Comparison of intralesional two percent zinc sulfate and glucantime injection in treatment of acute cutaneous leishmaniasis

Maleki, Masoud; Karimi, Gholamreza; Tafaghodi, Mohsen; Raftari, Somayyeh; Nahidi, Yalda

doi:10.4103/0019-5154.94279

Cited by 18 publications

(11 citation statements)

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“…To determine the cytotoxic concentration of the compounds combined with divalent metal ion salts, we quantified the ATP present in metabolically active HepG2 cells. The addition of divalent metal ion salts increased the cytotoxicity of disulfiram and CID 7188 (CC 50 ). This was greatest with AgNO 3 and CuSO 4 (CC 50 Յ 10 M; Tables 4 and 5).…”

Section: Resultsmentioning

confidence: 99%

“…It may be due to differences in host cell cytotoxicity between the hamster (L. donovani) and mouse (L. major) ex vivo explant screening systems. To address this, we infected mouse macrophages (RAW 264.7 cell line) with L. major or L. donovani and determined the EC 50 . Again, we found very good enhancement activity of the compounds with ZnCl 2 (Ͼ3-fold reduction in the EC 50 for both Leishmania species).…”

Section: Resultsmentioning

confidence: 99%

“…To address this, we infected mouse macrophages (RAW 264.7 cell line) with L. major or L. donovani and determined the EC 50 . Again, we found very good enhancement activity of the compounds with ZnCl 2 (Ͼ3-fold reduction in the EC 50 for both Leishmania species). ZnSO 4 also modestly improved the EC 50 .…”

Section: Resultsmentioning

confidence: 99%

“…The percentage of parasite inhibition with regard to controls was calculated as ϭ 100 Ϫ [(parasite counts in treated cells/parasite counts in untreated cells) ϫ 100]. The EC 50 was determined by regression analysis using GraphPad (Prism 5.0), and the means and standard errors from three different experiments were utilized to estimate the final EC 50 .…”

Section: Methodsmentioning

confidence: 99%

“…Cell toxicity (CC 50 ) and calculation of the IVTI. We used the HepG2 cell line (human hepatocellular carcinoma, ATCC HB-8065) as a cellbased assay and an alternative to animal testing to determine toxicity of disulfiram and its analogs (39,40).…”

Section: Methodsmentioning

confidence: 99%

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Antileishmanial Activity of Disulfiram and Thiuram Disulfide Analogs in anEx VivoModel System Is Selectively Enhanced by the Addition of Divalent Metal Ions

Peniche

Renslo

Melby

et al. 2015

Antimicrob Agents Chemother

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dCurrent treatments for cutaneous and visceral leishmaniasis are toxic, expensive, difficult to administer, and limited in efficacy and availability. Disulfiram has primarily been used to treat alcoholism. More recently, it has shown some efficacy as therapy against protozoan pathogens and certain cancers, suggesting a wide range of biological activities. We used an ex vivo system to screen several thiuram disulfide compounds for antileishmanial activity. We found five compounds (compound identifier [CID] 7188, 5455, 95876, 12892, and 3117 [disulfiram]) with anti-Leishmania activity at nanomolar concentrations. We further evaluated these compounds with the addition of divalent metal salts based on studies that indicated these salts could potentiate the action of disulfiram. In addition, clinical studies suggested that zinc has some efficacy in treating cutaneous leishmaniasis. Several divalent metal salts were evaluated at 1 M, which is lower than the normal levels of copper and zinc in plasma of healthy individuals. The leishmanicidal activity of disulfiram and CID 7188 were enhanced by several divalent metal salts at 1 M. The in vitro therapeutic index (IVTI) of disulfiram and CID 7188 increased 12-and 2.3-fold, respectively, against L. major when combined with ZnCl 2 . The combination of disulfiram with ZnSO 4 resulted in a 1.8-fold increase in IVTI against L. donovani. This novel combination of thiuram disulfides and divalent metal ions salts could have application as topical and/or oral therapies for treatment of cutaneous and visceral leishmaniasis.T he leishmaniases are vector-borne parasitic diseases with a significant global impact. These diseases occur in more than 88 countries of the world, where approximately 350 million people are at risk. In the Old World, visceral and cutaneous leishmaniasis are caused by the intracellular protozoa Leishmania donovani and Leishmania major, respectively. Visceral leishmaniasis is characterized by impaired parasite-specific cell-mediated immunity and progressive hepatosplenomegaly, anemia, and weight loss and is frequently fatal if left untreated (1). In cutaneous leishmaniasis (CL), the disease severity varies considerably from single self-resolving skin nodules or ulcers to one or more nonhealing lesions, which can be disfiguring (2). The healing response is generally associated with expansion of parasite-specific gamma interferon (IFN-␥)-producing T cells (3).All currently available drug therapies for leishmaniasis have potentially harmful side effects and documented limitations in efficacy. The pentavalent antimony compounds, which are still widely used in many countries, are suboptimal because of the difficulty of administration, well-known host toxicity, and increasing parasite drug resistance. Cure rates have been noted recently to be unacceptably low (4). Other therapies, including amphotericin B desoxycholate and its liposomal formulation, and miltefosine, have been increasingly used in the treatment of visceral or cutaneous leishmaniasis. Their use is al...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%