Evaluation of Human Liver Microtissues for Drug Screening on <i>Schistosoma mansoni</i> Schistosomula.

ABSTRACT: Schistosomiasis is a major neglected tropical disease with more than 200 million infections annually. Despite only one drug, praziquantel, being available, the drug pipeline against schistosomiasis is empty, and drug screening tools have limitations. We evaluated the potential of human liver microtissues (hLiMTs) in antischistosomal drug discovery. Because hLiMTs express all human P450 enzymes, they are an excellent tool to evaluate compounds' bioinactivation, bioactivation, and toxicity. To validate the metabolic conversion capacity of hLiMTs, we first quantified (R)- and (S)-praziquantel and the main metabolite trans-OH-praziquantel following incubation with 0.032-50 μM (0.01-15.62 μg/mL) praziquantel for up to 72 h by a validated LC-MS/MS method. We cocultured hLiMT

SUBMITTER: Lombardo FC 

PROVIDER: S-EPMC7611177 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature