Photodynamic therapy for American cutaneous leishmaniasis: The efficacy of methylene blue in hamsters experimentally infected with Leishmania (Leishmania) amazonensis

Peloi, Lílian Somenci; Biondo, Carlos Eduardo Guerino; Kimura, Elza; Politi, Mário José; Lonardoni, Maria Valdrinez Campana; Aristides, Sandra Mara Alessi; Dórea, R. C. C.; Hioka, Noboru; Silveira, Thaís Gomes Verzignassi

doi:10.1016/j.exppara.2011.04.009

Cited by 73 publications

(55 citation statements)

References 29 publications

(32 reference statements)

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“…Anti-Leishmania PDT has been assessed experimentally in vivo in different animal models of CL and in vitro in infected macrophages. More recent work includes the use of different photosensitizers, e.g., hypericin, phthalocyanines, phenothiazines, methylene blue, and zinc oxide, as such or after PEGylation or in liposome-/nanoparticle-encapsulated forms, to generate ROS by illumination using different light sources, e.g., light-emitting diodes (LED), lasers, and sunlight (9)(10)(11)(12)(13)(14)(15)(16)(17). The intrinsic susceptibilities of both stages of Leishmania, i.e., promastigotes and amastigotes, to PDT has been examined in that context but rarely has been explored at the cellular and molecular levels.…”

mentioning

confidence: 99%

Aminophthalocyanine-Mediated Photodynamic Inactivation of Leishmania tropica

Al‐Qahtani

Alkahtani

Kolli

et al. 2016

Antimicrob Agents Chemother

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dPhotodynamic inactivation of Leishmania spp. requires the cellular uptake of photosensitizers, e.g., endocytosis of silicon(IV)-phthalocyanines (PC) axially substituted with bulky ligands. We report here that when substituted with amino-containing ligands, the PCs (PC1 and PC2) were endocytosed and displayed improved potency against Leishmania tropica promastigotes and axenic amastigotes in vitro. The uptake of these PCs by both Leishmania stages followed saturation kinetics, as expected. Sensitive assays were developed for assessing the photodynamic inactivation of Leishmania spp. by rendering them fluorescent in two ways: transfecting promastigotes to express green fluorescent protein (GFP) and loading them with carboxyfluorescein succinimidyl ester (CFSE). PC-sensitized Leishmania tropica strains were seen microscopically to lose their motility, structural integrity, and GFP/CFSE fluorescence after exposure to red light (wavelength, ϳ650 nm) at a fluence of 1 to 2 J cm ؊2 . Quantitative fluorescence assays based on the loss of GFP/CFSE from live Leishmania tropica showed that PC1 and PC2 dose dependently sensitized both stages for photoinactivation, consistent with the results of a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay. Leishmania tropica strains are >100 times more sensitive than their host cells or macrophages to PC1-and PC2-mediated photoinactivation, judging from the estimated 50% effective concentrations (EC 50 s) of these cells. Axial substitution of the PC with amino groups instead of other ligands appears to increase its leishmanial photolytic activity by up to 40-fold. PC1 and PC2 are thus potentially useful for photodynamic therapy of leishmaniasis and for oxidative photoinactivation of Leishmania spp. for use as vaccines or vaccine carriers.

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confidence: 99%

Aminophthalocyanine-Mediated Photodynamic Inactivation of Leishmania tropica

Al‐Qahtani

Alkahtani

Kolli

et al. 2016

Antimicrob Agents Chemother

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“…The animals of MB-Id and MB-Tp groups were treated 3 times a week, during 12 weeks. 12 Evaluation of the Lesion The evaluation of the lesion was performed weekly by measuring the thickness of the footpad (infected and non-infected footpad) with a thickness gauge (Mitutoyo, Japan) and the difference between the measurements were calculated. Photographies of the lesions were taken monthly.…”

Section: Chemical and Led Lightmentioning

confidence: 99%

“…10,11 MB presents little harm to the patient in the treatment, and its toxic potential can be activated by light. 12 MB is also employed as medications for the treatment of methemoglobinemia (injected intravenously) and other diseases. Thus, this study aimed to evaluate the PDT using MB and LED in the treatment of ACL in hamsters infected with Leishmania braziliensis.…”

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confidence: 99%

Topical and Intradermal Efficacy of Photodynamic Therapy with Methylene Blue and Light-Emitting Diode in the Treatment of Cutaneous Leishmaniasis Caused by Leishmania braziliensis

et al. 2015

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“…Both compounds were also effective in hamsters infected with L. (L.) amazonensis, with a cure efficiency between 80 and 100% (10). Toluidine blue, methylene blue, and phenothiazine have also been shown to have in vitro activity against Leishmania (Viannia) braziliensis promastigotes (15,16). When evaluated in hamsters infected with L. (L.) amazonensis, methylene blue induced reduction in lesion size but low cure rates (40% to 50%) (16).…”

mentioning

confidence: 99%

“…Toluidine blue, methylene blue, and phenothiazine have also been shown to have in vitro activity against Leishmania (Viannia) braziliensis promastigotes (15,16). When evaluated in hamsters infected with L. (L.) amazonensis, methylene blue induced reduction in lesion size but low cure rates (40% to 50%) (16). Meanwhile, aluminum phthalocyanine chloride showed in vitro leishmanicidal activity against intracellular amastigotes of L. (V.) panamensis and L. (L.) infantum (17,18).…”

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confidence: 99%

Development of a Novel Formulation with Hypericin To Treat Cutaneous Leishmaniasis Based on Photodynamic Therapy inIn VitroandIn VivoStudies

Montoya

Daza

Muñoz

et al. 2015

Antimicrob Agents Chemother

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An evaluation of the leishmanicidal activity in vitro and in vivo of hypericin, an expanded-spectrum photosensitizer found in Hypericum perforatum, is presented. Hypericin was evaluated against intracellular amastigotes in vitro of Leishmania (Viannia) panamensis. A topical formulation containing 0.5% hypericin was developed and assayed in vivo in a hamster model of cutaneous leishmaniasis. Results demonstrate that hypericin induces a significant antiamastigote effect in vitro against L. panamensis by decreasing the number of parasites inside infected cells. The topical formulation of 0.5% hypericin allows healing of L. panamensis-induced lesions upon a topical application of 40 mg/day plus visible-light irradiation (5 J/cm 2 , 15 min), twice a week for 3 weeks. Cutaneous leishmaniasis (CL) is a parasitic disease caused by protozoa of the genus Leishmania, which manifests as a chronic infection affecting mainly mononuclear phagocytes of the skin (1). The disease affects the poorest populations in 99 countries in tropical and subtropical regions of the world (2, 3). It is estimated that 14 million people are infected, 350 million are at risk, and there are about 1.5 million new cases per year (3, 4). The parasite is transmitted by the bite of an insect vector belonging to the genus Lutzomyia (in America) or Phlebotomus (in Europe, Asia, and Africa) in the subfamily Phlebotominae (5).Only three types of drugs are available to treat CL. They are the pentavalent antimonials (meglumine antimoniate and sodium stibogluconate), pentamidine isethionate, and miltefosine. Miltefosine is the only one available for oral administration (4). These medications are delivered at high doses and for long periods, thus leading to high toxicity. Therefore, their use is contraindicated in pregnant women, in patients with cardiovascular, renal, or hepatic disease, and in children with low body weight (6). Overall, the efficacy of these drugs varies between 55 and 98% depending on the compound and on the Leishmania species causing the clinical manifestation (7,8). However, their elevated toxicity encourages abandonment of treatment and consequently a decrease in the efficacy (9).More recently, photodynamic therapy (PDT) has emerged as an alternative to treat CL (10). This therapy is based on the application of a photosensitizing agent (PA) that, when excited by light of a certain wavelength, induces the production of reactive oxygen species (ROS) that can destroy the microorganism or the target cell (11). In spite of its potential, only a few PAs have been tested against CL in animal models, and only one in humans. Topical application of 5-aminolevulinic acid (ALA) and light in a murine model of CL caused by L. major showed a significant reduction of the parasitic load and the size of lesions (12). Intralesional administration of ALA (one to three PDT sessions) in a patient with CL by L. major produced a 10 to 20% cure, although it is probable that clinical outcome resulted from nonspecific destruction of infected macrophages instead of...

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Photodynamic therapy for American cutaneous leishmaniasis: The efficacy of methylene blue in hamsters experimentally infected with Leishmania (Leishmania) amazonensis

Cited by 73 publications

References 29 publications

Aminophthalocyanine-Mediated Photodynamic Inactivation of Leishmania tropica

Aminophthalocyanine-Mediated Photodynamic Inactivation of Leishmania tropica

Topical and Intradermal Efficacy of Photodynamic Therapy with Methylene Blue and Light-Emitting Diode in the Treatment of Cutaneous Leishmaniasis Caused by Leishmania braziliensis

Development of a Novel Formulation with Hypericin To Treat Cutaneous Leishmaniasis Based on Photodynamic Therapy inIn VitroandIn VivoStudies

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