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Updated: Sep 21, 2025
In Vivo Infection with Leishmania amazonensis to Evaluate Parasite Virulence in Mice
Published on: February 20, 2020
Ivermectin and curcumin cause plasma membrane rigidity in Leishmania amazonensis due to oxidative stress
Lais Alonso1, Miriam Leandro Dorta2, Antonio Alonso1
1Instituto de Física, Universidade Federal de Goiás, Goiânia, GO, Brazil.
Abstract:
Spin label electron paramagnetic resonance (EPR) spectroscopy was used to study the mechanisms of action of ivermectin and curcumin against Leishmania (L.) amazonensis promastigotes. EPR spectra showed that treatment of the parasites with both compounds results in plasma membrane rigidity due to oxidative processes. With the IC50 and EPR measurements for assays using different parasite concentrations, estimations could be made for the membrane-water partition coefficient (KM/W), and the concentration of the compound in the membrane (cm50) and in the aqueous phase (cw50), which inhibits cell growth by 50%. The KM/W values indicated that ivermectin has a greater affinity than curcumin for the parasite membrane. Therefore, the activity of ivermectin was higher for experiments with low cell concentrations, but for concentrations greater than 1.5 × 108 parasites/mL the compounds did not show significantly different results. The cm50 values indicated that the concentration of compound in the membrane leading to growth inhibition or membrane alteration is approximately 1 M for both ivermectin and curcumin. This high membrane concentration suggests that many ivermectin molecules per chlorine channel are needed to cause an increase in chlorine ion influx.
Insights
Ivermectin and curcumin increase parasite membrane rigidity through oxidative processes. Ivermectin shows higher membrane affinity, but both drugs exhibit similar efficacy at high Leishmania (L.) amazonensis concentrations.
Area of Science:
- Biochemistry
- Parasitology
- Spectroscopy
Background:
- Leishmania (L.) amazonensis is a parasite causing leishmaniasis.
- Ivermectin and curcumin are compounds with potential antiparasitic activity.
- Understanding their mechanism of action is crucial for developing new treatments.
Purpose of the Study:
- To investigate the action mechanisms of ivermectin and curcumin against Leishmania (L.) amazonensis.
- To determine the effect of these compounds on parasite membrane properties.
- To quantify drug-membrane interactions and their impact on parasite growth.
Main Methods:
- Spin label electron paramagnetic resonance (EPR) spectroscopy was employed.
- Parasite growth inhibition assays were performed to determine IC50 values.
- Membrane-water partition coefficient (K_M/W) was estimated.
Main Results:
- Both ivermectin and curcumin induced plasma membrane rigidity in parasites via oxidative processes.
- Ivermectin demonstrated a higher affinity for the parasite membrane compared to curcumin.
- At high parasite concentrations (>1.5 x 10^8 parasites/mL), the efficacy of both compounds was comparable.
- The concentration of either compound within the membrane required for 50% growth inhibition (c_m50) was approximately 1 M for both.
Conclusions:
- Ivermectin and curcumin exert their antiparasitic effects by altering parasite membrane properties.
- The high concentration of drug within the membrane suggests a complex interaction with cellular targets, potentially involving numerous molecules per target site.
- Drug concentration and parasite density influence the observed efficacy of ivermectin and curcumin.
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