<i>Leishmania amazonensis</i> trypanothione reductase: Evaluation of the effect of glutathione analogs on parasite growth, infectivity and enzyme activity

Castro‐Pinto, Denise Barçante; Lima, Edson L. S.; Cunha, Andréa Sousa da; Genestra, Marcelo; Léo, Rosa M. de; Monteiro, Fabiane Pereira; Leon, Leonor L.

doi:10.1080/14756360600920180

Cited by 16 publications

(9 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In L. amazonensis, reduced glutathione (GSH) is a component of trypanothione, a major antioxidant of this parasite, 21 and intracellular GSH levels can be increased by treatment with the antioxidant N-acetyl-L-cysteine (NAC). 22 To confirm that the inhibitory effects of 1 are mediated by ROS production, L. amazonensis promastigotes were preincubated with GSH or NAC (300 μM).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Effect of Apigenin on Leishmania amazonensis Is Associated with Reactive Oxygen Species Production Followed by Mitochondrial Dysfunction

et al. 2015

View full text Add to dashboard Cite

Leishmaniasis is an important neglected disease caused by protozoa of the genus Leishmania that affects more than 12 million people worldwide. Leishmaniasis treatment requires the administration of toxic and poorly tolerated drugs, and parasite resistance greatly reduces the efficacy of conventional medications. Apigenin (1), a naturally occurring plant flavone, has a wide range of reported biological effects. In this study, antileishmanial activity of 1 in vitro was investigated, and its mechanism of action against Leishmania amazonensis promastigotes was described. Treatment with 1 for 24 h resulted in concentration-dependent inhibition of cellular proliferation (IC50 = 23.7 μM) and increased reactive oxygen species (ROS) generation. Glutathione and N-acetyl-l-cysteine protected L. amazonensis from the effects of 1 and reduced ROS levels after the treatment. By contrast, oxidized glutathione did not reduce the levels of ROS caused by 1 by not preventing the proliferation inhibition. Apigenin 1 also induced an extensive swelling in parasite mitochondria, leading to an alteration of the mitochondrial membrane potential, rupture of the trans-Golgi network, and cytoplasmic vacuolization. These results demonstrate the leishmanicidal effect of 1 and suggest the involvement of ROS leading to mitochondrial collapse as part of the mechanism of action.

show abstract

Section: ■ Results and Discussionmentioning

confidence: 99%

Effect of Apigenin on Leishmania amazonensis Is Associated with Reactive Oxygen Species Production Followed by Mitochondrial Dysfunction

et al. 2015

View full text Add to dashboard Cite

show abstract

“…It has been suggested that to sustain active infections within macrophages, parasites should preserve a detectable expression of trypanothione reductase (TR) (Castro-Pinto et al, 2007) and a high level of nitric oxide (NO) production (Genestra et al, 2006). TR and NO help parasites to maintain infection by neutralizing toxic free radicals (nitrogenated and oxygenated) produced by host cells.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies from our group have already shown that noninfective parasites have a low expression of TR, as well as low production of NO. These data could explain why parasites with no detectable metacyclic forms were unable to sustain the in vitro and in vivo infections (Genestra et al, 2006;Castro-Pinto et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Differences in the Antigenic Profile and Infectivity of Murine Macrophages of Leishmania (Viannia) Parasites

Matta¹,

Cysne-Finkelstein²,

Machado³

et al. 2010

Journal of Parasitology

View full text Add to dashboard Cite

The antigenic profile and infectivity were compared between 3 recent Leishmania (Viannia) isolates from the Amazonian region (Instituto Nacional de Pesquisas da Amazonia [INPA] strains) and 3 World Health Organization (WHO) reference species (Leishmania guyanensis, Leishmania braziliensis, and Leishmania naiffi). Differences were observed in the peak and extent of promastigote growth. The WHO reference strains exhibited significantly higher exponential growth as promastigotes than INPA strains. In the immunoblot analyses, the INPA strains revealed several specific peptide fragments, as well as the greatest recognition frequencies by sera from Leishmania sp.-infected patients; among the latter, antigens derived from L. naiffi were the most frequently recognized. In vitro infection was carried out using mice peritoneal macrophages; all strains were able to enter the macrophages, but only L. amazonensis was able to reproduce. A striking observation was that L. naiffi exhibited the longest survival time inside the macrophages. Our data strongly suggest the application of recently isolated parasites as sources of antigen for diagnosis procedures. Moreover, L. naiffi species possesses several characteristics relevant for its use as a source of novel antigens to be explored in the design of diagnostic tools and vaccines.

show abstract

“…In Trypanosomes and Leishmanias, trypanothione plays a central role in parasite protection against mammalian host defence systems by recycling trypanothione disulfide by the enzyme trypanothione reductase (TR). 60 Although Kinetoplastida parasites lack GSH reductase, they maintain significant levels of GSH. We also verified the higher resistance of axenic amastigotes to SNP (Figure 3) than promastigotes, corroborating with recent results of our Laboratory, that showed higher TR activity in axenic amastigotes than in promastigotes.…”

Section: Discussionmentioning

confidence: 99%

In vitro sodium nitroprusside‐mediated toxicity towards Leishmania amazonensis promastigotes and axenic amastigotes

Genestra

Soares‐Bezerra

Gomes‐Silva

et al. 2008

Cell Biochemistry & Function

Self Cite

View full text Add to dashboard Cite

Leishmania parasites survive despite exposure to the toxic nitrosative oxidants during phagocytosis by the host cell. In this work, the authors investigated comparatively the resistance of Leishmania amazonensis promastigotes and axenic amastigotes to a relatively strong nitrosating agent that acts as a nitric oxide (NO) donor, sodium nitroprusside (SNP). Results demonstrate that SNP is able to decrease, in vitro, the number of L. amazonensis promastigotes and axenic amastigotes in a dose-dependent maner. Promastigotes, cultured in the presence of 0.25, 0.5, and 1 mmol L(-1) SNP for 24 h showed about 75% growth inhibition, and 97-100% when the cultures were treated with >2 mmol L(-1) SNP. In contrast, when axenic amastigotes were growing in the presence of 0.25-8 mM SNP added to the culture medium, 50% was the maximum of growth inhibition observed. Treated promastigotes presented reduced motility and became round in shape further confirming the leishmanicidal activity of SNP. On the other hand, axenic amastigotes, besides being much more resistant to SNP-mediated cytotoxicity, did not show marked morphological alteration when incubated for 24 h, until 8 mM concentrations of this nitrosating agent were used. The cytotoxicity toward L. amazonensis was attenuated by reduced glutathione (GSH), supporting the view that SNP-mediated toxicity triggered multiple oxidative mechanisms, including oxidation of thiols groups and metal-independent oxidation of biomolecules to free radical intermediates.

show abstract

Leishmania amazonensis trypanothione reductase: Evaluation of the effect of glutathione analogs on parasite growth, infectivity and enzyme activity

Cited by 16 publications

References 18 publications

Effect of Apigenin on Leishmania amazonensis Is Associated with Reactive Oxygen Species Production Followed by Mitochondrial Dysfunction

Effect of Apigenin on Leishmania amazonensis Is Associated with Reactive Oxygen Species Production Followed by Mitochondrial Dysfunction

Differences in the Antigenic Profile and Infectivity of Murine Macrophages of Leishmania (Viannia) Parasites

In vitro sodium nitroprusside‐mediated toxicity towards Leishmania amazonensis promastigotes and axenic amastigotes

Contact Info

Product

Resources

About