Evidence map›Paper›PMID 30694414›Full record

ArticleParasitology research2019

The antidepressant clomipramine induces programmed cell death in Leishmania amazonensis through a mitochondrial pathway.

Jean Henrique da Silva Rodrigues, Nathielle Miranda, Hélito Volpato, Tânia Ueda-Nakamura, Celso Vataru Nakamura

Abstract read
PubMed Publisher
In one paragraph

Article in Parasitology research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.1field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 27 citations in OpenAlex.

  1. Cell Death and Unprecedent Cytoskeletal Changes inChemical & biomedical imaging · 2026
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  3. In Vitro Assessment of the Combined Activity of Amphotericin B and CuTropical medicine and infectious disease · 2025
    Article
  4. Article
  5. Article
  6. Review
  7. Analysis of the anti-Candida activity of tricyclic antidepressants in association with amphotericin B and their antifungal mechanisms.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2024
    Article
  8. EXCLI journal · 2024
    Article
  9. Article
  10. InhibitingPharmaceuticals (Basel, Switzerland) · 2023
    Article
  11. Article
  12. Article
  13. Homology Modeling,Frontiers in cellular and infection microbiology · 2022
    Article
  14. GC-MS screening and antiparasitic action ofJournal of parasitic diseases : official organ of the Indian Society for Parasitology · 2021
    Article
  15. Article
  16. Article
  17. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Jean Henrique da Silva RodriguesPrograma de Pós-Graduação em Ciências Biológicas, Área de Concentração Biologia Celular e Molecular, Universidade Estadual de Maringá, Maringá, Paraná, Brazil.
Nathielle MirandaPrograma de Pós-Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, Paraná, Brazil.
Hélito VolpatoPrograma de Pós-Graduação em Ciências Biológicas, Área de Concentração Biologia Celular e Molecular, Universidade Estadual de Maringá, Maringá, Paraná, Brazil.
Tânia Ueda-NakamuraPrograma de Pós-Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, Paraná, Brazil.
Celso Vataru NakamuraPrograma de Pós-Graduação em Ciências Biológicas, Área de Concentração Biologia Celular e Molecular, Universidade Estadual de Maringá, Maringá, Paraná, Brazil. cvnakamura@uem.br.ORCID http://orcid.org/0000-0003-2902-4578
Universidade Estadual de Maringá · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite many efforts, the currently available treatments for leishmaniasis are not fully effective. To discover new medications, drug repurposing arises as a promising strategy. We present data that supports the use of the antidepressant clomipramine against Leishmania amazonensis. The drug presented selective activity at micromolar range against both the parasite forms and stimulated nitric oxide production in host macrophages. Regarding the mechanism of action, clomipramine led parasites do mitochondrial depolarization, which coupled with the inhibition of trypanothione reductase induced strong oxidative stress in the parasites. The effects observed in promastigotes included lipoperoxidation, plasma membrane permeabilization, and apoptosis hallmarks (i.e., DNA fragmentation, phosphatidylserine exposure, and cell shrinkage). The mechanism of action in both parasitic forms was quite similar, but amastigotes also exhibited energetic stress, reflected by a reduction of adenosine triphosphate levels. Such differential effects might be attributable to the metabolic particularities of each form of the parasitic. Ultrastructural alterations of the endomembrane system and autophagy were also observed, possibly indicating an adaptive response to oxidative stress. Our results suggest that clomipramine interferes with the redox metabolism of L. amazonensis. In spite of the cellular responses to recover the cellular homeostasis, parasites underwent programmed cell death.

Indexed as

AnimalsAntidepressive Agents, TricyclicAntiprotozoal AgentsApoptosisCell LineClomipramineLeishmaniaMacrophagesMiceMitochondriaAntidepressive Agents, TricyclicAntiprotozoal AgentsClomipramineApoptosisIntracellular amastigotes isolationLeishmaniasisOxidative stressRepositioningRepurposing

Identifiers

PMID30694414
OpenAlexW2914664753

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.