Abstract
BackgroundAllicin 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 FindingExposure 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/SignificanceWe 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.
Highlights
Leishmaniases are vectorial parasitic diseases of mammals, including humans, caused by Leishmania species and present in all inhabited continents
Leishmaniasis is a vectorial parasitic disease caused by flagellate organisms from the genus Leishmania
A molecule obtained from garlic, has shown antiproliferative effect against different cancer cells, bacteria, fungi and Protista including Leishmania
Summary
Leishmaniases are vectorial parasitic diseases of mammals, including humans, caused by Leishmania species and present in all inhabited continents. 350 million [1] and 3.4 billion people [2] living in areas at risk. It is considered the second most lethal parasitic disease, after malaria, visceralizing species being responsible of 20,000 to 40,000 human deaths per year [3]. In the last years a rise in human prevalence has been found, the disease extending to previously exempt areas. Control of infections relies on chemotherapy but these drugs have several shortcomings including high price, length of treatments and side effects such as toxicity and teratogenicity [4]. We present the results obtained in L.infantum and a mechanistic basis is proposed
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