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Gabexate mesilate, a synthetic protease inhibitor, attenuates carbon tetrachloride-induced liver injury in rats
- Source :
- Journal of Gastroenterology. 40:260-265
- Publication Year :
- 2005
- Publisher :
- Springer Science and Business Media LLC, 2005.
-
Abstract
- 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.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.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%.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.
- Subjects :
- Male
Proteases
Serine Proteinase Inhibitors
Gabexate
Enzyme-Linked Immunosorbent Assay
CCL4
Pharmacology
Lethal Dose 50
Rats, Sprague-Dawley
chemistry.chemical_compound
medicine
Animals
Protease inhibitor (pharmacology)
Carbon Tetrachloride
Transaminases
Disseminated intravascular coagulation
Liver injury
Tumor Necrosis Factor-alpha
Chemistry
Liver Diseases
Gastroenterology
medicine.disease
Rats
Disease Models, Animal
Liver
Immunology
Disease Progression
Carbon tetrachloride
Acute pancreatitis
Tumor necrosis factor alpha
Chemical and Drug Induced Liver Injury
Interleukin-1
Subjects
Details
- ISSN :
- 14355922 and 09441174
- Volume :
- 40
- Database :
- OpenAIRE
- Journal :
- Journal of Gastroenterology
- Accession number :
- edsair.doi.dedup.....f9e44d1fdb5ed7b3780c3fb0af1e1ffd