS production by T. vaginalis; however, it increased ROS levels in neutrophils incubated with lycorine-treated trophozoites. Lycorine was cytotoxic against vaginal epithelial cells and fibroblasts; conversely, it was not hemolytic neither exhibited toxicity against the in vivo model of G. mellonella larvae. Overall, besides having anti-T. vaginalis activity, lycorine modulates ectonucleotidases and stimulates neutrophils to secrete ROS. This mechanism of action exerted by the alkaloid could enhance the susceptibility of T. vaginalis to host immune cell, contributing to protozoan clearance. SN - 1432-1955 UR - https://www.unboundmedicine.com/medline/citation/32524267/Trichomonas_vaginalis_NTPDase_inhibited_by_lycorine_modulates_the_parasite-neutrophil_interaction L2 - https://dx.doi.org/10.1007/s00436-020-06739-8 DB - PRIME DP - Unbound Medicine ER -
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