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PLoS Negl Trop Dis. 2016 Mar 29;10(3):e0004525. doi: 10.1371/journal.pntd.0004525. eCollection 2016 Mar.

Allicin Induces Calcium and Mitochondrial Dysregulation Causing Necrotic Death in Leishmania.

Author information

1
Department of Animal Health, Group ICPVet, Faculty of Veterinary Medicine, University Complutense Madrid, Spain.
2
Department of Analytical Chemistry, Optical Chemosensors and Applied Photochemistry Group (GSOLFA), University Complutense Madrid, Spain.
3
National Microbiology Centre, Institute of Health Carlos III (ISCIII), Majadahonda, Madrid, Spain.

Abstract

BACKGROUND:

Allicin has shown antileishmanial activity in vitro and in vivo. However the mechanism of action underlying its antiproliferative effect against Leishmania has been virtually unexplored. In this paper, we present the results obtained in L.infantum and a mechanistic basis is proposed.

METHODOLOGY/PRINCIPAL FINDING:

Exposure of the parasites to allicin led to high Ca2+ levels and mitochondrial reactive oxygen species (ROS), collapse of the mitochondrial membrane potential, reduced production of ATP and elevation of cytosolic ROS. The incubation of the promastigotes with SYTOX Green revealed that decrease of ATP was not associated with plasma membrane permeabilization. Annexin V and propidium iodide (PI) staining indicated that allicin did not induce phospholipids exposure on the plasma membrane. Moreover, DNA agarose gel electrophoresis and TUNEL analysis demonstrated that allicin did not provoke DNA fragmentation. Analysis of the cell cycle with PI staining showed that allicin induced cell cycle arrest in the G2/M phase.

CONCLUSIONS/SIGNIFICANCE:

We conclude that allicin induces dysregulation of calcium homeostasis and oxidative stress, uncontrolled by the antioxidant defense of the cell, which leads to mitochondrial dysfunction and a bioenergetic catastrophe leading to cell necrosis and cell cycle arrest in the premitotic phase.

PMID:
27023069
PMCID:
PMC4811430
DOI:
10.1371/journal.pntd.0004525
[Indexed for MEDLINE]
Free PMC Article

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