title: Revealing praziquantel molecular targets using mass spectrometry imaging: an expeditious approach applied to Schistosoma mansoni.
abstract: Finding specific molecular targets and the mechanism of action of praziquantel in the treatment of schistosomiasis remains a challenging task. Our efforts were focused on obtaining further information on worm composition before and after exposure to praziquantel in the treatment of schistosomiasis to elucidate the potential sites of action of this drug. Evidence indicates that the lipid bilayer is changed by treatment with praziquantel. Following this rationale, we employed a mass spectrometry imaging-based approach that helped to characterise lipids in specific locations, which are directly involved in the biochemical pathways of the BH strain of Schistosoma mansoni, as well as differentiating the molecular response that each worm sex presents in vivo. Our findings demonstrated significant differences between the chemical markers found in adult worms before and after praziquantel exposure, especially in phospholipids, which were predominantly identified as chemical markers in all samples. Results also indicate that distinct molecular pathways in both male and female worms could be differentially affected by praziquantel treatment. These data shine new light on the mechanism of action of praziquantel, taking a further step towards its full understanding.
authors: Innovare Biomarkers Laboratory, Medicine and Experimental Surgery Nucleus, University of Campinas, Campinas, São Paulo, Brazil.
authors: Mônica Siqueira
authors: MS
authors: Ferreira
authors: Biology Institute, Animal Biology Department, University of Campinas, Campinas, São Paulo, Brazil.
authors: Rosimeire Nunes
authors: RN
authors: de Oliveira
authors: Innovare Biomarkers Laboratory, Medicine and Experimental Surgery Nucleus, University of Campinas, Campinas, São Paulo, Brazil.
authors: Diogo Noin
authors: DN
authors: de Oliveira
authors: Innovare Biomarkers Laboratory, Medicine and Experimental Surgery Nucleus, University of Campinas, Campinas, São Paulo, Brazil.
authors: Cibele Zanardi
authors: CZ
authors: Esteves
authors: Biology Institute, Animal Biology Department, University of Campinas, Campinas, São Paulo, Brazil. Electronic address: sallegre@unicamp.br.
authors: Silmara Marques
authors: SM
authors: Allegretti
authors: Innovare Biomarkers Laboratory, Medicine and Experimental Surgery Nucleus, University of Campinas, Campinas, São Paulo, Brazil. Electronic address: rrc@fcm.unicamp.br.
authors: Rodrigo Ramos
authors: RR
authors: Catharino
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D015415:Biomarkers; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D057054:Molecular Imaging / Q000379:methods*; D011223:Praziquantel / Q000494:pharmacology*; D012550:Schistosoma mansoni / Q000187:drug effects*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D000871:Anthelmintics; D015415:Biomarkers; D011223:Praziquantel
keywords: Biomarkers; Lipids; Mass spectrometry imaging; Praziquantel; Schistosoma mansoni