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

Abstract

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-hydroxytryptamine₂ (5-HT₂, serotonin) receptor antagonists upon HSCs. Terguride, recognized as a partial dopamine agonist, also has potent 5-HT₂ receptor antagonist qualities and has been shown to prevent serotonin-induced organ changes and fibrosis in rats. Aim: In the current study, the carbon tetrachloride (CCL₄) hepatic fibrosis rat model was used in combination with daily administration of terguride to evaluate potential preventive effects of a 5-HT₂ receptor antagonist upon liver fibrosis. Materials and Methods: Forty rats (Sprague-Dawley) were included in the study. Twelve animals received terguride in combination with CCL₄ and 12 animals were given only CCL₄. The remaining 16 animals served as model controls. The extent of fibrosis was evaluated by liver weight, histologic analysis, biochemical analysis, and α-smooth muscle actin (α-SMA) immunohistochemistry. Results: There were no significant differences in liver weight, hydroxyproline content, serum alanine and aspartate transaminases, serum hyaluronic acid, or α-SMA immunostaining between rats treated with terguride in combination with CCL₄ and rats given only CCL₄. All parameters, however, were significantly lower (P < 0.01) in the model controls. Conclusion: Terguride, a potent 5-HT₂ antagonist, did not prevent the development of liver fibrosis in rats given CCL₄.

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