title: Allicin Induces Calcium and Mitochondrial Dysregulation Causing Necrotic Death in Leishmania.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Animal Health, Group ICPVet, Faculty of Veterinary Medicine, University Complutense Madrid, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Corral
authors.affiliation: Department of Analytical Chemistry, Optical Chemosensors and Applied Photochemistry Group (GSOLFA), University Complutense Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Benito-Peña
authors.affiliation: Department of Animal Health, Group ICPVet, Faculty of Veterinary Medicine, University Complutense Madrid, Spain.
authors.forename: M Dolores
authors.initials: MD
authors.lastname: Jiménez-Antón
authors.affiliation: National Microbiology Centre, Institute of Health Carlos III (ISCIII), Majadahonda, Madrid, Spain.
authors.forename: Laureano
authors.initials: L
authors.lastname: Cuevas
authors.affiliation: Department of Analytical Chemistry, Optical Chemosensors and Applied Photochemistry Group (GSOLFA), University Complutense Madrid, Spain.
authors.forename: María C
authors.initials: MC
authors.lastname: Moreno-Bondi
authors.affiliation: Department of Animal Health, Group ICPVet, Faculty of Veterinary Medicine, University Complutense Madrid, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Alunda
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D004220:Disulfides; D004305:Dose-Response Relationship, Drug; D007891:Leishmania / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000187:drug effects*; D017382:Reactive Oxygen Species; D013441:Sulfinic Acids / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D004220:Disulfides; D017382:Reactive Oxygen Species; D013441:Sulfinic Acids; C006452:allicin; D000255:Adenosine Triphosphate; D002118:Calcium