ArticlePloS one2010
DETC induces Leishmania parasite killing in human in vitro and murine in vivo models: a promising therapeutic alternative in Leishmaniasis.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Randomized Study About Influence of Food on the Pharmacokinetics of Disulfiram Metabolites in Healthy Individuals.European journal of drug metabolism and pharmacokinetics · 2026Trial
- Cathepsin G and neutrophil elastase control Leishmania infantum parasitism through TLRs-dependent induction of IFN-α and TNF-α.Communications biology · 2026Article
- Synthesis of 1,2,3-Triazole-Containing Methoxylated Cinnamides and Their Antileishmanial Activity against thePharmaceuticals (Basel, Switzerland) · 2023Article
- Roles of Oxidative Stress and Nrf2 Signaling in Pathogenic and Non-Pathogenic Cells: A Possible General Mechanism of Resistance to Therapy.Antioxidants (Basel, Switzerland) · 2023Review
- Quantum Biochemistry Screening and In Vitro Evaluation ofInternational journal of molecular sciences · 2022Article
- Long-term hematopoietic stem cells as a parasite niche during treatment failure in visceral leishmaniasis.Communications biology · 2022Article
- In Vitro Validation of Antiparasitic Activity of PLA-Nanoparticles of Sodium Diethyldithiocarbamate againstPharmaceutics · 2022Article
- The combination of diethyldithiocarbamate and copper ions is active againstFrontiers in microbiology · 2022Article
- Lipid droplets of protozoan parasites: survival and pathogenicity.Memorias do Instituto Oswaldo Cruz · 2022Article
- Effects of negative air ions (NAIs) on Leishmania major: A novel tool for treatment of zoonotic cutaneous leishmaniasis (ZCL).PloS one · 2022Article
- The repositioned drugs disulfiram/diethyldithiocarbamate combined to benznidazole: Searching for Chagas disease selective therapy, preventing toxicity and drug resistance.Frontiers in cellular and infection microbiology · 2022Article
- Antimony resistance associated with persistence of Leishmania (Leishmania) infantum infection in macrophages.Parasitology research · 2021Article
- Insights of antiparasitic activity of sodium diethyldithiocarbamate against different strains of Trypanosoma cruzi.Scientific reports · 2021Article
- Review
- Transcription Factors Interplay Orchestrates the Immune-Metabolic Response ofFrontiers in cellular and infection microbiology · 2021Review
- Evaluation of in vitro and in vivo Efficacy of a Novel Amphotericin B-Loaded Nanostructured Lipid Carrier in the Treatment ofInternational journal of nanomedicine · 2020Article
- Application of Dithiocarbamates as Potential New Antitrypanosomatids-Drugs: Approach Chemistry, Functional and Biological.Molecules (Basel, Switzerland) · 2019Review
- The Paradoxical Leishmanicidal Effects of Superoxide Dismutase (SOD)-Mimetic Tempol inFrontiers in cellular and infection microbiology · 2019Article
- The Potential Role of Nrf2 Signaling in Leishmania Infection Outcomes.Frontiers in cellular and infection microbiology · 2019Review
- Systems Approach Reveals Nuclear Factor Erythroid 2-Related Factor 2/Protein Kinase R Crosstalk in Human Cutaneous Leishmaniasis.Frontiers in immunology · 2017Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChemotherapy remains the primary tool for treatment and control of human leishmaniasis. However, currently available drugs present serious problems regarding side-effects, variable efficacy, and cost. Affordable and less toxic drugs are urgently needed for leishmaniasis. METHODOLOGY/PRINCIPAL
findingsWe demonstrate, by microscopy and viability assays, that superoxide dismutase inhibitor diethyldithiocarbamate (DETC) dose-dependently induces parasite killing (p<0.001) and is able to "sterilize" Leishmania amazonensis infection at 2 mM in human macrophages in vitro. We also show that DETC-induced superoxide production (p<0.001) and parasite destruction (p<0.05) were reverted by the addition of the antioxidant N-acetylcysteine, indicating that DETC-induced killing occurs through oxidative damage. Furthermore, ultrastructural analysis by electron microscopy demonstrates a rapid and highly selective destruction of amastigotes in the phagosome upon DETC treatment, without any apparent damage to the host cell, including its mitochondria. In addition, DETC significantly induced parasite killing in Leishmania promastigotes in axenic culture. In murine macrophages infected with Leishmania braziliensis, DETC significantly induced in vitro superoxide production (p = 0.0049) and parasite killing (p = 0.0043). In vivo treatment with DETC in BALB/C mice infected with Leishmania braziliensis caused a significant decrease in lesion size (p<0.0001), paralleled by a 100-fold decrease (p = 0.0087) in parasite burden. CONCLUSIONS/SIGNIFICANCE: Due to its strong leishmanicidal effect in human macrophages in vitro, its in vivo effectiveness in a murine model, and its previously demonstrated in vivo safety profile in HIV treatment, DETC treatment might be considered as a valuable therapeutic option in human leishmaniasis, including HIV/Leishmania co-infection.
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