Increased thiol levels in antimony-resistant Leishmania infantum isolated from treatment-refractory visceral leishmaniasis in Brazil

Magalhães, Lucas Sousa; Bomfim, Lays Gisele Santos; Mota, Sthefanne G; Cruz, Geydson Silveira da; Corrêa, Cristiane Bani; Tanajura, Diego Moura; Lipscomb, Michael W.; Borges, Valéria M.; Jesus, Amélia Ribeiro de; Almeida, Roque Pacheco de; Moura, Tatiana Rodrigues de

doi:10.1590/0074-02760170289

Cited by 12 publications

(2 citation statements)

References 31 publications

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“…The ability of NAC in killing L. infantum parasites was tested using a dose–response curve, as previously published ( Magalhães et al., 2018 ). Briefly, mid-log phase promastigotes of L. infantum isolate used in the experiments were washed (described above) and exposed to crescent concentrations of NAC (0.1 to 80 mM) in Schneider Insect’s Medium for 48 h. Parasites’ viability was determined by counting motile promastigotes in a Neubauer chamber.…”

Section: Methodsmentioning

confidence: 99%

Use of N-acetylcysteine as treatment adjuvant regulates immune response in visceral leishmaniasis: Pilot clinical trial and in vitro experiments

Magalhães

Melo²,

Damascena³

et al. 2022

Front. Cell. Infect. Microbiol.

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This investigation aimed to assess the effect of N-acetylcysteine (NAC) as an adjuvant treatment to alleviate visceral leishmaniasis (VL). The present work includes both blinded randomized clinical intervention and experimental in vitro studies. The clinical trial included 60 patients with VL randomly allocated into two groups: a test group (n = 30) treated with meglumine antimoniate plus NAC (SbV + NAC) and a control group (n = 30) treated with meglumine antimoniate only (SbV). The primary outcome was clinical cure (absence of fever, spleen and liver sizes reduction, and hematological improvement) in 180 days. The cure rate did not differ between the groups; both groups had similar results in all readout indices. The immunological parameters of the patients treated with SbV + NAC showed higher sCD40L in sera during treatment, and the levels of sCD40L were negatively correlated with Interleukin-10 (IL-10) serum levels. In addition, data estimation showed a negative correlation between the sCD40L levels and the spleen size in patients with VL. For the in vitro experiments, peripheral blood mononuclear cells (PBMCs) or PBMC-derived macrophages from healthy donors were exposed to soluble Leishmania antigen (SLA) or infected with stationary promastigotes of Leishmania infantum in the presence or absence of NAC. Results revealed that NAC treatment of SLA-stimulated PBMCs reduces the frequency of monocytes producing IL-10 and lowers the frequency of CD4+ and CD8+ T cells expressing (pro-)inflammatory cytokines. Together, these results suggest that NAC treatment may modulate the immune response in patients with VL, thus warranting additional investigations to support its case use as an adjuvant to antimony therapy for VL.

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Section: Methodsmentioning

confidence: 99%

Use of N-acetylcysteine as treatment adjuvant regulates immune response in visceral leishmaniasis: Pilot clinical trial and in vitro experiments

Magalhães

Melo²,

Damascena³

et al. 2022

Front. Cell. Infect. Microbiol.

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“…In another study, genomic analysis of L. infantum strains evidenced an association between deletion or mutations in LiMT and LiRos3 genes and miltefosine-resistance (Mondelaers et al, 2016). Finally, the increase of thiol levels was associated to antimony-resistance indicating that the redox metabolism has a role in the antimony-resistance of new world VL isolates (Magalhães et al, 2018).…”

Section: How Parasite Promotes Survival In a Non-friendly Environment?mentioning

confidence: 99%

Leishmania Spp-Host Interaction: There Is Always an Onset, but Is There an End?

Conceição-Silva

Morgado

2019

Front. Cell. Infect. Microbiol.

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For a long time Leishmaniasis had been considered as a neglected tropical disease. Recently, it has become a priority in public health all over the world for different aspects such as geographic spread, number of population living at risk of infection as well as the potential lethality and/or the development of disfiguring lesions in the, respectively, visceral and tegumentary forms of the disease. As a result, several groups have been bending over this issue and many valuable data have been published. Nevertheless, parasite-host interactions are still not fully known and, consequently, we do not entirely understand the infection dynamics and parasite persistence. This knowledge may point targets for modulation or blockage, being very useful in the development of measures to interfere in the course of infection/ disease and to minimize the risks and morbidity. In the present review we will discuss some aspects of the Leishmania spp—mammalian host interaction in the onset of infection and after the clinical cure of the lesions. We will also examine the information already available concerning the parasite strategy to evade immune response mainly at the beginning of the infection, as well as during the parasite persistence. This knowledge can improve the conditions of treatment, follow-up and cure control of patients, minimizing the potential damages this protozoosis can cause to infected individuals.

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Oxidative Stress and Antioxidants in Host Defense in Leishmaniasis

Ferrari

2019

Oxidative Stress in Microbial Diseases

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Increased thiol levels in antimony-resistant Leishmania infantum isolated from treatment-refractory visceral leishmaniasis in Brazil

Cited by 12 publications

References 31 publications

Use of N-acetylcysteine as treatment adjuvant regulates immune response in visceral leishmaniasis: Pilot clinical trial and in vitro experiments

Use of N-acetylcysteine as treatment adjuvant regulates immune response in visceral leishmaniasis: Pilot clinical trial and in vitro experiments

Leishmania Spp-Host Interaction: There Is Always an Onset, but Is There an End?

Oxidative Stress and Antioxidants in Host Defense in Leishmaniasis

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