The Effect of Terguride in Carbon Tetrachloride–Induced Liver Fibrosis in Rat

Abstract

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. 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. 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. 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. Terguride, a potent 5-HT(2) antagonist, did not prevent the development of liver fibrosis in rats given CCL(4).