Combination Therapy with Tamoxifen and Amphotericin B in Experimental Cutaneous Leishmaniasis

Trinconi, Cristiana T.; Reimão, Juliana Quero; Yokoyama-Yasunaka, Jenicer K.U.; Miguel, Danilo C.; Uliana, Sílvia Reni Bortolin

doi:10.1128/aac.01315-13

Cited by 64 publications

(53 citation statements)

References 35 publications

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“…Advantages of a combination treatment include increased efficacy, less drug resistance, lower drug dosage and a general decrease in side effects50. Combination therapy can also hinder the appearance of monotherapy-resistant parasites51 and, as such, it is being pursued in recent studies using Tamoxifen as an alternative to treat CL5253. Herein, topical BC-DETC was as effective as intraperitioneal Sb v when we evaluated lesion development and parasite replication at the infection site.…”

Section: Discussionmentioning

confidence: 98%

DETC-based bacterial cellulose bio-curatives for topical treatment of cutaneous leishmaniasis

Celes

Trovatti

Khouri

et al. 2016

Sci Rep

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The treatment of leishmaniasis still relies on drugs with potentially serious adverse effects. Herein, we tested a topical formulation of bacterial cellulose (BC) membranes containing Diethyldithiocarbamate (DETC), a superoxide dismutase 1 inhibitor. Leishmania-infected macrophages exposed to BC-DETC resulted in parasite killing, without pronounced toxic effects to host cells. This outcome was associated with lower SOD1 activity and higher production of superoxide and cytokine mediators. Topical application of BC-DETC significantly decreased lesion size, parasite load and the inflammatory response at the infection site, as well as the production of both IFN-γ and TNF. Combination of topical BC-DETC plus intraperitoneal Sbv also significantly reduced disease development and parasite load. The leishmanicidal effect of BC-DETC was extended to human macrophages infected with L. braziliensis, highlighting the feasibility of BC-DETC as a topical formulation for chemotherapy of cutaneous leishmaniasis caused by L. braziliensis.

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Section: Discussionmentioning

confidence: 98%

DETC-based bacterial cellulose bio-curatives for topical treatment of cutaneous leishmaniasis

Celes

Trovatti

Khouri

et al. 2016

Sci Rep

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“…In parasites, it induces cell death by apoptosis and, in infected macrophages, modifies the alkaline intravacuolar pH and increases drug action against amastigote forms (93)(94)(95)(96)(97)(98). The combination of tamoxifen with reference drugs (amphotericin B or miltefosine) used in the treatment of leishmaniasis has also shown promising results (99,100). Raloxifene, an estrogen receptor modulating drug, was tested against the promastigotes of L. amazonensis, L.…”

Section: Anticancer Drugsmentioning

confidence: 99%

Leishmaniasis treatment update of possibilities for drug repurposing

Torres-Santos¹

2018

Front Biosci

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The leishmaniases represent a public health problem in under-developed countries and are considered a neglected disease by the World Health Organization (WHO). They are cuased by parasites with different clinical manifestations. Currently, there is no vaccine, and treatment is in-efficient and is associated with both serious side effects often leading to resistance to the parasites. Thus, it is essential to search for new treatment strategies, such as drug repurposing, i.e., the use of drugs that are already used for other diseases. The discovery of new clinical applications for approved drugs is strategic for lowering the cost of drug discovery since human toxicity assays are already conducted. Here, we review a broad analysis of the different aspects of this approach for anti-leishmanial treatment.

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“…Recently, tamoxifen, an antineoplastic agent for the prophylactic treatment of malignancies was tested against cutaneous leishmaniasis with promising results [10,11]. …”

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confidence: 99%

Evaluation of Boldine Activity against Intracellular Amastigotes of Leishmania amazonensis

2017

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Leishmaniasis is a neglected and endemic disease that affects poorest population mainly in developing countries. A lack of adequate and definitive chemotherapeutic agents to fight against this infection has led to the investigation of numerous compounds. The aim of this study was to investigate in vitro activity of boldine against Leishmania amazonensis murine cell infection. Boldine ((S)-2,9-dihydroxy-1,10-dimethoxy-aporphine) is an aporphine alkaloid found abundantly in the leaves/bark of boldo (Peumus boldus Molina), a widely distributed tree native to Chile. The in vitro system consisted of murine macrophage infection with amastigotes of L. amazonensis treated with different concentrations from 50 to 600 μg/ml of boldine for 24 hr. Intracellular parasite destruction was assessed by morphological examination and boldine cytotoxicity to macrophages was tested by the MTT viability assay. When cells were treated with 100 μg/ml of boldine the reduction of parasite infection was 81% compared with untreated cultures cells. Interestingly, boldine-treatment caused a concentration-dependent decrease of macrophage infection that culminated with 96% of reduction when cells were submitted to 600 μg/ml of boldine. Cell cultures exposed to 100 μg/ml of boldine and 300 μg/ml of Glucantime® during 24 hr showed a significant reduction of 50% in parasitized cells compared with cell cultures exposed just to Glucantime®. The study showed that treatment with boldine produces a better effect than treatment with the reference antimonial drug, glucantime, in L. amazonensis infected macrophage. Our results suggest that boldine is a potentially useful agent for the treatment of leishmaniasis.

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Combination Therapy with Tamoxifen and Amphotericin B in Experimental Cutaneous Leishmaniasis

Cited by 64 publications

References 35 publications

DETC-based bacterial cellulose bio-curatives for topical treatment of cutaneous leishmaniasis

DETC-based bacterial cellulose bio-curatives for topical treatment of cutaneous leishmaniasis

Leishmaniasis treatment update of possibilities for drug repurposing

Evaluation of Boldine Activity against Intracellular Amastigotes of Leishmania amazonensis

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