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.
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.
Authors: Ivana Nikolic; Lai-Ming Yung; Peiran Yang; Rajeev Malhotra; Samuel D Paskin-Flerlage; Teresa Dinter; Geoffrey A Bocobo; Kathleen E Tumelty; Anthony J Faugno; Luca Troncone; Megan E McNeil; Xiuli Huang; Kathryn R Coser; Carol S C Lai; Paul D Upton; Marie Jose Goumans; Roham T Zamanian; C Gregory Elliott; Arthur Lee; Wei Zheng; Stephen P Berasi; Christine Huard; Nicholas W Morrell; Raymond T Chung; Richard W Channick; Kari E Roberts; Paul B Yu Journal: Am J Respir Crit Care Med Date: 2019-04-01 Impact factor: 21.405