Successful Treatment of Cutaneous Leishmaniasis with Amphotericin B; A Case of Unresponsive to Pentavalent Antimony Therapy

Yeşilova, Yavuz; Turan, Enver; Sürücü, Hacer Altın; Aksoy, Mustafa; Özbilgin, Ahmet

doi:10.5152/tpd.2015.3761

Cited by 6 publications

(6 citation statements)

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“…Nanosilver damage DNA, denature proteins and enzymes and produce free radicals and some studies showed that nanosilver is cytotoxic to several different cell lines [1,38]. The teratogenicity of nanosilver in humans is indistinctive and is not reported in the literature but in vivo (animal studies) and in vitro studies showed nanosilver can exhibit a significant level of toxicity [39]. Nano-mediated drug delivery of plant-derived products is one of the most important strategies for the treatment of visceral leishmaniasis (VL) in the absence of adequate anti-leishmanial drugs.…”

Section: Application Of Nano Drugs In Treatment Of Leishmaniasismentioning

confidence: 99%

“…Nano-mediated drug delivery of plant-derived products is one of the most important strategies for the treatment of visceral leishmaniasis (VL) in the absence of adequate anti-leishmanial drugs. Artemisinin has been traditionally used for the treatment of malaria and has been reported to exhibit anti leishmanial and antitumor activities [2,[38][39][40]. Earlier, it has been proved that formulation of artemisinin-loaded nanoparticles improved its activity against L. donovani amastigotes ex vivo [17].…”

Section: Application Of Nano Drugs In Treatment Of Leishmaniasismentioning

confidence: 99%

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Application of Nano Drugs in Treatment of Leishmaniasis

Shahcheraghi¹

2016

Glob J Infect Dis Clin Res

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Objective: Leishmaniasis is endemic in 88 countries with incidence rate of 1.5-2 million; the most common form of leishmaniasis is cutaneous leishmaniasis (CL) with 1.5 million new cases per year. Correct diagnosis and characterization of the particular parasite is important for evaluating prognosis and prescribing appropriate treatment. The current management of leishmaniasis is drug treatment of patients, to alleviate disease and vector control to reduce its transmission. Also, current treatments for visceral leishmaniasis are unsatisfactory because of their toxicity, resistance and high cost. The purpose of the present study was to review the application of nano drugs in treatment of leishmaniasis. Materials and Methods:it was used as source of research the following databases: MEDLINE, Cochrane Library, Scielo, PubMed and the database of CAPES.Results: It has been proved nanosilver particles with highly small sizes, have a good penetration into the cutaneous lesions and a good efficacy on leishmaniasis.anti-leishmanial therapy [14][15][16][17]. Although glucantime is commonly used for the treatment of leishmaniasis, it has some side effects including increased liver enzymes and electrocardiogram changes [17]. In addition, the drug is expensive, the injection is painful, and research shows that resistance of parasite to glucantime is growing in different parts of the world [17][18][19][20]. The use of nanotechnology is ever-expanding in today's technologically advanced world. This form of technology has many advantages over existing ones in many fields and medicine is one of them [20]. There are numerous devices and mechanisms developed with the aid of nanotechnology that can help cure diseases/disorders in a much better and more efficient manner [21]. The usefulness of nanotechnology can especially be seen in the treatment of infectious diseases [21,22]. This review has investigated the treatment of leishmaniasis by nano drugs. Nano drugs against leishmaniasisNanotechnology must be applied for curing infectious disease like leishmaniasis [22]. Many drugs have been made and are still being discovered, but the protozoan re-emerges showing drug resistance to the effective medications [23]. Nanotechnology has just managed to show its promise in developing a liposomal formulation called amphotericin B for leishmaniasis but has serious side effects and is not cost effective in developing countries [23][24][25]. Initial, nanodelivery systems for delivering chemotherapeutics were nanodisks impregnanted with amphotericin B, polymericnanoparticle loaded with pentamidine, primaquine, and niosomes, which still need validation at the clinical level [25][26][27][28]. There is an urgent need to take up assignments to use effective nanotechnology devices in combating this infectious disease [25][26][27][28].Different mechanisms were proposed for antimicrobial property of nanoparticles [28]. One mechanism is binding of nanoparticle to sulfur/ phosphorus-containing biomolecules such as proteins and DNA, which leads to...

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Section: Application Of Nano Drugs In Treatment Of Leishmaniasismentioning

confidence: 99%

Section: Application Of Nano Drugs In Treatment Of Leishmaniasismentioning

confidence: 99%

Application of Nano Drugs in Treatment of Leishmaniasis

Shahcheraghi¹

2016

Glob J Infect Dis Clin Res

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“…DSÖ'ne göre her yıl çoğu gelişmekte olan ülkelerden yaklaşık 2 milyon yeni vaka bildirilmekte olup12 milyon insanı etkilemektedir [10] . Leishmaniasis tedavisinde beş değerli antimon bileşik-leri, amfoterisin B deoksikolat, miltefosin, paromomisin, sitamaquin, azoller ve pentamidin gibi farklı anti-leishmanial ajanların yanında termoterapi ve kriyoterapi gibi uygulamalar da kullanılmaktadır [19][20][21] .…”

Section: Tartişma Ve Sonuçunclassified

“…Tedavisinde kullanılan beş değerli antimon bileşiklerinin etkinliğinin %90'ın üzerinde olduğu bildirilirken, miyalji, artralji, karın ağrısı, hepatit, pankreatit ve çeşitli laboratuvar değerlerinde yükseklik gibi nadiren lokal ve sistemik yan etkilere neden olabileceği de rapor edilmiştir [21] . Amfoterisin B ise vücutta geniş bir yayılım göstermesi nedeniyle, infüzyon reaksiyonları, nefrotoksisite, hipokalemi ve miyokardit gibi yan etkilere sahiptir ve hasta 4-5 hafta yatarak takip edilmektedir.…”

Section: Tartişma Ve Sonuçunclassified

Investigation of Anti-leishmanial Activity of the Ten Different Hydrazone Derivatives

Direkel¹,

Utku²,

Şahi̇n³

et al. 2016

Kafkas Univ Vet Fak Derg

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ÖzetLeishmaniasis Türkiye ve dünyada önemli paraziter bir hastalıktır. Leishmaniasis tedavisinde sodyum stibogluconate, miltefosin, paramomisin, amfoterisin B ve pentamidin gibi anti-leishmanial ilaçlar kullanılmaktadır. Fakat leishmaniasisin kemoterapisinde kullanılan bu ilaçların nefrotoksik, hepatotoksik ve teratojenik yan etkileri görülebilmektedir. Ayrıca antimon bileşiklerine karşı direnç gelişmesi nedeniyle de yeni terapötik ajanların keşfedilmesi ve geliştirilmesine öncelik verilmesi gerektiği düşünülmüştür. Bu çalışmanın amacı, sentezlenmiş hidrazon yapısındaki on farklı bileşiğin (5a-5j) Leishmania infantum promastigotlarına karşı anti-leishmanial aktivitesinin mikrodilüsyon yöntemiyle belirlenmesidir. Hazırlanan hidrazon bileşikleri, konsantrasyonu 6 µg/ml olacak şekilde RPMI-1640 besiyerlerine eklenmiş ve bileşiklerin mikroplakta konsantrasyon aralığı 3 -0.003 µg/ml olacak şekilde seri dilüsyonları yapılmıştır. Mikroplaklarda mikrodilüsyon besiyeri yöntemi uygulanarak, üzerine hemositometrede hücre sayısı 2.5x10 7 hücre/ml olacak şekilde ayarlanmış standart Leishmania infantum promastigotları eklenerek 27°C'de inkübe edilmiştir. Yirmi saat sonra mikroplakların üzerine alamar mavisi eklenerek 4 saat inkübe edilmiştir. Promastigotların üremesi 24, 48 ve 72. saatlerde değerlendirilmiştir. Kuyucuklarda rengin maviden pembeye dönmesi parazitin ürediği, rengin değişmeden kalması ise parazitin üremediği şeklinde değerlendirilmiştir. Bu çalışmada, Leishmania infantum promastigotlarına karşı en etkili maddelerin 5e, 5g ve 5h bileşikleri (MİK 0.187 µg/ml) olduğu, en etkisiz bileşiğin ise 5i bileşiği (MİK 3 µg/ml) olduğu saptanmıştır. Sentezlenen bileşiklerin ilaç olarak kullanılabilmesi için; gerekli olduğu düşünülen in vitro makrofaj kültüründe Leishmania amastigotlarına karşı etkinliği ve in vivo olarak deneysel hayvan modellerinde kontrol çalışmalarına ihtiyaç vardır. Anahtar sözcükler: Leishmania infantum, Hidrazon, Anti-leismanial aktivite, Alamar mavisi Investigation of Anti-leishmanial Activity of the Ten Different Hydrazone Derivatives AbstractLeishmaniasis is an important parasitic disease in Turkey and the world. Anti-leishmanial drugs such as sodium stibogluconate, miltefosine, paramomycin, amphotericin B, and pentamidine are used for the treatment of leishmaniasis. However, the drugs, used for the chemotheraphy of leishmaniasis, have some side effects such as nephrotoxicity, hepatotoxicity, and teratogenicity. In addition, it is deemed that the discovery and development of the new therapeutic agents must be given priority due to the development of resistance against antimony compounds. The purpose of this study is detecting the anti-leishmanial activity of ten different synthesized hydrazone compounds against Leishmania infantum promastigotes via the microdilution method. The prepared hydrazone compounds, having the concentration of 6 µg/ml, were added to RPMI-1640 media and the dilution of the hydrazone derivates was performed in the wells of microplates in the range of concentrations of 3 -0.003 ...

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“…The underlying barricades towards their failure were high toxicity, delayed drug release and response; inimical side effects and development of resistance towards the available drug regimen [5] [6]. One of the contemporary approaches includes the use of amphotericin B accompanied by emanation of miltefosine as the first oral drug therapy for VL [7]. In the conquest for identifying better leishmanicidal compounds, plant-derived and/or mimicking products have been gaining ground.…”

Section: Introductionmentioning

confidence: 99%

Metalloprotease Gp63 targeting novel glycoside exhibits potential antileishmanial activity

Chakrabarti

Narayana

Joshi

et al. 2020

Preprint

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Visceral Leishmaniasis (VL) and its aggressive cutaneous exacerbation known as Post Kala-azar Dermal Leishmaniasis (PKDL) cause a huge disease burden in tropics and sub-tropic endemic zones worldwide. Contemporary treatment modalities have been associated with various complications. Encouraged from the recent marked antimalarial effects from plant derived glycosides; here we have chemically synthesized a library of diverse Glycoside derivatives (Gly 1-12) and evaluated their inhibitory efficacy against Ag83 strain of Leishmania donovani. In vitro activity of Glycoside-2 (Gly 2) on Ag83 strain, unravelled its prominent anti-leishmanial property with IC50 value of 1.13μM. In-silico studies also unveiled the efficacy of Gly 2 to bind to the membrane surface of parasite. The toxic effect of Gly 2 causes necrosis like death in promastigote by abrogating its proliferation leading to imbalanced redox homeostasis by disruption of mitochondrial membrane potential. Additionally, Gly 2 treatment demonstrated increased susceptibility of parasites towards complement mediated lysis and displayed strong lethal effect on amastigote-macrophage infection model mimicking pathophysiological condition of body. This lead molecule was quite effective against the clinical PKDL strain BS12 with IC50 value of 1.97 μM making it the most suitable drug so far which can target both VL and PKDL simultaneously. Based on the above experimental validations we narrowed our thoughts regarding the potent role of Gly 2 targeting surface protein of L. donovani such as Gp63, a zinc metalloprotease. Further analysis of structure activity relationship (SAR) of these glycoside derivatives, demonstrated exceptional binding affinity of Gly 2 towards Gp63, a zinc metalloprotease of L. donovani; with strong H-bond interactions of Gly 2 with catalytic domain in the α-helix B region of Gp63. The strong confined interactions between Gly 2 and the target protein Gp63 in a physiologically relevant cellular environment was further assessed by Cellular Thermal Shift Assay (CETSA) which corroborated with our previous results. Taken together, this study reports the serendipitous discovery of glycoside derivative Gly 2 with enhanced leishmanicidal activity and proves to be novel chemotherapeutic prototype against VL and PKDL.

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Successful Treatment of Cutaneous Leishmaniasis with Amphotericin B; A Case of Unresponsive to Pentavalent Antimony Therapy

Cited by 6 publications

References 1 publication

Application of Nano Drugs in Treatment of Leishmaniasis

Application of Nano Drugs in Treatment of Leishmaniasis

Investigation of Anti-leishmanial Activity of the Ten Different Hydrazone Derivatives

Metalloprotease Gp63 targeting novel glycoside exhibits potential antileishmanial activity

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