Effect of fibrin glue occlusion of the hepatobiliary tract on thioacetamide-induced liver failure.
BACKGROUND
Expression and activation of hepatocyte growth factor (HGF) is stimulated by a complex system of interacting proteins, with thrombin playing an initial role in this process. The impact of temporary occlusion of the hepatobiliary tract with fibrin glue (major component thrombin) on the HGF system in acute and chronic liver damage in a rat model was investigated.


METHODS
Chronic liver damage was induced in 40 rats by daily intraperitoneal application of thioacetamide (100 mg/kg) for 14 days. After 7 days half of them received an injection of 0.2 mL fibrin glue into the hepatobiliary system. Daily intraperitoneal administration of thioacetamide continued for 7 consecutive days. The rats were then sacrificed for blood and tissue analysis. Acute liver failure was induced in 12 rats by intraperitoneal administration of a lethal dose of thioacetamide (500 mg/kg per day for 3 days) after an injection with 0.2 mL fibrin glue into their hepatobiliary tract. Survival rates and histological outcome were investigated and compared with control animals.


RESULTS
Fibrin glue occluded rats showed significantly lower liver enzyme activities and serum levels of bilirubin, creatinine and urea nitrogen. Immunohistochemistry revealed a significant increase in c-met-, HGFalpha- and especially HGFbeta-positive cells. Rats subjected to a lethal dose of thioacetamide survived when fibrin glue was applied 24 hours prior to the toxic challenge. These animals showed normal liver structure and no clinical abnormalities.


CONCLUSIONS
Fibrin glue occlusion of the hepatobiliary tract induces therapeutic and prophylactic effects on chronic and acute liver failure by stimulating the HGF system. Therefore, fibrin glue occlusion might be useful in treating toxic liver failure.
Schmandra
T C
TC
Department of Surgery, Johann Wolfgang Goethe-University Hospital, Theodor Stern Kai 7, 60590, Frankfurt am Main, Germany.
Bauer
H
H
Petrowsky
H
H
Herrmann
G
G
Encke
A
A
Hanisch
E
E
D000818:Animals; D015718:Fibrin Tissue Adhesive / Q000008:administration & dosage*; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008099:Liver / Q000378:metabolism / Q000473:pathology; D017093:Liver Failure / Q000139:chemically induced / Q000628:therapy*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000628:therapy; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D013853:Thioacetamide / Q000506:poisoning; D014014:Tissue Adhesives / Q000008:administration & dosage*
D015718:Fibrin Tissue Adhesive; D014014:Tissue Adhesives; D013853:Thioacetamide; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met