Insulin-like growth factor-I prevents lethal acute liver failure induced by D-galactosamine and lipopolysaccharide in rats.
The aim of this study was to evaluate the effect of insulin-like growth factor-I (IGF-I) on lethality and liver function in experimental acute liver failure. Intravenous co-administration of D-galactosamine (GalN) and lipopolysaccharide (LPS) to rats induced high mortality and marked increases in aspartate aminotransferase, alanine aminotransferase and total bilirubin, associated with hypoglycemia. One-hour pre-treatment with IGF-I significantly prevented lethality and blood parameter changes in rats. Histological examination also showed that massive hepatocellular hemorrhagic necrosis and inflammatory cell infiltration around peri-central veins in the liver, as well as shrinkage of cytoplasm and nuclear condensation, were induced by GalN plus LPS injection, but these all were improved by pre-treatment with IGF-I. Overall, this study showed that IGF-I treatment resulted in effective prevention of lethal acute liver failure in rats induced by GalN plus LPS, suggesting a therapeutic potential for IGF-I in the prevention of acute liver failure.
Inoue
Takeshi
T
Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 2-1-6, Kashima, Yodogawa-ku, Osaka 532-8514, Japan.
Horiai
Haruo
H
Aoki
Chizuru
C
Kawamura
Ikuo
I
Ota
Mariko
M
Mizuhara
Hidekazu
H
Tomoi
Masaaki
M
Mutoh
Seitaro
S
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D004195:Disease Models, Animal; D005688:Galactosamine / Q000008:administration & dosage / Q000633:toxicity*; D006801:Humans; D007275:Injections, Intravenous; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D017114:Liver Failure, Acute / Q000139:chemically induced* / Q000473:pathology* / Q000517:prevention & control*; D051381:Rats; D011994:Recombinant Proteins / Q000627:therapeutic use
D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D005688:Galactosamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin