Thiazolidinedione treatment inhibits bile duct proliferation and fibrosis in a rat model of chronic cholestasis.
OBJECTIVE
To investigate the effects of troglitazone (TGZ), an anti-diabetic drug which activates peroxisome proliferator-activated receptor-gamma (PPAR-gamma), for liver tissue repair, and the development of ductular reaction, following common bile duct ligation (BDL) in rats.


METHODS
Rats were supplemented with TGZ (0.2% w/w in the pelleted food) for 1 wk before BDL or sham operation. Animals were killed at 1, 2, or 4 wk after surgery.


RESULTS
The development of liver fibrosis was reduced in rats receiving TGZ, as indicated by significant decreases of procollagen type I gene expression and liver hydroxy-proline levels. Accumulation of alpha-smooth-muscle actin (SMA)-expressing cells surrounding newly formed bile ducts following BDL, as well as total hepatic levels of SMA were partially inhibited by TGZ treatment, indicating the presence of a reduced number and/or activation of hepatic stellate cells (HSC) and myofibroblasts. Development of the ductular reaction was inhibited by TGZ, as indicated by histochemical evaluation and hepatic activity of gamma-glutamyl-transferase (GGT).


CONCLUSIONS
Treatment with thiazolidinedione reduces ductular proliferation and fibrosis in a model of chronic cholestasis, and suggests that limiting cholangiocyte proliferation may contribute to the lower development of scarring in this system.
Marra
Fabio
F
Dipartimento di Medicina Interna, University of Florence, Viale Morgagni 85, Florence I-50134, Italy. f.marra@dmi.unifi.it
DeFranco
Raffaella
R
Robino
Gaia
G
Novo
Erica
E
Efsen
Eva
E
Pastacaldi
Sabrina
S
Zamara
Elena
E
Vercelli
Alessandro
A
Lottini
Benedetta
B
Spirli
Carlo
C
Strazzabosco
Mario
M
Pinzani
Massimo
M
Parola
Maurizio
M
D000818:Animals; D001652:Bile Ducts / Q000187:drug effects / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002779:Cholestasis / Q000188:drug therapy* / Q000473:pathology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione