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Keywords:

  • gabexate mesilate;
  • hepatic encephalopathy;
  • hepatic failure

Abstract

Background and Aim: Inflammation plays a pivotal role in liver injury. Gabexate mesilate (GM, a protease inhibitor) inhibits inflammation by blocking various serine proteases. This study examined the effects of GM on hepatic encephalopathy in rats with acute and chronic liver failure.

Methods: Acute and chronic liver failure (cirrhosis) were induced by intraperitoneal TAA administration (350 mg/kg/day for 3 days) and common bile duct ligation in male Sprague-Dawley rats, respectively. Rats were randomized to receive either GM (50 mg/10ml/kg) or saline intraperitoneally for 5 days. Severity of encephalopathy was assessed by the Opto-Varimex animal activity meter and hemodynamic parameters, mean arterial pressure and portal pressure, were measured (only chronic liver failure rats). Plasma levels of liver biochemistry, ammonia, nitrate/nitrite, interleukins (IL) and tumor necrosis factor (TNF)-α were determined.

Results: In rats with acute liver failure, GM treatment significantly decreased the plasma levels of alanine aminotransferase (p = 0.02), but no significant difference of motor activity, plasma levels of ammonia, IL-1β, IL-6, IL-10 and TNF-α or survival was found. In chronic liver failure rats, GM significantly lowered the plasma TNF-α levels (p = 0.04). However, there was no significant difference of motor activity, other biochemical tests or survival found. GM-treated chronic liver failure rats had higher portal pressure (p = 0.04) but similar mean arterial pressure in comparison with saline-treated rats.

Conclusions: Chronic GM treatment does not have a major effect on hepatic encephalopathy in rats with TAA-induced acute liver failure and rats with chronic liver failure induced by common bile duct ligation.