Effects of Specific Electric Field Stimulation on the Release and Activity of Secreted Acid Phosphatases from Leishmania tarentolae and Implications for Therapy

Dorsey, Benjamin M.; Cass, Cynthia L.; Cedeño, David L.; Vallejo, Ricardo; Jones, Marjorie A.

doi:10.3390/pathogens7040077

Cited by 9 publications

(9 citation statements)

References 20 publications

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“…We have previously reported that Leishmania tarentolae are able to synthesize nitric oxide [ 15 ]. This is especially of interest since there are reports that both nitric oxide production and secreted acid phosphatase are linked to successful parasite-host interactions [ 15 , 16 ]. We can thus speculate that a modest decrease in parasite virulence is likely in regions richer in strontium and perhaps bismuth.…”

Section: Discussionmentioning

confidence: 99%

Leishmania tarentolae novel responses to Bi3+-doped strontium aluminum oxyfluorides

Apuzzo

Sullivan

Platt

et al. 2021

Heliyon

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Novel therapeutics for the treatment of leishmaniasis are of interest as the disease not only is becoming more prevalent, but drug resistance is increasing in certain regions of the world. Reported here is the use of Bi 3+ -doped strontium aluminum oxyfluoride phosphors and protease inhibitors to test in vitro inhibitory activity against cultured promastigote Leishmania tarentolae and effects on L. tarentolae secreted acid phosphatase (SAP) activity. Cell viability did not significantly decrease in the presence of 50 μM anti-perovskite compounds, implying limited cytotoxicity. Yet SAP activity did increase in the cell free preparations with time in the presence of strontium compounds. Of interest was the observation that cell free SAP activity did not increase in the presence of protease inhibitors with or without added strontium compounds. Since secreted proteases may play a role in the maturation of Leishmania SAP and thus be involved with parasite-host infection establishment, this is in further need of evaluation. Nitric oxide production on day 4 post-addition of the strontium compounds was evaluated and showed an approximately 50% decrease in NO production in the presence of two test compounds relative to DMSO control cells. This is the first report of anti-perovskite compound inhibition of NO production by Leishmania .

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Section: Discussionmentioning

confidence: 99%

Leishmania tarentolae novel responses to Bi3+-doped strontium aluminum oxyfluorides

Apuzzo

Sullivan

Platt

et al. 2021

Heliyon

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“…SAP Enzyme Kinetic Assay using Selected Test Compounds (following the method of Dorsey et al . [ 28 ]): A stock culture of L. tarentolae in the late stationary phase, was pelleted, retaining the supernatant. This standard pool of SAP enzyme was separated into equal volumes and allowed to incubate with 30 µM compounds 6 , 1c , and 1e .…”

Section: Methodsmentioning

confidence: 99%

“…This strain of Leishmania is generally regarded as non-pathogenic to humans, and it therefore serves as a model system in vitro [ 26 ]. We observed that these compounds negatively affect parasite growth and viability in vitro with mechanistic targets such as nitric oxide production and secreted acid phosphatase activity, both of which are proposed to be involved in parasite-host interactions [ 27 , 28 ]. We also included tests against mammalian glial cells, in culture, to evaluate toxicity for another cell type.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Polycyclic Ether-Benzopyrans and In Vitro Inhibitory Activity against Leishmania tarentolae

et al. 2020

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Construction of a focused library of polycyclic ether-benzopyrans was undertaken in order to discover new therapeutic compounds that affect Leishmania growth and infectivity. This is especially of interest since there are few drug therapies for leishmaniasis that do not have serious drawbacks such high cost, side effects, and emerging drug resistance. The construction of these polycyclic ether-benzopyrans utilized an acetoxypyranone-alkene [5+2] cycloaddition and the Suzuki-Miyaura cross-coupling. The multi-gram quantity of the requisite aryl bromide was obtained followed by effective Pd-catalyzed coupling with boronic acid derivatives. Compounds were tested in vitro using the parasitic protozoan, Leishmania tarentolae. Effects of concentration, time, and exposure to light were evaluated. In addition, the effects on secreted acid phosphatase activity and nitric oxide production were investigated, since both have been implicated in parasite infectivity. The data presented herein are indicative of disruption of the Leishmania tarentolae and thus provide impetus for the development and testing of a more extensive library.

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“…In leishmaniasis, the use of therapeutic electricity applied on infected mice with L. major showed important death of parasites at the lesion sites [91]. Recent advances have demonstrated that electric fields affected leishmania tarentolae promastigote motility, clumping and viability in vitro [92]. However, these studies are in an initial phase requiring more data related to what currents, potentials, numbers of stimulations, and durations are safe but effective for clinical use against CL.…”

Section: Electrotherapymentioning

confidence: 99%

Current Strategies and Recent Advances in Nanostructured Delivery Systems for Managing Leishmaniasis-a Review

Chaurasia

Jain

2022

JASR

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Neglected tropical diseases (NTDs) comprise of a group of 17th infectious conditions endemic in many developing countries. Among these diseases, deadly, prevalent parasitic infection such as leishmaniasis, presents a significant global burden which is responsible for high morbidity/mortality rate especially in low-and middle-income/developed countries transmitted by phlebotomines sandflies. As per the WHO report, a total of 0.7-1.0 million new leishmaniasis cases, which are spread by 23 leishmania species in more than 98 countries are estimated with an alarming 26,000-65,000 death toll every year. The disease can be characterized by at least four syndromes: cutaneous leishmaniasis (CL), muco-cutaneous leishmaniasis (MCL), visceral leishmaniasis (VL) also known as kala-azar in the Indian sub-continent or black fever, which is the most firm form of the disease being lethal if untreated and post-kala-azar dermal leishmaniasis (PKDL). The lack of cheap, portable, easy to use diagnostic tools exhibiting high efficiency and specificity impede the early diagnosis of the disease. Its intracellular nature and disseminated locations of parasite, limited number of chemotherapeutic agents, increasing incidences of resistance to first line drugs, along with the cost, toxicities, low patient compliance and require long-term regimen and usually hospitalization, pose a great challenge to formulation scientists that have necessitated effective management of leishmaniasis infection by modulating the delivery of existing drugs. Over the past decade, research on development of alternative treatments such as nanotechnology-based drug delivery systems (nanoparticles, nanotubes, nanosuspensions, liposomes, nanovaccines, etc.), use of natural products as well as development of antileishmanial vaccine has been extensively investigated due to their unique properties, such as bioavailability, lowered toxicity, targeted drug delivery, high biocomatibilty and biodegradability. To identify all relevant literature, we searched Web of Sciences, Scopus, PubMed, NCBI, Scielo, Google Scholar, and profiled studies published between 1986 and 2020. The aim of this review is to summarize new advances and new strategies used on leishmaniasis therapy addressing alternative and innovative treatment paths such as combination or multi-drug uses, immunomodulation, drug repurposing and the nanotechnology-based drug delivery systems have been used to improve the therapeutic aspects of existing antileishmanial drugs, presenting a critical review and some suggestions for improving drug delivery.

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Effects of Specific Electric Field Stimulation on the Release and Activity of Secreted Acid Phosphatases from Leishmania tarentolae and Implications for Therapy

Cited by 9 publications

References 20 publications

Leishmania tarentolae novel responses to Bi3+-doped strontium aluminum oxyfluorides

Leishmania tarentolae novel responses to Bi3+-doped strontium aluminum oxyfluorides

Synthesis of Polycyclic Ether-Benzopyrans and In Vitro Inhibitory Activity against Leishmania tarentolae

Current Strategies and Recent Advances in Nanostructured Delivery Systems for Managing Leishmaniasis-a Review

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