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2018 ; 2
(7
): 821-835
Nephropedia Template TP
gab.com Text
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English Wikipedia
Molecular magnetic resonance imaging accurately measures the antifibrotic effect
of EDP-305, a novel farnesoid X receptor agonist
#MMPMID30027140
Erstad DJ
; Farrar CT
; Ghoshal S
; Masia R
; Ferreira DS
; Chen YI
; Choi JK
; Wei L
; Waghorn PA
; Rotile NJ
; Tu C
; Graham-O'Regan KA
; Sojoodi M
; Li S
; Li Y
; Wang G
; Corey KE
; Or YS
; Jiang L
; Tanabe KK
; Caravan P
; Fuchs BC
Hepatol Commun
2018[Jul]; 2
(7
): 821-835
PMID30027140
show ga
We examined a novel farnesoid X receptor agonist, EDP-305, for its antifibrotic
effect in bile duct ligation (BDL) and choline-deficient, L-amino acid-defined,
high-fat diet (CDAHFD) models of hepatic injury. We used molecular magnetic
resonance imaging with the type 1 collagen-binding probe EP-3533 and the oxidized
collagen-specific probe gadolinium hydrazide to noninvasively measure treatment
response. BDL rats (n = 8 for each group) were treated with either low or high
doses of EDP-305 starting on day 4 after BDL and were imaged on day 18. CDAHFD
mice (n = 8 for each group) were treated starting at 6 weeks after the diet and
were imaged at 12 weeks. Liver tissue was subjected to pathologic and
morphometric scoring of fibrosis, hydroxyproline quantitation, and determination
of fibrogenic messenger RNA expression. High-dose EDP-305 (30 mg/kg) reduced
liver fibrosis in both the BDL and CDAHFD models as measured by collagen
proportional area, hydroxyproline analysis, and fibrogenic gene expression (all P
< 0.05). Magnetic resonance signal intensity with both EP-3533 in the BDL model
and gadolinium hydrazide in the CDAHFD model was reduced with EDP-305 30 mg/kg
treatment (P < 0.01). Histologically, EDP-305 30 mg/kg halted fibrosis
progression in the CDAHFD model. Conclusion: EDP-305 reduced fibrosis progression
in rat BDL and mouse CDAHFD models. Molecular imaging of collagen and oxidized
collagen is sensitive to changes in fibrosis and could be used to noninvasively
measure treatment response in clinical trials. (Hepatology Communications
2018;2:821-835).