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Investigating the antifibrotic effect of the antiparasitic drug Praziquantel in in vitro and in vivo preclinical models.

Abstract：

:Tissue fibrosis underlies the majority of human mortality to date with close to half of all reported deaths having a fibrotic etiology. The progression of fibrosis is very complex and reputed irreversible once established. Although some preventive options are being reported, therapeutic options are still scarce and in very high demand, given the rise of diseases linked to fibroproliferative disorders. Our work explored four platforms, complementarily, in order to screen preventive and therapeutic potentials of the antiparasitic drug Praziquantel as a possible antifibrotic. We applied the mouse CCl4-driven liver fibrosis model, the mouse chronic schistosomiasis liver fibrosis model, as well as novel 2D and 3D human cell-based co-culture of human hepatocytes, KCs (Kupffer cells), LECs (Liver Endothelial Cells), HSCs (Hepatic Stellate Cells) and/or myofibroblasts to mimic in vivo fibrotic responses and dynamics. Praziquantel showed some effect on fibrosis marker when preventively administered before severe establishment of fibrosis. However, it failed to potently reverse already established fibrosis. Together, we provided a novel sophisticated multi-assay screening platform to test preventive and therapeutic antifibrotic candidates. We further demonstrated a direct preventive potential of Praziquantel against the onset of fibrosis and the confirmation of its lack of therapeutic potential in reversing already established fibrosis.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Nono JK,Fu K,Mpotje T,Varrone G,Aziz NA,Mosala P,Hlaka L,Kamdem SD,Xu D,Spangenberg T,Brombacher F

doi

10.1038/s41598-020-67514-4

subject

Has Abstract

pub_date

2020-06-30 00:00:00

pages

10638

issue

1

issn

2045-2322

pii

10.1038/s41598-020-67514-4

journal_volume

10

pub_type

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