Gabexate mesilate, a synthetic protease inhibitor, attenuates carbon tetrachloride-induced liver injury in rats.
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.
Mikami
Ken-ichiro
K
Department of Gastroenterology, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
Goto
Takashi
T
Miura
Kouichi
K
Ohshima
Shigetoshi
S
Yoneyama
Kazuo
K
Lin
Jiun-Guey
JG
Watanabe
Daisuke
D
Segawa
Daisuke
D
Kataoka
Ei
E
Shibuya
Tomomi
T
Watanabe
Sumio
S
D000818:Animals; D002251:Carbon Tetrachloride / Q000008:administration & dosage / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury; D004195:Disease Models, Animal; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D016670:Gabexate / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000097:blood; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008107:Liver Diseases / Q000097:blood / Q000188:drug therapy*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D000637:Transaminases / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D015842:Serine Proteinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D016670:Gabexate; D002251:Carbon Tetrachloride; D000637:Transaminases