Efficacy of lapachol on treatment of cutaneous and visceral leishmaniasis

Araújo, Iasmin Aparecida Cunha; Paula, Renata Cristina de; Alves, Ceres Luciana; Faria, Karen Ferraz; Oliveira, Marco Miguel de; Mendes, Gabriela Gonçalves; Dias, Eliane Martins Ferreira Abdias; Ribeiro, Raul Rio; Oliveira, Alaı́de Braga de; Silva, Sydnei Magno da

doi:10.1016/j.exppara.2019.02.013

Cited by 33 publications

(12 citation statements)

References 47 publications

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“…UA was solubilized in DMSO and further PBS (never exceeding 1% DMSO); and AmB was solubilized in sterile water. The highest doses of 1.0 and 5.0 mg/kg from AmB and UA, respectively, were selected based on previously published works [ 21 , 45 , 46 ].…”

Section: Methodsmentioning

confidence: 99%

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Ursolic Acid Potentializes Conventional Therapy in Experimental Leishmaniasis

et al. 2020

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Ursolic acid (UA) is a triterpene with a broad array of pharmacological activities. In leishmaniasis, UA killed different species of parasites, and it was active in the experimental model of cutaneous and visceral leishmaniasis. Thus, the objective of this work was to study the therapeutic efficacy of the conventional drugs amphotericin B (AmB) or glucantime (Glu) combined with UA in experimental visceral and cutaneous leishmaniasis, respectively. L. (L.) infantum-infected hamsters were treated with AmB alone or combined with UA. L. (L.) amazonensis-infected BALB/c mice were treated with Glu alone or combined with UA. Animals were treated for 15 consecutive days by intraperitoneal or intralesional routes. Following one week after the last dose, the tissue parasitism and cellular immune responses were analyzed. Hamsters treated with 0.2 and 1.0 mg/kg of AmB plus 1.0 mg/kg of UA showed low hepatic and splenic parasitisms; however, AmB given as monotherapy did not reduce the number of viable parasites in the spleen of treated animals. In cutaneous leishmaniasis, Glu given as monotherapy was inactive at 2.0 mg/kg, showed mild activity at 10.0 mg/kg, and at 50.0 mg/kg was highly active at eliminating parasites in the skin. When animals were treated with Glu plus UA, higher leishmanicidal activity was observed in comparison to all groups treated with monotherapy schemes, and such activity was related to lesion improvement and upregulation of IFN-γ production. Altogether, data suggest that the association of drugs for the treatment of leishmaniasis can increase the efficiency of the treatment and decrease the toxicity associated to the conventional drugs.

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Section: Methodsmentioning

confidence: 99%

“…Forty BALB/c mice (four weeks old; weight ~ 25 g) were inoculated at the base of the tail with 2 × 10 7 promastigote forms of L. amazonensis in stationary phase of growth (final volume 25 µL) as described in previous published works [ 9 , 46 , 47 , 48 , 49 ]. Five healthy control group was injected only with physiological solution.…”

Section: Methodsmentioning

confidence: 99%

Ursolic Acid Potentializes Conventional Therapy in Experimental Leishmaniasis

et al. 2020

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“…Some products of natural origin showed not very encouraging results. Lapachol showed promising in vitro antileishmanial activity against the promastigote forms and intracellular amastigote forms of L. infantum (IC 50 135.79 and 171.26 μM, respectively), with a high selectivity index (Araújo et al, 2019). However, in murine VL models, oral treatment with lapachol (25 mg/kg/day) reduced the hepatic parasitic load and splenic lesions by 4.6 and 5.3 times, respectively.…”

Section: Resultsmentioning

confidence: 99%

Recent strategies for the development of oral medicines for the treatment of visceral leishmaniasis

Souza

Costa

Silva

et al. 2020

Drug Development Research

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Considered prevalent in many countries on five continents, especially in low‐income regions, leishmaniasis is a neglected tropical disease classified by World Health Organization as one of the diseases for which the development of new treatments is a priority. It is an infectious disease caused by protozoa of the genus Leishmania, whose species may cause different clinical manifestations, such as cutaneous and visceral leishmaniasis (VL). Treatment is exclusively by drug therapy, as it has not been possible to develop vaccines yet. Currently available drugs are not fully effective in all cases; they have parenteral administration and exhibit a number of serious and very common adverse effects. The only oral drug available is expensive and it is not available in many endemic countries. Injectable administration is the main problem of treatments, since it requires patients to go to health centers, hospitalization and professional administration, which are conditions that are not adapted to the reality of the poverty conditions of patients with the disease. In this context, the development of an oral medicine has become a focus as it may solve many of these issues. Based on this scenario, this review aimed to investigate which therapeutic alternatives have been studied for the development of oral drugs directed to the treatment of human VL.

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“…Interest in the use of natural products to treat diseases such as leishmaniasis has increased in recent decades. For instance, naphthoquinones and quinolines have been used in in vitro experiments against various Leishmania spp., and positive results have been obtained [2,7]. These compounds are natural aromatic metabolites found in several plant families, and they present relevant biological activity, such as antileishmanial action [37,46].…”

Section: Discussionmentioning

confidence: 99%

A clioquinol-containing Pluronic^® F127 polymeric micelle system is effective in the treatment of visceral leishmaniasis in a murine model

et al. 2020

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A clioquinol (ICHQ)-containing Pluronic® F127 polymeric micelle system (ICHQ/Mic) was recently shown to be effective against Leishmania amazonensis infection in a murine model. In the present study, ICHQ/Mic was tested against L. infantum infection. BALB/c mice (n = 12 per group) were infected with L. infantum stationary promastigotes through subcutaneous injection and, 45 days after challenge, received saline or were treated via the subcutaneous route with empty micelles, ICHQ or ICHQ/Mic. In addition, animals were treated with miltefosine by the oral route, as a drug control. Half of the animals were euthanized 1 and 15 days after treatment, aiming to evaluate two endpoints after therapy, when parasitological and immunological parameters were investigated. Results showed that the treatment using miltefosine, ICHQ or ICHQ/Mic induced significantly higher anti-parasite IFN-γ, IL-12, GM-CSF, nitrite and IgG2a isotype antibody levels, which were associated with low IL-4 and IL-10 production. In addition, a higher frequency of IFN-γ and TNF-α-producing CD4+ and CD8+ T-cells was found in these animals. The parasite load was evaluated in distinct organs, and results showed that the treatment using miltefosine, ICHQ or ICHQ/Mic induced significant reductions in organic parasitism in the treated and infected mice. A comparison between the treatments suggested that ICHQ/Mic was the most effective in inducing a highly polarized Th1-type response, as well as reducing the parasite load in significant levels in the treated and infected animals. Data obtained 15 days after treatment suggested maintenance of the immunological and parasitological responses. In conclusion, ICHQ/Mic could be considered in future studies for the treatment of visceral leishmaniasis.

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Efficacy of lapachol on treatment of cutaneous and visceral leishmaniasis

Cited by 33 publications

References 47 publications

Ursolic Acid Potentializes Conventional Therapy in Experimental Leishmaniasis

Ursolic Acid Potentializes Conventional Therapy in Experimental Leishmaniasis

Recent strategies for the development of oral medicines for the treatment of visceral leishmaniasis

A clioquinol-containing Pluronic^® F127 polymeric micelle system is effective in the treatment of visceral leishmaniasis in a murine model

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Efficacy of lapachol on treatment of cutaneous and visceral leishmaniasis

Cited by 33 publications

References 47 publications

Ursolic Acid Potentializes Conventional Therapy in Experimental Leishmaniasis

Ursolic Acid Potentializes Conventional Therapy in Experimental Leishmaniasis

Recent strategies for the development of oral medicines for the treatment of visceral leishmaniasis

A clioquinol-containing Pluronic® F127 polymeric micelle system is effective in the treatment of visceral leishmaniasis in a murine model

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Product

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A clioquinol-containing Pluronic^® F127 polymeric micelle system is effective in the treatment of visceral leishmaniasis in a murine model