Melittin induces in vitro death of Leishmania (Leishmania) infantum by triggering the cellular innate immune response

Pereira, Andréia Vieira; Barros, Gustavo; Pinto, Érika G.; Tempone, André G.; Orsi, Ricardo de Oliveira; Santos, Lucilene Delazari dos; Calvi, Sueli Aparecida; Ferreira, Rui Seabra; Pimenta, Daniel C.; Barraviera, Benedito

doi:10.1186/s40409-016-0055-x

Cited by 34 publications

(31 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The two major reactive species in macrophages are superoxide (O 2 − ) and nitric oxide (NO) [37,38]. It is observed that if drugs have ideal anti-parasitic effects, the NO and H 2 O 2 productions of leishmania-infected macrophages decrease [4,39]. In our research, elevated levels of NO and H 2 O 2 were found in leishmaniainfected macrophages and a strong inhibition of NO and H 2 O 2 metabolites was observed upon treatment with DHCsA-d or SSG.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of in vitro antileishmanial efficacy of cyclosporin A and its non-immunosuppressive derivative, dihydrocyclosporin A

Zheng

Chen

et al. 2020

Parasites Vectors

View full text Add to dashboard Cite

Background: New therapeutic drugs are urgently needed against visceral leishmaniasis because current drugs, such as pentavalent antimonials and miltefosine, produce severe side effects and development of resistance. Whether cyclosporine A (CsA) and its derivatives can be used as therapeutic drugs for visceral leishmaniasis has been controversial for many years. Methods:In this study, we evaluated the efficacy of CsA and its derivative, dihydrocyclosporin A (DHCsA-d), against promastigotes and intracellular amastigotes of Leishmania donovani. Sodium stibogluconate (SSG) was used as a positive control. Results:Our results showed that DHCsA-d was able to inhibit the proliferation of L. donovani promastigotes (IC 50 : 21.24 μM and 12.14 μM at 24 h and 48 h, respectively) and intracellular amastigotes (IC 50 : 5.23 μM and 4.84 μM at 24 and 48 h, respectively) in vitro, but CsA treatment increased the number of amastigotes in host cells. Both DHCsA-d and CsA caused several alterations in the morphology and ultrastructure of L. donovani, especially in the mitochondria. However, DHCsA-d showed high cytotoxicity towards cells of the mouse macrophage cell line RAW264.7, with CC50 values of 7.98 μM (24 h) and 6.65 μM (48 h). Moreover, DHCsA-d could increase IL-12, TNF-α and IFN-γ production and decrease the levels of IL-10, IL-4, NO and H 2 O 2 in infected macrophages. On the contrary, CsA decreased IL-12, TNF-α, and IFN-γ production and increased the levels of IL-10, IL-4, NO and H 2 O 2 in infected macrophages. The expression of L. donovani cyclophilin A (LdCyPA) in promastigotes and intracellular amastigotes and the expression of cyclophilin A (CyPA) in RAW 264.7 cells were found to be significantly downregulated in the CsA-treated group compared to those in the untreated group. However, no significant changes in LdCyPA and CyPA levels were found after DHCsA-d or SSG treatment. Conclusions:Our findings initially resolved the dispute regarding the efficacy of CsA and DHCsA-d for visceral leishmaniasis treatment. CsA showed no significant inhibitory effect on intracellular amastigotes. DHCsA-d significantly inhibited promastigotes and intracellular amastigotes, but it was highly cytotoxic. Therefore, CsA and DHCsA-d are not recommended as antileishmanial drugs.

show abstract

Section: Discussionmentioning

confidence: 99%

Evaluation of in vitro antileishmanial efficacy of cyclosporin A and its non-immunosuppressive derivative, dihydrocyclosporin A

Zheng

Chen

et al. 2020

Parasites Vectors

View full text Add to dashboard Cite

show abstract

“…In fact, melittin from Apis mellifera acted in vitro against promastigotes and intracellular amastigotes of Leishmania infantum. The results suggested that melittin can indirectly eliminate the parasite through a macrophage immunomodulatory effect [61]. Bee venom is also known to exhibit antifungal activities.…”

Section: Antimicrobial Agents From Wasps and Beesmentioning

confidence: 99%

Antimicrobials from Venomous Animals: An Overview

et al. 2020

View full text Add to dashboard Cite

The inappropriate or excessive use of antimicrobial agents caused an emerging public health problem due to the resulting resistance developed by microbes. Therefore, there is an urgent need to develop effective antimicrobial strategies relying on natural agents with different mechanisms of action. Nature has been known to offer many bioactive compounds, in the form of animal venoms, algae, and plant extracts that were used for decades in traditional medicine. Animal venoms and secretions have been deeply studied for their wealth in pharmaceutically promising molecules. As such, they were reported to exhibit many biological activities of interest, such as antibacterial, antiviral, anticancer, and anti-inflammatory activities. In this review, we summarize recent findings on the antimicrobial activities of crude animal venoms/secretions, and describe the peptides that are responsible of these activities.

show abstract

“…Even as singular or a hybrid peptide, it was studied against Leishmania spp. and Trypanosoma spp., and researchers found direct antimicrobial and indirect immunomodulatory results [27][28][29][30].Another promising result was found about HIV. Dosedependently, melittin was found to prevent synthesis of group-specific antigen (gag)/DNA polymerase (pol) and intracellularly reduce Gag antigen and HIV-1 mRNA levels.…”

Section: Major Bioactive Substancesmentioning

confidence: 99%

Bee venom: A medical perspective

Sığ

Güney

Sig

et al. 2019

Turkish Journal of Clinics and Laboratory

View full text Add to dashboard Cite

Apitherapy is a complementary medical technique that has an old history and is applied in various diseases worldwide. Apitherapeutical applications are not treatment methods by themself, but they can be substantial parts of multidisciplinary approaches. One of them, bee venom therapy (BVT), is a currently-applied method worldwide. Bee venom (BV) includes several substances such as peptides, phospholipids, bioactive amines, amino acids, sugars, pheromones, enzymes and minerals.Studies on whole BV and its singular components indicated that they have a huge potential in anti-inflammatory, anti-arthritis, anti-nociceptive, neuroprotective, anti-tumoral, anti-microbial, anti-diabetic and anti-rheumatic activities. Results of in vivo studies against arthritis, Parkinson's and Alzheimer's disease and cancer are very promising, and also in vitro results indicating other activities such as antimicrobial effect are observed. Although mechanisms of action and many bioactive substances still remain unclear, beneficial effects and potential utilities in certain medical conditions are obvious. It seems bioactive components of BV may open new doors in treatment of various diseases.

show abstract

Melittin induces in vitro death of Leishmania (Leishmania) infantum by triggering the cellular innate immune response

Cited by 34 publications

References 46 publications

Evaluation of in vitro antileishmanial efficacy of cyclosporin A and its non-immunosuppressive derivative, dihydrocyclosporin A

Evaluation of in vitro antileishmanial efficacy of cyclosporin A and its non-immunosuppressive derivative, dihydrocyclosporin A

Antimicrobials from Venomous Animals: An Overview

Bee venom: A medical perspective

Contact Info

Product

Resources

About