Reduction of monocrotaline-induced hepatic injury by deleted variant of hepatocyte growth factor (dHGF) in rats.
BACKGROUND
Monocrotaline is a hepatotoxic agent which exerts predominant toxicity to central veins and centrilobular sinusoids. In this study, we investigated the effects of deleted variant of hepatocyte growth factor (dHGF) on monocrotaline-induced hepatic injury in rats.


METHODS
100 mg/kg monocrotaline was gavaged to male rats twice with a 4-days' interval. Treatment of dHGF was started 4 days before the initial administration of monocrotaline and 500 microg/kg was intravenously injected twice daily for 11 days.


RESULTS
Monocrotaline induced severe damage of central veins and destruction of central zone of hepatic lobules concurrent with derangement of blood levels of total protein, albumin, alanine-aminotransferase, total bilirubin, direct bilirubin, and hepaplastin time. dHGF reduced the structural and blood-chemical abnormalities induced by monocrotaline.


CONCLUSIONS
These results suggest that dHGF prevented and repaired the monocrotaline-induced hepatic injury, and could have therapeutic potency in hepatic failure with sever centrilobular destruction.
Yamashita
Yasushi
Y
Research Institute of Life Science, Snow Brand Milk Products, Co, Ltd, Tochigi, Japan. yyas@mug.viglobe.ne.jp
Fujise
Nobuaki
N
Imai
Eiichi
E
Masunaga
Hiroaki
H
D000284:Administration, Oral; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control*; D019963:Clinical Chemistry Tests; D017228:Hepatocyte Growth Factor / Q000627:therapeutic use*; D008297:Male; D016686:Monocrotaline / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D020033:Protein Isoforms; D051381:Rats; D017207:Rats, Sprague-Dawley
D020033:Protein Isoforms; D017228:Hepatocyte Growth Factor; D016686:Monocrotaline