Background: Gabexate mesilate, a synthetic protease inhibitor, is used to treat acute pancreatitis and disseminated intravascular coagulation because it inhibits various serine proteases; however, whether gabexate mesilate prevents acute liver failure has not yet been studied. The aim of the present study was to investigate the effect of gabexate mesilate in carbon tetrachloride (CCl4)-induced liver injury in rats.
Methods: Acute hepatic failure was induced by administration of CCl4 intragastrically to male Sprague-Dawley rats. The effects of gabexate mesilate were examined in terms of serum transaminase levels, liver histology, and the prognosis of rats.
Results: Gabexate mesilate treatment significantly decreased the elevation of serum transaminase levels and improved liver histology 24 h after the administration of CCl4 (0.2 ml/100 g rat weight). Plasma tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) decreased significantly in the gabexate mesilate-treated rats compared with saline-treated rats. Gabexate mesilate treatment also significantly improved survival rate after a lethal dose of CCl4 (0.5 ml/100 g rat weight) from 0% to 20%.
Conclusions: Gabexate mesilate treatment attenuated CCl4-induced liver injury via a suppression of proinflammatory cytokine production. In addition, these investigations suggest that gabexate mesilate treatment may provide therapeutic strategies for human acute liver failure.