Impairment of Activation of Hepatocyte Growth Factor Precursor into Its Mature Form in Rats with Liver Cirrhosis

Defining Post Hepatectomy Liver Insufficiency: Where do We stand?

“…Animal models have demonstrated that after resection, cirrhosis is associated with decreased levels of hepatocyte growth factor, 30 impaired transcription factors, 31 and a reduction of DNA synthesis, leading to lower volumes of regenerated liver. 32 Largely due to the risk of PHLF, mortality following liver resection has traditionally been associated with a high mortality, reaching 30 % in some series.…”

Administration of rhHGF-Activator Via Portal Vein Stimulates the Regeneration of Cirrhotic Liver After Partial Hepatectomy in Rats1

“…Further, we found that the conversion of pro-HGF to its mature form was impaired in rats with cirrhotic liver after liver resection but that cirrhotic liver produced similar levels of proHGF to those in normal liver [18]. Accordingly, we were prompted to investigate whether the administration of rhHGFactivator stimulates the conversion of proHGF to mature form after liver resection in cirrhotic liver, which can contribute to the induction of enhancement of liver regeneration.…”

“…The resected liver specimens from DMN-treated rats were used for histological assessment of liver fibrosis and cirrhosis. Development of cirrhosis was confirmed by macroscopic inspection and histological examination, in which pseudonodules with various sizes and fibrous connective tissue bridges were seen as reported previously [18]. Twenty-four hours after hepatectomy, rats were anesthetized and rhHGF-activator (5 g protein/ml of saline with 0.1% bovine serum albumin and 0.1% 3-[(3-Cholamidopropyl) dimethylammonio]-1-propanesulfonic acid [CHAPS] per rat) or its vehicle (1 mL) was administered via the portal vein after a midline laparotomy according to our previous methods [17].…”

“…For the development of cirrhosis, rats were injected intraperitoneally with 1% DMN dissolved in saline at 1 mL/kg of body weight on 3 consecutive days a week for 3 weeks [19,20]. Five days after the last DMN injection, DMN-treated rats (50 rats per experiment) were anesthetized with ether and 45% partial hepatectomy was performed by excision of the left lateral lobe of the liver [18]. The resected liver specimens from DMN-treated rats were used for histological assessment of liver fibrosis and cirrhosis.…”

Excretion and Metabolism of DA-7867, a New Oxazolidinone, in Rats

“…Intravenous administration of DA-7867 to control rats and rats with liver cirrhosis induced by dimethylnitrosamine Rats (weight, 130-160 g) were induced for liver cirrhosis by dimethylnitrosamine [10]. Rats were repeatedly injected intraperitoneally with 1% dimethylnitrosamine (the dimethylnitrosamine powder was dissolved in 0.9% NaCl-injectable solution) at 1 ml/kg on three consecutive days a week for 4 weeks.…”