Continuous hepatocyte growth factor supply prevents lipopolysaccharide-induced liver injury in rats.
We present a rat model in which continuous supply of hepatocyte growth factor (HGF) prevents liver injury induced by carbon tetrachloride (CCl4) and E. coli 011:B4 lipopolysaccharide (LPS). Rat fibroblasts genetically modified to secrete rat HGF were implanted in syngenic rat spleen 7 days before administration of the hepatotoxins. Rats with HGF-secreting fibroblasts in the spleen showed a dramatic resistance to CCl4- and LPS-induced liver injury. In the LPS-induced liver injury model, blood chemical analysis revealed that the increase in serum glutamic oxalacetic transaminase level and the decrease in blood sugar level were remarkably suppressed in rats with HGF-secreting cells in the spleen. Most importantly, their survival rate was greatly improved compared to other control groups of rats. Thus our results indicate a new role of HGF in liver protection during endotoxemia and convey important clinical implications for developing new therapeutic modalities in the treatment of liver failure caused by endotoxemia.
Kaido
T
T
Department of Surgery and Surgical Basic Science, Kyoto University School of Medicine, Japan.
Yamaoka
S
S
Seto
S
S
Funaki
N
N
Kasamatsu
T
T
Tanaka
J
J
Nakamura
T
T
Imamura
M
M
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000633:toxicity*; D017690:Cell Transplantation; D019446:Endotoxemia / Q000188:drug therapy; D004731:Endotoxins / Q000633:toxicity; D005347:Fibroblasts; D017228:Hepatocyte Growth Factor / Q000097:blood / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000378:metabolism; D013154:Spleen / Q000378:metabolism
D004731:Endotoxins; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; C044101:endotoxin, Escherichia coli; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase