ÍNDICE DE SELETIVIDADE DA Chlorella vulgaris: UMA ANÁLISE PRELIMINAR DO POTENCIAL TERAPÊUTICO PARA A LEISHMANIOSE TEGUMENTAR AMERICANA

2021 ◽  
Author(s):  
Maria Gabriella Nunes de Melo ◽  
Isabelle Barreto da Silva Moreira Reino ◽  
Victor Vaitkevicius Antão de Souza Souza ◽  
Jady Moreira da Silva ◽  
Rayana Carla Silva De Morais ◽  
...  

Introdução: O regime terapêutico utilizado no tratamento da Leishmaniose Tegumentar Americana (LTA) é direcionado apenas para morte do parasito, não exerce influência sobre a resposta imune do hospedeiro (1, 2). Desta forma, é essencial desenvolver novos alvos terapêuticos que possam estabelecer uma modulação entre os perfis Th1 (inflamação/proteção) e Th2 (suscetibilidade a infecção), para uma futura cura clínica (3). Estudos com produtos naturais, como a microalga Chlorella vulgaris (CV), estão sendo considerados promissores por apresentarem potencial para atividades terapêuticas e antiparasitárias (4, 5), com facilidade e baixo custo de produção. Objetivo: Assim, o objetivo deste estudo é avaliar in vitro o preliminar potencial terapêutico da C. vulgaris pela obtenção do Índice de Seletividade (IS). Métodos: O extrato de CV foi obtido após cultivo, por sonicação. Para obtenção do IS, utilizou-se Células Mononucleares do Sangue Periférico (PBMC) de humanos, para a determinação da Concentração Citotóxica de 50% (CC50), pelo método de MTT, e ensaios de concentração inibitória de 50% (IC50), em células promastigotas de Leishmania braziliensis, através de contagem celular por microscopia óptica. Ambos os ensaios foram tratados com o extrato de CV e as drogas de referência (DR) (antimoniato pentavalente [SbV] e miltefosina), em concentrações seriadas entre 1000μg/mL e 62,5μg/mL para a CC50, entre 500μg/mL e 0,1 μg/mL para a IC50. O valor de IS foi determinado pela razão entre a CC50 e IC50. Resultados: Para os ensaios de CC50 em PBMC humano, verificou-se baixa toxidade demostrada pela elevada viabilidade celular com o extrato de CV (999,66μg/ml), quando comparado com as DR (SbV= 412,46μg/ml e Miltefosina=159,49μg/ml). Além disso, a IC50 do extrato de CV (144,93μg/ml) apresentou baixa toxicidade para a L. braziliensis, com dados próximos ao do Sbv (119,76μg/ml), mas a Miltefosina (IC50=1,02μg/mL) apresentou uma maior atividade leishmanicida, porém foi o mais tóxico para células humanas. O IS do extrato de CV (IS=6,9) obteve resultado superior ao do Sbv(IS=3,44), apresentando maior seletividade contra o parasito e menor toxidade para as células humanas, e a miltefosina possui o maior valor, sendo 100 vezes mais seletivo para o parasito. Conclusões: Portanto, com base nos dados obtidos o extrato de CV, não tóxico para células humanas e seletivo contra o parasito, possui potencial para futuros estudos in vivo com base no desenvolvimento de novas terapias contra LTA.

Parasitology ◽  
1997 ◽  
Vol 114 (7) ◽  
pp. 91-99 ◽  
Author(s):  
J. A. URBINA

Inhibitors of sterol and phospholipid biosynthesis in kinetoplastid parasites such as Trypanosoma cruzi, the causative agent of Chagas' disease, and different species of Leishmania have potent and selective activity as chemotherapeutic agents in vitro and in vivo. Recent work with the sterol C14α-demethylase inhibitor D0870, a bis triazole derivative, showed that this compound is capable of inducing radical parasitological cure in murine models of both acute and chronic Chagas' disease. Other inhibitors of this type, such as SCH 56592, have also shown curative, rather than suppressive, activity against T. cruzi in these models. Leishmania species have different susceptibilities to sterol biosynthesis inhibitors, both in vitro and in vivo. Leishmania braziliensis promastigotes, naturally resistant to C14α-demethylase inhibitors such as ketoconazole and D0870, were susceptible to these drugs when used in combination with the squalene epoxidase inhibitor terbinafine. Inhibitors of Δ24(25) sterol methyl transferase have been shown to act as potent antiproliferative agents against Trypanosoma cruzi, both in vitro and in vivo. New inhibitors of this type which show enhanced activity and novel mechanisms of action have been synthesized. Recent work has also demonstrated that this type of enzyme inhibitors can block sterol biosynthesis and cell proliferation in Pneumocystis carinii, a fungal pathogen which had previously been found resistant to other sterol biosynthesis inhibitors. Ajoene, an antiplatelet compound derived from garlic, was shown to have potent antiproliferative activity against epimastigotes and amastigotes of Trypanosoma cruzi in vitro; this activity was associated with a significant alteration of the phospholipid composition of the cells with no significant effects on the sterol content. In addition, alkyllsophospholipids such as ilmofosine, miltefosine and edelfosine have been shown to block the proliferation of T. cruzi and Leishmania and alter both the phospholipid and sterol composition. These results indicate the potential of lipid biosynthesis inhibitors as useful therapeutic agents in the treatment of leishmaniasis and Chagas' disease.


2020 ◽  
Vol Volume 15 ◽  
pp. 8659-8672
Author(s):  
Jéssica Rebouças-Silva ◽  
Maraine Catarina Tadini ◽  
Danielle Devequi-Nunes ◽  
Ana Luíza Mansur ◽  
Paulo S Silveira-Mattos ◽  
...  

1998 ◽  
Vol 70 (4) ◽  
pp. 363-366 ◽  
Author(s):  
H Komaki ◽  
M Yamashita ◽  
Y Niwa ◽  
Y Tanaka ◽  
N Kamiya ◽  
...  
Keyword(s):  

Parasitology ◽  
2017 ◽  
Vol 144 (13) ◽  
pp. 1783-1790 ◽  
Author(s):  
ALVARO MARTIN-MONTES ◽  
MERY SANTIVAÑEZ-VELIZ ◽  
ELSA MORENO-VIGURI ◽  
RUBÉN MARTÍN-ESCOLANO ◽  
CARMEN JIMÉNEZ-MONTES ◽  
...  

SUMMARYLeishmaniasis is one of the world's most neglected diseases, and it has a worldwide prevalence of 12 million. There are no effective human vaccines for its prevention, and treatment is hampered by outdated drugs. Therefore, research aiming at the development of new therapeutic tools to fight leishmaniasis remains a crucial goal today. With this purpose in mind, we present 20 arylaminoketone derivatives with a very interesting in vitro and in vivo efficacy against Trypanosoma cruzi that have now been studied against promastigote and amastigote forms of Leishmania infantum, Leishmania donovani and Leishmania braziliensis strains. Six out of the 20 Mannich base-type derivatives showed Selectivity Index between 39 and 2337 times higher in the amastigote form than the reference drug glucantime. These six derivatives affected the parasite infectivity rates; the result was lower parasite infectivity rates than glucantime tested at an IC25 dose. In addition, these derivatives were substantially more active against the three Leishmania species tested than glucantime. The mechanism of action of these compounds has been studied, showing a greater alteration in glucose catabolism and leading to greater levels of iron superoxide dismutase inhibition. These molecules could be potential candidates for leishmaniasis chemotherapy.


2009 ◽  
Vol 77 (7) ◽  
pp. 2948-2956 ◽  
Author(s):  
Diego A. Vargas-Inchaustegui ◽  
Wendy Tai ◽  
Lijun Xin ◽  
Alison E. Hogg ◽  
David B. Corry ◽  
...  

ABSTRACT We have previously reported that Leishmania braziliensis infection can activate murine dendritic cells (DCs) and upregulate signaling pathways that are essential for the initiation of innate immunity. However, it remains unclear whether Toll-like receptors (TLRs) are involved in L. braziliensis-mediated DC activation. To address this issue, we generated bone marrow-derived DCs from MyD88−/− and TLR2−/− mice and examined their responsiveness to parasite infection. While wild-type DCs were efficiently activated to produce cytokines and prime naïve CD4+ T cells, L. braziliensis-infected MyD88−/− DCs exhibited less activation and decreased production of interleukin-12 (IL-12) p40. Furthermore, MyD88−/− mice were more susceptible to infection in that they developed larger and prolonged lesions compared to those in control mice. In sharp contrast, the lack of TLR2 resulted in an enhanced DC activation and increased IL-12 p40 production after infection. As such, L. braziliensis-infected TLR2−/− DCs were more competent in priming naïve CD4+ T cells in vitro than were their controls, findings which correlated with an increased gamma interferon production in vivo and enhanced resistance to infection. Our results suggest that while MyD88 is indispensable for the generation of protective immunity to L. braziliensis, TLR2 seems to have a regulatory role during infection.


1990 ◽  
Vol 43 (6) ◽  
pp. 623-631 ◽  
Author(s):  
J. A. Rey ◽  
N. G. Saravia ◽  
B. L. Travi ◽  
A. Z. Valencia

Author(s):  
Amanda Fonseca Perestrelo ◽  
Selma Giorgio ◽  
Aline Parolin Calarga ◽  
Marcelo Brocchi ◽  
Kamila Cristina Silva Krywacz ◽  
...  

Leishmania braziliensis é a principal espécie causadora da leishmaniose mucocutânea, caracterizada por fases cutânea e mucosa. A doença é transmitida pela fêmea de flebotominíneos e acomete toda a América do Sul. As pesquisas relacionadas a esse parasita são escassas e, visto que é o mais incidente no Brasil, decidiu-se introduzi-lo e estudá-lo no Laboratório de Leishmaniose, padronizando técnicas de cultivo e analisando infecções in vitro e in vivo.


Marine Drugs ◽  
2021 ◽  
Vol 20 (1) ◽  
pp. 9
Author(s):  
Ana Regueiras ◽  
Álvaro Huguet ◽  
Tiago Conde ◽  
Daniela Couto ◽  
Pedro Domingues ◽  
...  

Microalgae are known as a producer of proteins and lipids, but also of valuable compounds for human health benefits (e.g., polyunsaturated fatty acids (PUFAs); minerals, vitamins, or other compounds). The overall objective of this research was to prospect novel products, such as nutraceuticals from microalgae, for application in human health, particularly for metabolic diseases. Chlorella vulgaris and Chlorococcum amblystomatis were grown autotrophically, and C. vulgaris was additionally grown heterotrophically. Microalgae biomass was extracted using organic solvents (dichloromethane, ethanol, ethanol with ultrasound-assisted extraction). Those extracts were evaluated for their bioactivities, toxicity, and metabolite profile. Some of the extracts reduced the neutral lipid content using the zebrafish larvae fat metabolism assay, reduced lipid accumulation in fatty-acid-overloaded HepG2 liver cells, or decreased the LPS-induced inflammation reaction in RAW264.7 macrophages. Toxicity was not observed in the MTT assay in vitro or by the appearance of lethality or malformations in zebrafish larvae in vivo. Differences in metabolite profiles of microalgae extracts obtained by UPLC-LC-MS/MS and GNPS analyses revealed unique compounds in the active extracts, whose majority did not have a match in mass spectrometry databases and could be potentially novel compounds. In conclusion, microalgae extracts demonstrated anti-obesity, anti-steatosis, and anti-inflammatory activities and could be valuable resources for developing future nutraceuticals. In particular, the ultrasound-assisted ethanolic extract of the heterotrophic C. vulgaris significantly enhanced the anti-obesity activity and demonstrated that the alteration of culture conditions is a valuable approach to increase the production of high-value compounds.


PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255996
Author(s):  
Danielli M. M. Dantas ◽  
Thiago B. Cahú ◽  
Carlos Yure B. Oliveira ◽  
Ricardo Abadie-Guedes ◽  
Nathalia A. Roberto ◽  
...  

Recent advances in microalgae biotechnology have proven that these microorganisms contain a number of bioactive molecules, that can be used as food additives that help prevent disease. The green microalga Chlorella vulgaris presents several biomolecules, such as lutein and astaxanthin, with antioxidant capacity, which can play a protective role in tissues. In this study, we produced and analyzed a C. vulgaris functional alcoholic beverage (produced using a traditional Brazilian alcoholic beverage, cachaça, and C. vulgaris biomass). Assays were conducted in vitro by radical scavenging tests, and in vivo, by modeling cortical spreading depression in rat brains. Scavenging radical assays showed that consumption of the C. vulgaris alcoholic beverage had a DPPH inhibition of 77.2%. This functional alcoholic beverage at a concentration of 12.5 g L-1 significantly improved cortical spreading depression velocity in the rat brains (2.89 mm min-1), when compared with cachaça alone (3.68 mm min-1) and control (distilled water; 3.25 mm min-1). Moreover, animals that consumed the functional beverage gained less weight than those that consumed just alcohol and the control groups. These findings suggest that the C. vulgaris functional alcoholic beverage plays a protective physiologic role in protecting brain cells from the effects of drinking ethanol.


2019 ◽  
Vol 137 ◽  
pp. 139-150 ◽  
Author(s):  
Mengen Yu ◽  
Mengjiao Chen ◽  
Jiangli Gui ◽  
Shudan Huang ◽  
Yumeng Liu ◽  
...  

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