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Updated: Aug 11, 2026

Quantification of Intracellular Growth Inside Macrophages is a Fast and Reliable Method for Assessing the Virulence of Leishmania Parasites
Published on: March 16, 2018
Leishmania sp.: growth and survival are impaired by ion channel blockers
A Ponte-Sucre1, Y Campos, M Fernandez
1Laboratory of Molecular Physiology, I.M.E., Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela.
Abstract:
In the present work we examined the effect of ion transport blockers on the growth and viability of Leishmania sp. and on the infection of macrophages by the parasite. 4-aminopyridine and glibenclamide block voltage-dependent and K+ ATP channels, respectively; amiloride is used to detect Na+ channels and Na+/H+ antiporters; and anthracene-9-carboxylic acid affects chloride channels. The EC50 for promastigote cultures of three strains of the Leishmania subgenus, namely, Leishmania (Leishmania) NR, Leishmania (Leishmania) amazonensis LTB0016, and Leishmania (Leishmania) major, at their stationary phase of growth, were, respectively, 39, 46, and 464 microM for 4-aminopyridine; 7, 0.8, and 10 microM for glibenclamide and 66, 170, and 10 microM for anthracene-9-carboxylic acid. The amiloride EC50 for NR was 264 microM and 10 microM for L. (L.) major, but was never reached for LTB0016. Higher concentrations of the drugs impaired the exponential growth of Leishmania promastigotes. These results suggest the susceptibility of Leishmania sp. to blockers associated with K+ and Cl- and to Na+ or Na+/H+ transport systems. Blockade of such systems might have impaired the survival of the parasites as promastigotes. In addition, it affected the persistence of parasites in host cells. Although the infection of the macrophage cell line J774 and peritoneal-exudate macrophages was not significantly decreased by concentrations of the drugs around the promastigotes' EC50, the survival of intracellular parasites decreased significantly in the presence of these drugs without affecting the viability of the macrophages. Some blockers consistently gave small EC50 and significantly decreased the infection process as well as the survival of intracellular parasites. Thus, elucidation of their mechanism of action in Leishmania is relevant, since they could represent a potential subject for the development of leishmanicidal drugs.
Insights
Ion transport blockers, including those affecting potassium (K+) and chloride (Cl-) channels, show promise in combating Leishmania parasites. These compounds inhibit parasite growth and reduce intracellular survival, suggesting potential for new leishmanicidal drug development.
Area of Science:
- Parasitology
- Molecular Biology
- Drug Discovery
Background:
- Leishmania parasites cause leishmaniasis, a significant global health concern.
- Understanding parasite ion transport mechanisms is crucial for developing novel treatments.
- Existing treatments for leishmaniasis have limitations, necessitating new therapeutic strategies.
Purpose of the Study:
- To investigate the impact of ion transport blockers on Leishmania parasite growth and macrophage infection.
- To evaluate the efficacy of specific blockers targeting potassium (K+), sodium (Na+), and chloride (Cl-) channels.
- To explore the potential of these blockers as candidates for leishmanicidal drug development.
Main Methods:
- Tested the effects of 4-aminopyridine, glibenclamide, amiloride, and anthracene-9-carboxylic acid on Leishmania promastigote cultures.
- Determined the half-maximal effective concentration (EC50) for each drug across three Leishmania strains.
- Assessed the impact of these blockers on macrophage infection and intracellular parasite survival.
Main Results:
- The study identified varying EC50 values for different ion transport blockers across Leishmania strains.
- Higher drug concentrations inhibited the exponential growth of Leishmania promastigotes.
- Blockers targeting K+, Cl-, and Na+/H+ transport systems significantly reduced intracellular parasite survival without harming macrophages.
Conclusions:
- Leishmania parasites are susceptible to ion transport blockers, particularly those affecting K+ and Cl- channels.
- These blockers demonstrate potential for inhibiting parasite growth and intracellular persistence.
- Further research into the mechanisms of these blockers could lead to the development of new leishmanicidal drugs.
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