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Gewählte Publikation:

Publikationstyp: Zeitschriftenaufsatz
Dokumentart: Originalarbeit

Publikationsjahr: 2019

AutorInnen: De Sarkar, S; Sarkar, D; Sarkar, A; Dighal, A; Chakrabarti, S; Staniek, K; Gille, L; Chatterjee, M

Titel: The leishmanicidal activity of artemisinin is mediated by cleavage of the endoperoxide bridge and mitochondrial dysfunction.

Quelle: Parasitology. 2019; 146(4):511-520

Autor/innen der Vetmeduni Vienna:

Gille Lars,
Staniek Katrin,

Beteiligte Vetmed-Organisationseinheiten
Institut für Pharmakologie und Toxikologie,

Zugehörige(s) Projekt(e): Auslöser und Angriffspunkte der Ascaridol-Wirkung in Leishmanien

Endoperoxides kill malaria parasites via cleavage of their endoperoxide bridge by haem or iron, leading to generation of cytotoxic oxygen-centred radicals. In view of the Leishmania parasites having a relatively compromised anti-oxidant defense and high iron content, this study aims to establish the underlying mechanism(s) accounting for the apoptotic-like death of Leishmania promastigotes by artemisinin, an endoperoxide. The formation of reactive oxygen species was confirmed by flow cytometry and was accompanied by inhibition of mitochondrial complexes I-III and II-III. However, this did not translate into a generation of mitochondrial superoxide or decrease in oxygen consumption, indicating minimal impairment of the electron transport chain. Artemisinin caused depolarization of the mitochondrial membrane along with a substantial depletion of adenosine triphosphatase (ATP), but it was not accompanied by enhancement of ATP hydrolysis. Collectively, the endoperoxide-mediated radical formation by artemisinin in Leishmania promastigotes was the key step for triggering its antileishmanial activity, leading secondarily to mitochondrial dysfunction indicating that endoperoxides represent a promising therapeutic strategy against Leishmania worthy of pharmacological consideration.

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