Cellular Markers for the Identification of Chemoresistant Isolates in Leishmania

Padrón-Nieves, Maritza; Ponte-Sucre, Alicia

doi:10.1007/978-1-0716-0294-2_44

Cited by 2 publications

(2 citation statements)

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“…To evaluate the plasma membrane potential (ΔΨp), the fluorescent compound, bisoxonol, bis[1,3-diethylthiobarbituric acid] trimethine oxonol, was used, as well as a method [ 41 ] optimized by Padrón-Nieves et al [ 42 , 43 , 44 ]. Initially, calibration curves for each strain, using increasing concentrations of KCl (0.5 to 75 mM), were performed in the late log growth phase Leishmania promastigotes in the presence of the potassium ionophore valinomycin.…”

Section: Methodsmentioning

confidence: 99%

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Leishmanicidal Activity of Betulin Derivatives in Leishmania amazonensis; Effect on Plasma and Mitochondrial Membrane Potential, and Macrophage Nitric Oxide and Superoxide Production

et al. 2021

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Herein, we evaluated in vitro the anti-leishmanial activity of betulin derivatives in Venezuelan isolates of Leishmania amazonensis, isolated from patients with therapeutic failure. Methods: We analyzed promastigote in vitro susceptibility as well as the cytotoxicity and selectivity of the evaluated compounds. Additionally, the activity of selected compounds was determined in intracellular amastigotes. Finally, to gain hints on their potential mechanism of action, the effect of the most promising compounds on plasma and mitochondrial membrane potential, and nitric oxide and superoxide production by infected macrophages was determined. Results: From the tested 28 compounds, those numbered 18 and 22 were chosen for additional studies. Both 18 and 22 were active (GI50 ≤ 2 µM, cytotoxic CC50 > 45 µM, SI > 20) for the reference strain LTB0016 and for patient isolates. The results suggest that 18 significantly depolarized the plasma membrane potential (p < 0.05) and the mitochondrial membrane potential (p < 0.05) when compared to untreated cells. Although neither 18 nor 22 induced nitric oxide production in infected macrophages, 18 induced superoxide production in infected macrophages. Conclusion: Our results suggest that due to their efficacy and selectivity against intracellular parasites and the potential mechanisms underlying their leishmanicidal effect, the compounds 18 and 22 could be used as tools for designing new chemotherapies against leishmaniasis.

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Section: Methodsmentioning

confidence: 99%

“…This was done for the reference strain LTB0016, as well as for the patient isolates. Finally, to calculate the plasma membrane potential, the Nernst equation was used [ΔΨp = −59.4 log(120/[KCl])] [ 42 , 43 , 44 ].…”

Section: Methodsmentioning

confidence: 99%