The effect of terguride in carbon tetrachloride-induced liver fibrosis in rat.
BACKGROUND
Hepatic stellate cells (HSCs) are considered to be of vital importance in the pathogenesis of liver fibrosis. In vitro studies have demonstrated antiproliferative effects of 5-hydroxytryptamine(2) (5-HT(2), serotonin) receptor antagonists upon HSCs. Terguride, recognized as a partial dopamine agonist, also has potent 5-HT(2) receptor antagonist qualities and has been shown to prevent serotonin-induced organ changes and fibrosis in rats.


OBJECTIVE
In the current study, the carbon tetrachloride (CCL(4)) hepatic fibrosis rat model was used in combination with daily administration of terguride to evaluate potential preventive effects of a 5-HT(2) receptor antagonist upon liver fibrosis.


METHODS
Forty rats (Sprague-Dawley) were included in the study. Twelve animals received terguride in combination with CCL(4) and 12 animals were given only CCL(4). The remaining 16 animals served as model controls. The extent of fibrosis was evaluated by liver weight, histologic analysis, biochemical analysis, and alpha-smooth muscle actin (alpha-SMA) immunohistochemistry.


RESULTS
There were no significant differences in liver weight, hydroxyproline content, serum alanine and aspartate transaminases, serum hyaluronic acid, or alpha-SMA immunostaining between rats treated with terguride in combination with CCL(4) and rats given only CCL(4). All parameters, however, were significantly lower (P < 0.01) in the model controls.


CONCLUSIONS
Terguride, a potent 5-HT(2) antagonist, did not prevent the development of liver fibrosis in rats given CCL(4).
Hauso
Oyvind
O
Department of Cancer Research and Molecular Medicine, NTNU, MTFS, N-7489, Trondheim, Norway. oyvind.hauso@ntnu.no
Gustafsson
Björn I
BI
Nordrum
Ivar S
IS
Waldum
Helge L
HL
D000199:Actins / Q000032:analysis; D000818:Animals; D001774:Blood Chemical Analysis; D002251:Carbon Tetrachloride; D005260:Female; D007150:Immunohistochemistry; D008090:Lisuride / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use*
D000199:Actins; D002251:Carbon Tetrachloride; D008090:Lisuride; D012702:Serotonin Antagonists; C498862:Acta2 protein, rat; C006208:dironyl