Preventive effects of the deleted form of hepatocyte growth factor against various liver injuries.
The effects of a naturally occurring deleted form of hepatocyte growth factor (HGF) on hepatic disorder were studied in various models of hepatic failure. The pretreatment of rats and mice with the deleted form of HGF prevented the liver injuries and coagulopathy induced by endotoxin, dimethylnitrosamine and acetaminophen and reduced the mortality due to hepatic dysfunction induced by these hepatotoxins. The concurrent administration of the deleted form of HGF also prevented the liver injury and hepatic fibrosis in mice treated with alpha-naphthylisothiocyanate and in rats treated with dimethylnitrosamine. Moreover, the deleted form of HGF normalized the results of the bromosulphalein-clearance test and ameliorated jaundice in rats with periportal cholangiolitic hepatopathy induced by alpha-naphthylisothiocyanate. The deleted form of HGF also reversed the coagulopathy in rats with hepatic disorder induced by dimethylnitrosamine or by 70% resection of cirrhotic liver (induced by carbon tetrachloride). In Long Evans cinnamon rats receiving vehicle, 20 out of 21 animals died within 4 days after the onset of jaundice. After infusion of the deleted form of HGF for 4 days, 7 out of 20 Long-Evans cinnamon rats survived. These results indicate that the deleted form of HGF could have therapeutic potency in patients with severe hepatic failure.
Masunaga
H
H
Life Science Research Institute, Snow Brand Milk Products Co. Ltd., Tochigi, Japan.
Fujise
N
N
Shiota
A
A
Ogawa
H
H
Sato
Y
Y
Imai
E
E
Yasuda
H
H
Higashio
K
K
D000818:Animals; D001778:Blood Coagulation Disorders / Q000139:chemically induced / Q000209:etiology; D056486:Chemical and Drug Induced Liver Injury / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D004731:Endotoxins / Q000633:toxicity; D005260:Female; D005355:Fibrosis / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D008099:Liver / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000473:pathology / Q000517:prevention & control; D017114:Liver Failure, Acute / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D051381:Rats; D017208:Rats, Wistar
D004731:Endotoxins; D017228:Hepatocyte Growth Factor