Journal article

Publication year: 2022

Pages: 1145-1153

Journal: Parasitology Research

Volume number: 121

Issue number: 4

ISSN: 0932-0113

eISSN: 1432-1955

Open access status: Hybrid

DOI Link: https://doi.org/10.1007/s00436-021-07388-1

Publisher: Springer

Abstract: 
Understanding drug penetration, distribution, and metabolization is fundamental for understanding drug efficacy. This also accounts for parasites during antiparasitic treatment. Recently, we established matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) in blood flukes and liver flukes. This label-free technique is capable of visualizing the molecular distribution of endogenous and exogenous molecules, such as drug compounds. Here, we conducted atmospheric-pressure scanning microprobe MALDI MSI (AP-SMALDI MSI) of tissue sections of adult Fasciola hepatica that have been treated in vitro with 100 mu M of triclabendazole (TCBZ), the drug of choice for treatment of fasciolosis, and its main metabolite triclabendazole sulfoxide (TCBZ-SO). Measurements covered an m/z mass range of 250-1,000 and provided a high spatial resolution using a pixel size of 10 mu m. To support the interpretation of drug distribution, we first identified endogenous lipids that mark characteristic tissues such as the gastrodermis, the tegument, and the parenchyma. The obtained results suggested an early tegumental route of TCBZ uptake within 20 min, followed by spreading throughout the parasite after 4 h, and an even distribution in most tissues after 12 h. This coincided with a strong reduction of parasite vitality. TCBZ-SO treatment demonstrated the accumulation of this metabolite in the same tissues as the parent drug compound. These data demonstrate the auspicious potential of MALDI MSI to visualize uptake and distribution patterns of drugs or drug-candidate compounds in parasites, which might contribute to preclinical drug discovery in liver fluke research and beyond.

Harvard Citation style: Morawietz, C., Ventura, A., Grevelding, C., Haeberlein, S. and Spengler, B. (2022) Spatial visualization of drug uptake and distribution in Fasciola hepatica using high-resolution AP-SMALDI mass spectrometry imaging, Parasitology Research, 121(4), pp. 1145-1153. https://doi.org/10.1007/s00436-021-07388-1

APA Citation style: Morawietz, C., Ventura, A., Grevelding, C., Haeberlein, S., & Spengler, B. (2022). Spatial visualization of drug uptake and distribution in Fasciola hepatica using high-resolution AP-SMALDI mass spectrometry imaging. Parasitology Research. 121(4), 1145-1153. https://doi.org/10.1007/s00436-021-07388-1