In Vitro Leishmanicidal Activity of Copaiba Oil and Kojic Acid Combination on the Protozoan Leishmania (Leishmania) amazonensis and Host Cell

Author:

Moraes Lienne Silveira de123,Galué-Parra Adan Jesús2ORCID,Hage Amanda Anastácia Pinto23,Moura Hévila Aragão2,Garcia Marcus Savio Araujo2,Macêdo Caroline Gomes2,Rodrigues Ana Paula Drummond34ORCID,Guilhon Giselle Maria Skelding Pinheiro5,Silva Edilene Oliveira da23ORCID

Affiliation:

1. Pharmaceutical Sciences Post Graduation Program, Health and Biological Sciences Department, Federal University of Amapa (UNIFAP), Macapa 68903-419, AP, Brazil

2. Laboratory of Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil

3. National Institute of Science and Technology in Structural Biology and Bioimaging, Rio de Janeiro 21040-900, RJ, Brazil

4. Laboratory of Electron Microscopy, Evandro Chagas’s Institute, Department of Health Surveillance, Ministry of Health, Belém 70723-040, PA, Brazil

5. Institute of Exact and Natural Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil

Abstract

(1) Background: Leishmaniasis refers to a group of anthropozoonotic diseases caused by Leishmania. The major chemotherapeutic agent used for its treatment is Glucantime®®, but the search continues for new compounds that are economically viable and act on the protozoan without causing damage to the host cell. As an alternative approach, this study used a combination of copaiba oil (CO) and kojic acid (KA) to determine their in vitro action on host cells, on the Leishmania (Leishmania) amazonensis protozoan and its interaction with macrophages. (2) Methods: In vitro culture, analysis of cytokine release and microscopy assays were performed. Statistical analysis was performed with ANOVA (GraphPad Prism). (3) Results: The combination did not induce cytotoxic effects on macrophages after treatment but promoted morphological changes in the protozoan, such as nuclear alterations (apoptotic characteristics), alterations in the cellular body and an increase in the number of electrodense structures and acidocalcisomes, observed mainly at the concentrations of CO20KA50 and CO30KA50 μg/mL. We observed reductions in the intracellular amastigote number and in the production of proinflammatory cytokines, such as IL-6 and TNF-α, after treatment with CO30KA at 50 µg/mL. (4) Conclusions: We report here, for the first time, that the combination of CO and KA may be a promising approach against Leishmania (Leishmania) amazonensis.

Funder

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)- Finance Code 001, FAPESPA, PROPESP-UFPA

Instituto Nacional de Biologia Estrutural e Bioimagem-INBEB

Publisher

MDPI AG

Subject

Virology,Microbiology (medical),Microbiology

Reference55 articles.

1. PAHO (2023, September 22). Pan American Health Organization (2022). Leishmaniasis. Key Facts. Updated January 2022. Available online: https://www.paho.org/en/topics/leishmaniasis.

2. WHO (2023, September 22). World Health Organization (2023). Control of the Leishmaniases. Fact Sheets. Updated January 2023. Available online: http://www.who.int/mediacentre/factsheets/fs375/en/.

3. BRASIL (2023, September 20). Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância Epidemiológica. Casos de Leishmaniose Tegumentar. Brasil, Grandes Regiões e Unidades Federadas. 1990 a 2020 Brasília/DF, 202, Available online: https://www.gov.br/saude/pt-br/media/pdf/2021/novembro/17/lt-casos.pdf.

4. Cutaneous leishmaniasis: A 2022 updated narrative review into diagnosis and management developments;Schallig;Am. J. Clin. Dermatol.,2022

5. The role of monocytes/macrophages in Leishmania infection: A glance at the human response;Acta Trop.,2020

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