Zaneta Kidiavai (Berlin / DE), Arkadi Kundik (Berlin / DE), Dr. Jürgen Krücken (Berlin / DE), Univ.-Prof. Dr. rer. nat. Susanne Hartmann (Berlin / DE)
Abstract text
Soil transmitted helminths (STH) infect a total of 807 million – 1.2 billion people in the world, Ascaris lumbricoidesbeing the most prevalent gut nematode in sub-Saharan Africa. Important to note is that co-infection with malaria, caused by Plasmodium falciparum, and STH is common in areas with overlapping endemicity. WHO recommends the use of artemisinin-based combination therapy (ACTs) as the first-line treatment of symptomatic malaria.
Artemisinin and its derivatives; artemether, artesunate and dihydroartemisinin (ARTs), have pharmacological activity not only against Plasmodium falciparum but also helminths i.e., schistosome spp., viruses i.e., SARs Cov-2, cancers like lung carcinoma and autoimmune diseases i.e., inflammatory bowel syndrome. Our study aims to investigate the in vitro antinematode activity of artemisinin, artesunate and artemether on the energy metabolism of A. suum L3.
A. suum L3 were exposed to artemisinin, artesunate or artemether for 24 hours and evaluated for general metabolic activity or ATP production using the resazurin assay or bioluminescence ATP assay respectively. We detect a dose dependent inhibition by artesunate and artemether on the metabolic activity of A. suum L3. Thus, the derivatives, artemether and artesunate, were more effective when compared to artemisinin. Resazurin has been reported to detect mitochondrial function, therefore, a potential mechanism of action of artesunate and artemether could be an interference with the electron transport chain of the mitochondria. Consequently, fluorescence lifetime imaging microscopy is used in current experiments to further investigate metabolic enzymes affected in artesunate and artemether exposed A. suum L3. Thus far, our data indicate that ARTs may have a direct inhibitory effect on the nematode metabolism.