Antileishmanial effects of γCdcPLI, a phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum, on Leishmania (Leishmania) amazonensis.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2023-11-27 eCollection Date: 2023-01-01 DOI:10.1590/0074-02760220225

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

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引用次数: 0

Abstract

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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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。

背景:利什曼病是由利什曼原虫引起的一种被忽视的疾病，除了不断出现耐药寄生虫的报道外，还使用毒性高且疗效有限的药物进行治疗。在这种情况下，蛇血清成为很好的候选者，因为它们是具有产生新药潜力的天然来源。目的:研究从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(Leishmania)的抗利什曼原虫作用。方法:将原毛菌暴露于γCdcPLI环境中，观察其生存能力、细胞周期、侵袭和增殖情况。研究结果:尽管γCdcPLI对巨噬细胞的细胞毒性作用较低，但我们的数据表明，在最高剂量下，γCdcPLI对寄生虫有直接作用，促进G1期阻滞和G2/M期减少。此外，这种PLA2抑制剂在前毛菌预处理时降低了寄生虫的传染性。此外，我们还证明了γCdcPLI处理调节了宿主细胞环境，损害了寄生的早期和后期阶段。主要结论:γCdcPLI是发现利什曼病新靶点的重要工具，也是提高利什曼病治疗效果的替代化合物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464