Topical treatment of experimental cutaneous leishmaniasis in golden hamster (Mesocricetus auratus) with formulations containing pentamidine

Wyrepkowski, Cláudia Dantas Comandolli; Grafova, Iryna; Naiff, Maricleide de Farias; Avella, Maurizio; Gentile, Gennaro; Grafov, Andriy; Franco, Antônia Maria Ramos

doi:10.1590/1809-4392201601333

Cited by 3 publications

(3 citation statements)

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“…However, there was an increase, although lower than in the negative control and also in the group treated with Glucantime®, regarding the presence of parasites after 20 days without receiving treatment. Hamsters treated with a topical formulation with pentamidine also showed viable parasites after end of treatment (Comandolli-Wyrepkowski et al 2017).…”

Section: Discussionmentioning

confidence: 98%

Antileishmanial activity of extracts from Libidibia ferrea: development of in vitro and in vivo tests

et al. 2017

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Treatment of cutaneous leishmaniasis (CL) is difficult due to the scarce number of drugs able to eliminate completely the intracellular form of the parasite. In the present study, the aim was to evaluate: i) phytochemical properties of extracts from Libidibia ferrea; ii) antileishmanial activity of extracts from L. ferrea against promastigotes and amastigotes of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) guyanensis; iii) the effects of topical treatment using hydrogel containing active extract of L. ferrea on golden hamsters infected with L. (L.) amazonensis. Extracts from leaves, branches and fruits of L. ferrea were obtained with hexane and methanol and were tested by in vitro assays in promastigotes and murine macrophages J774 experimentally infected with amastigotes of Leishmania. Groups of hamsters with CL received topical treatment with a formulation of extract (10%) hydrogels, 50 mg.day ) e baixa citotoxicidade em células de macrófagos J774. Os resultados destacaram que as lesões cutâneas de animais que receberam tratamento com hidrogel + extrato (GelFrMeOH) apresentaram redução significativa (42,78%), menos úlceração e redução da carga parasitária detectada por RT-qPCR, microscopia e análise em cultura e alterações histopatológicas, como menor infiltrado inflamatório após 40 dias de tratamento. A análise química demonstrou que FrMeOH contém altos níveis de compostos fenólicos. Os resultados apontam para uma possível terapia alternativa para CL utilizando fitoterápicos. PALAVRAS-CHAVE: leishmaniose cutânea, formulações tópicas, produtos naturais, tratamento experimental

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Section: Discussionmentioning

confidence: 98%

Antileishmanial activity of extracts from Libidibia ferrea: development of in vitro and in vivo tests

et al. 2017

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“…Information about the topical use of pentamidine was scarce. A topical application of 10% PMD isethionate and 10% usnic acid cream over eight consecutive days reduced lesion size (reduction of 27.37%) and parasite numbers in L. (L.) amazonensis -infected hamsters, compared to controls 28 . In addition, intralesional PMD isethionate (three injections of 120 μg/mm 2 to the lesion area over five days) has resulted in a cure rate of 72% for Bolivian L. (V.) braziliensis- infected patients 29 …”

Section: Discussionmentioning

confidence: 99%

Therapeutic response and safety of the topical, sequential use of antiseptic, keratolytic, and pentamidine creams (3-PACK) on Leishmania (Viannia) braziliensis-infected mice

Muñoz

Mantilla

Escobar

2019

Mem. Inst. Oswaldo Cruz

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BACKGROUND Topical treatment of New World cutaneous leishmaniasis can be affected by bacterial coinfection, hyperkeratosis, and transdermal drug delivery. OBJECTIVE The aim of this work was to evaluate the therapeutic response and safety of the topical, sequential use of antiseptic, keratolytic, and pentamidine isethionate (PMD) creams (3-PACK kit) on CL-infected BALB/c mice. METHODS A 0.5% chlorhexidine solution (CGH), 10% salicylic acid (SA), and 3% or 6% PMD were used as antiseptic, keratolytic, and antileishmanial drugs, respectively. During the first seven days, antiseptic, followed by 10% SA gel and PMD cream, were applied topically. Subsequently, treatment was performed only with the antiseptic and PMD creams. Skin irritation, reduction of lesion size (mm 2 ), and parasitic load were observed until 30 days of treatment were completed. FINDINGS The 3-PACK treatment using 6% PMD induced a complete lesion reduction in 3/6 mice and a partial reduction in 1/6 mice, with no parasites observed. In contrast, CGH and SA alone, along with the vehicle, were not effective (p < 0.05). Moderate to severe erythema was observed at the application site. MAIN CONCLUSION The topical 3-PACK using 6% PMD was 67% effective in the treatment of CL by Leishmania (Viannia) braziliensis . Currently, work is ongoing to improve PMD isethionate formulation and to determine a dose-response.

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“…A tissue sample sectioned from the lesion area of each animal was also used for an impression on glass slides. The slides were stained with Giemsa (Sigma), and the infectivity index was determined by multiplying the percentage of macrophages having at least one intracellular parasite by the average number of intracellular parasites per infected macrophage (at least 200 cells/animal were examined) [ 48 , 49 , 50 ].…”

Section: Methodsmentioning

confidence: 99%

Antileishmanial Activity of Clinanthus milagroanthus S. Leiva & Meerow (Amaryllidaceae) Collected in Peru

Soto-Vásquez

Alvarado-García

Osorio

et al. 2023

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Leishmaniasis is a worldwide infectious parasitic disease caused by different species of protozoa of the genus Leishmania, which are transmitted to animals and humans through the bite of insects of the Psychodidae family. In the present work, the antileishmanial activity of an alkaloid extract of the bulbs of Clinanthus milagroanthus S. Leiva & Meerow (Amaryllidaceae) was evaluated in vitro, in vivo, and in silico against the parasite Leishmania braziliensis, and the chemical profile of the sample was determined by GC-MS analysis. At concentrations of 1, 10, and 100 µg·mL−1, the alkaloid extract presented inhibition percentages of 8.7%, 23.1%, and 98.8%, respectively, against L. braziliensis with a p < 0.05, and IC50 values of 18.5 ± 0.3 µg·mL−1. Furthermore, at a dose of 1.0 mg·kg−1, a greater decrease in lesion size was observed (90%) for in vivo assays, as well as a decrease in infection (96%), finding no significant differences (p > 0.05) in comparison with amphotericin B (92% and 98%, respectively). Eleven alkaloids were identified in C. milagroanthus bulbs: galanthamine, vittatine/crinine, 8-O-demethylmaritidine, anhydrolycorine, 11,12-dehydroanhydrolycorine, hippamine, lycorine, 2-hydroxyanhydrolycorine, 7-hydroxyclivonine, 2α-hydroxyhomolycorine, and 7-hydroxyclivonine isomer. A molecular model of Leishmania braziliensis trypanothione reductase (TRLb) was built using computational experiments to evaluate in silico the potential of the Amaryllidaceae alkaloid identified in C. milagroanthus toward this enzyme. The structures galanthamine, 7-hydroxyclivonine isomer, and crinine showed better estimated free energy of binding than the reference compound, amphotericin B. In conclusion, this is the first in vitro, in vivo, and in silico report about the antileishmanial potential and alkaloid profiling of the extract of C. milagroanthus bulbs, which could become an interesting source of bioactive molecules.

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Topical treatment of experimental cutaneous leishmaniasis in golden hamster (Mesocricetus auratus) with formulations containing pentamidine

Cited by 3 publications

References 26 publications

Antileishmanial activity of extracts from Libidibia ferrea: development of in vitro and in vivo tests

Antileishmanial activity of extracts from Libidibia ferrea: development of in vitro and in vivo tests

Therapeutic response and safety of the topical, sequential use of antiseptic, keratolytic, and pentamidine creams (3-PACK) on Leishmania (Viannia) braziliensis-infected mice

Antileishmanial Activity of Clinanthus milagroanthus S. Leiva & Meerow (Amaryllidaceae) Collected in Peru

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