Continuous intravenous infusion of deleted form of hepatocyte growth factor attenuates hepatic ischemia-reperfusion injury in rats.
OBJECTIVE
Although beneficial roles of hepatocyte growth factor (HGF) and its variants on several hepatic disorders have been reported, their effects on hepatic ischemia-reperfusion (IR) injury remain undetermined. We investigated the action of a deleted form of HGF (dHGF) on hepatic IR injury in rats.


METHODS
dHGF or phosphate-buffered saline was continuously infused intravenously for 20 h prior to a 20-min occlusion of hepatic vessels. Samples were taken before and after IR, for measurement of serum dHGF and released enzymes, liver gamma-glutamylcysteinyl glycine (GSH) level, as well as histological and immunohistochemical examinations.


RESULTS
After reperfusion, histological injury, as well as increase in the serum activities of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and creatine kinase-BB were significantly attenuated in the dHGF-treated rats. dHGF maintained a high GSH level and suppressed oxidative stress and intercellular adhesion molecule-1 (ICAM-1) expression on sinusoidal endothelial cells (SECs), on which c-Met was not detected. IR caused activation of c-Met expression, which was milder in the dHGF-treated group, in hepatocytes at the pericentral region.


CONCLUSIONS
dHGF attenuated liver injury after IR. It also maintained a higher GSH level, depressed oxidative stress and inhibited ICAM-1 expression on c-Met negative SECs, suggesting a paracrine effect of dHGF.
Oe
S
S
Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine, Japan. oes@kuhp.kyoto-u.ac.jp
Hiros
T
T
Fujii
H
H
Yasuchika
K
K
Nishio
T
T
Iimuro
Y
Y
Morimoto
T
T
Nagao
M
M
Yamaoka
Y
Y
D000080242:8-Hydroxy-2'-Deoxyguanosine; D017398:Alternative Splicing; D000818:Animals; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007262:Infusions, Intravenous; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000293:injuries*; D008297:Male; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000235:genetics; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D017384:Sequence Deletion
D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D017228:Hepatocyte Growth Factor; D000080242:8-Hydroxy-2'-Deoxyguanosine; D019859:Proto-Oncogene Proteins c-met; D003849:Deoxyguanosine; D005978:Glutathione