RGD Reference Report - Gabexate mesilate, a synthetic protease inhibitor, attenuates carbon tetrachloride-induced liver injury in rats. - Rat Genome Database

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Gabexate mesilate, a synthetic protease inhibitor, attenuates carbon tetrachloride-induced liver injury in rats.

Authors: Mikami, K  Goto, T  Miura, K  Ohshima, S  Yoneyama, K  Lin, JG  Watanabe, D  Segawa, D  Kataoka, E  Shibuya, T  Watanabe, S 
Citation: Mikami K, etal., J Gastroenterol. 2005 Mar;40(3):260-5.
RGD ID: 10450531
Pubmed: PMID:15830285   (View Abstract at PubMed)
DOI: DOI:10.1007/s00535-004-1534-3   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Chemical and Drug Induced Liver Injury treatmentISOTnf (Rattus norvegicus)10450531; 10450531 RGD 
Chemical and Drug Induced Liver Injury treatmentIDA 10450531 RGD 

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
gabexate methanesulfonate decreases expression ISOTnf (Rattus norvegicus)10450531; 10450531gabexate mesilate decreases expression of Tnf protein in serumRGD 
gabexate methanesulfonate decreases expression EXP 10450531gabexate mesilate decreases expression of Tnf protein in serumRGD 

Objects Annotated

Genes (Rattus norvegicus)
Tnf  (tumor necrosis factor)

Genes (Mus musculus)
Tnf  (tumor necrosis factor)

Genes (Homo sapiens)
TNF  (tumor necrosis factor)


Additional Information