Format

Send to

Choose Destination
Front Cell Infect Microbiol. 2018 Jul 26;8:256. doi: 10.3389/fcimb.2018.00256. eCollection 2018.

Artemisinin Derivatives and Synthetic Trioxane Trigger Apoptotic Cell Death in Asexual Stages of Plasmodium.

Author information

1
Academy of Scientific and Innovative Research, New Delhi, India.
2
Division of Parasitology, Central Drug Research Institute (CDRI), Council of Scientific and Industrial Research (CSIR), Lucknow, India.
3
Division of Molecular & Structural Biology, Central Drug Research Institute (CDRI), Council of Scientific and Industrial Research (CSIR), Lucknow, India.

Abstract

Although over the last 15 years, prevalence of malaria became reduced by over half but developing resistance against artemisinin derivatives and its combinations, which are only ray of hope to treat resistant malaria set back the control efforts and the key hinderence to achieve the goal of malaria elimination till 2030. In spite these artemisinins are precious antimalarials, their action mechanism is yet to be fully understood. Reactive oxygen species (ROS) produces by cleavage of endoperoxide bridge of artemisinin derivatives are known to be its antimalarial efficacy. Since ROS could induce apoptosis, here we had explored the effect of artemisinin derivatives on apoptotic machinery of malaria parasite, Plasmodium falciparum and its survival. We have studied the effect of a/β arteether, artesunate and a synthetic 1, 2, 4 trioxane on mitochondria, caspase activity and DNA during asexual blood stages of Plasmodium falciparum 3D7. Results have shown that cleavage of peroxide bridge of artemisinin derivatives and 1,2,4 trioxane generate reactive oxygen species which depolarize mitochondrial membrane potential and make it permeable which further followed by activation of caspase like enzyme and DNA fragmentation, which are hallmark of apoptotic cell death. These findings suggest that artemisinin derivatives and synthetic trioxane induce apoptosis like phenomena in erythrocytic stage of malaria parasite; Plasmodium falciparum.

KEYWORDS:

CDRI-97/78; Plasmodium; apoptosis; arteether; artesunate

PMID:
30094226
PMCID:
PMC6070741
DOI:
10.3389/fcimb.2018.00256
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center