Marina Neves Gonçalves, Daiana Silva Lopes, Samuel Cota Teixeira, Thaise Lara Teixeira, Vitor de Freitas, Tássia Rafaella Costa, Sarah Natalie Cirilo Gimenes, Isabella Mitie de Camargo, Guilherme de Souza, Marcelo Santos da Silva, Fernanda Van Petten de Vasconcelos Azevedo, Kathleen Fernandes Grego, Luísa Carregosa Santos, Vinícius Queiroz Oliveira, Claudio Vieira da Silva, Renata Santos Rodrigues, Kelly Aparecida Geraldo Yoneyama, Patricia Bianca Clissa, Veridiana de Melo Rodrigues
{"title":"从Crotalus durissus collilineatus蛇血清中提取的磷脂酶A2抑制剂γCdcPLI对亚马孙利什曼原虫的抗利什曼原虫作用。","authors":"Marina Neves Gonçalves, Daiana Silva Lopes, Samuel Cota Teixeira, Thaise Lara Teixeira, Vitor de Freitas, Tássia Rafaella Costa, Sarah Natalie Cirilo Gimenes, Isabella Mitie de Camargo, Guilherme de Souza, Marcelo Santos da Silva, Fernanda Van Petten de Vasconcelos Azevedo, Kathleen Fernandes Grego, Luísa Carregosa Santos, Vinícius Queiroz Oliveira, Claudio Vieira da Silva, Renata Santos Rodrigues, Kelly Aparecida Geraldo Yoneyama, Patricia Bianca Clissa, Veridiana de Melo Rodrigues","doi":"10.1590/0074-02760220225","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Leishmaniasis, a neglected disease caused by the parasite Leishmania, is treated with drugs associated with high toxicity and limited efficacy, in addition to constant reports of the emergence of resistant parasites. In this context, snake serums emerge as good candidates since they are natural sources with the potential to yield novel drugs.</p><p><strong>Objectives: </strong>We aimed to show the antileishmanial effects of γCdcPLI, a phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum, against Leishmania (Leishmania) amazonensis.</p><p><strong>Methods: </strong>Promastigotes forms were exposed to γCdcPLI, and we assessed the parasite viability and cell cycle, as well as invasion and proliferation assays.</p><p><strong>Findings: </strong>Despite the low cytotoxicity effect on macrophages, our data indicate that γCdcPLI has a direct effect on parasites promoting an arrest in the G1 phase and reduction in the G2/M phase at the highest dose tested. Moreover, this PLA2 inhibitor reduced the parasite infectivity when promastigotes were pre-treated. Also, we demonstrated that the γCdcPLI treatment modulated the host cell environment impairing early and late steps of the parasitism.</p><p><strong>Main conclusions: </strong>γCdcPLI is an interesting tool for the discovery of new essential targets on the parasite, as well as an alternative compound to improve the effectiveness of the leishmaniasis treatment.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10690931/pdf/","citationCount":"0","resultStr":"{\"title\":\"Antileishmanial effects of γCdcPLI, a phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum, on Leishmania (Leishmania) amazonensis.\",\"authors\":\"Marina Neves Gonçalves, Daiana Silva Lopes, Samuel Cota Teixeira, Thaise Lara Teixeira, Vitor de Freitas, Tássia Rafaella Costa, Sarah Natalie Cirilo Gimenes, Isabella Mitie de Camargo, Guilherme de Souza, Marcelo Santos da Silva, Fernanda Van Petten de Vasconcelos Azevedo, Kathleen Fernandes Grego, Luísa Carregosa Santos, Vinícius Queiroz Oliveira, Claudio Vieira da Silva, Renata Santos Rodrigues, Kelly Aparecida Geraldo Yoneyama, Patricia Bianca Clissa, Veridiana de Melo Rodrigues\",\"doi\":\"10.1590/0074-02760220225\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Leishmaniasis, a neglected disease caused by the parasite Leishmania, is treated with drugs associated with high toxicity and limited efficacy, in addition to constant reports of the emergence of resistant parasites. In this context, snake serums emerge as good candidates since they are natural sources with the potential to yield novel drugs.</p><p><strong>Objectives: </strong>We aimed to show the antileishmanial effects of γCdcPLI, a phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum, against Leishmania (Leishmania) amazonensis.</p><p><strong>Methods: </strong>Promastigotes forms were exposed to γCdcPLI, and we assessed the parasite viability and cell cycle, as well as invasion and proliferation assays.</p><p><strong>Findings: </strong>Despite the low cytotoxicity effect on macrophages, our data indicate that γCdcPLI has a direct effect on parasites promoting an arrest in the G1 phase and reduction in the G2/M phase at the highest dose tested. Moreover, this PLA2 inhibitor reduced the parasite infectivity when promastigotes were pre-treated. Also, we demonstrated that the γCdcPLI treatment modulated the host cell environment impairing early and late steps of the parasitism.</p><p><strong>Main conclusions: </strong>γCdcPLI is an interesting tool for the discovery of new essential targets on the parasite, as well as an alternative compound to improve the effectiveness of the leishmaniasis treatment.</p>\",\"PeriodicalId\":2,\"journal\":{\"name\":\"ACS Applied Bio Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2023-11-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10690931/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Bio Materials\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1590/0074-02760220225\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"MATERIALS SCIENCE, BIOMATERIALS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1590/0074-02760220225","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
Antileishmanial effects of γCdcPLI, a phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum, on Leishmania (Leishmania) amazonensis.
Background: Leishmaniasis, a neglected disease caused by the parasite Leishmania, is treated with drugs associated with high toxicity and limited efficacy, in addition to constant reports of the emergence of resistant parasites. In this context, snake serums emerge as good candidates since they are natural sources with the potential to yield novel drugs.
Objectives: We aimed to show the antileishmanial effects of γCdcPLI, a phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum, against Leishmania (Leishmania) amazonensis.
Methods: Promastigotes forms were exposed to γCdcPLI, and we assessed the parasite viability and cell cycle, as well as invasion and proliferation assays.
Findings: Despite the low cytotoxicity effect on macrophages, our data indicate that γCdcPLI has a direct effect on parasites promoting an arrest in the G1 phase and reduction in the G2/M phase at the highest dose tested. Moreover, this PLA2 inhibitor reduced the parasite infectivity when promastigotes were pre-treated. Also, we demonstrated that the γCdcPLI treatment modulated the host cell environment impairing early and late steps of the parasitism.
Main conclusions: γCdcPLI is an interesting tool for the discovery of new essential targets on the parasite, as well as an alternative compound to improve the effectiveness of the leishmaniasis treatment.
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