The influences of antihistamine on liver fibrosis, vasoresponsiveness, and portosystemic shunting in bile duct-ligated cirrhotic rats

초록

BACKGROUND: Liver cirrhosis with portal hypertension is a sequela of chronic hepatitis, characterized by liver fibrosis, poor portosystemic collateral vasoresponsiveness, increased mesenteric angiogenesis, and collateral formation. Antihistamines are frequently used to control pruritus in cirrhotic patients, and it has also been shown to reverse histamine-induced inflammation, fibrogenesis, angiogenesis, and vasodilatation. However, the relevant impacts on cirrhosis are not clear. METHODS: Liver cirrhosis was induced in rats with common bile duct ligation (BDL). Sham rats were surgical controls. Levocetirizine (0.5 mg/kg/day, oral gavage) or vehicle was administered from the 1st day after operations and experiments were performed on the 29th day to survey: (a) Systemic and splanchnic hemodynamic parameters; (b) serum liver and renal biochemistry parameters; (c) protein expressions of liver fibrogenesis factors; (d) portosystemic collateral vasoresponsiveness to vasopressin; (e) portosystemic shunting degree; and (f) mesenteric angiogenesis. RESULTS: Compared with the vehicle, levocetirizine decreased portal pressure, superior mesenteric artery flow, portal vein (PV) flow, and elevated PV resistance in BDL rats. Levocetirizine significantly down-regulated the hepatic TGF-β, p-Smad2, MMP-2, and TIMP-1 protein expressions in BDL rats. Levocetirizine did not affect the collateral vasoresponsiveness to vasopressin but tended to reduce the severity of portosystemic shunting and mesenteric angiogenesis. CONCLUSION: Levocetirizine ameliorated liver fibrosis, portal hypertension, and splanchnic hyperdynamic circulation in cirrhotic rats, possibly through the downregulation of hepatic fibrogenesis factors. Antihistamines may be a therapeutic option to control portal hypertension. However, further investigations are required to clarify its clinical application.

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