Débora B. Scariot, Elizandra A. Britta, Amanda L. Moreira, Hugo Falzirolli, Cleuza C. Silva, Tânia Ueda-Nakamura, Benedito P. Dias-Filho, Celso V. Nakamura
Abstract
Drug combination therapy is a current trend to treat complex diseases. Many benefits are expected from this strategy, such as cytotoxicity decrease, retardation of resistant strains development, and activity increment. This study evaluated in vitro combination between an innovative thiosemicarbazone molecule - BZTS with miltefosine, a drug already consolidated in the leishmaniasis treatment, against Leishmania amazonensis. Cytotoxicity effects were also evaluated on macrophages and erythrocytes. Synergistic antileishmania effect and antagonist cytotoxicity were revealed from this combination therapy. Mechanisms of action assays were performed in order to investigate the main cell pathways induced by this treatment. Mitochondrial dysfunction generated a significant increase of reactive oxygen and nitrogen species production, causing severe cell injuries and promoting intense autophagy process and consequent apoptosis cell death. However, this phenomenon was not strong enough to promote dead in mammalian cell, providing the potential selective effect of the tested combination for the protozoa. Thus, the results confirmed that drugs involved in distinct metabolic routes are promising agents for drug combination therapy, promoting a synergistic effect.
Pharmacology, Toxicology and Pharmaceutical Science
7
9%
Chemistry
6
8%
Other
10
13%
Unknown
23
30%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 February 2017.
All research outputs
#18,530,362
of 22,952,268 outputs
Outputs from Frontiers in Microbiology
#19,427
of 24,986 outputs
Outputs of similar age
#237,840
of 310,755 outputs
Outputs of similar age from Frontiers in Microbiology
#368
of 448 outputs
Altmetric has tracked 22,952,268 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 24,986 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.3. This one is in the 9th percentile – i.e., 9% of its peers scored the same or lower than it.
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We're also able to compare this research output to 448 others from the same source and published within six weeks on either side of this one. This one is in the 8th percentile – i.e., 8% of its contemporaries scored the same or lower than it.
