Yasushi Yamashita

Amelioration of Disordered Hepatic Protein Synthesis by the Deleted Form of Hepatocyte Growth Factor in Models of Liver Failure in Rats

Because the liver plays an important role in protein synthesis and cholesterol metabolism and reductions in these functions are observed in almost all hepatic disorders, the effects of the deleted form of hepatocyte growth factor (dHGF) on disordered hepatic protein synthesis were studied in various liver‐injured rat models using Wistar male rats.

Deleted form of hepatocyte growth factor ameliorates the mortality rate of severe thermal injury in rats

BACKGROUND The modulating effects of the deleted form of hepatocyte growth factor (dHGF) on burn-induced mortality rates and hepatic protein synthesis were studied in rats. METHODS Rats were anesthetized, subjected to a 40% full-thickness scald burn, and divided into 2 groups receiving dHGF and vehicle. RESULTS In normal rats, dHGF-treatment (1 mg/kg intravenously, twice daily) for 5 days increased the circulating plasma volume. In burned rats that were receiving vehicle, the survival rate on day 23 after the burn was 27%. The serum albumin levels were decreased and did not reverse to the normal levels until day 23 after the burn. Serum alpha 2-concentration in the injured rats was increased, whereas serum levels of transferrin, total protein, and high-density lipoprotein-cholesterol were decreased. The treatment of animals with dHGF (1 mg/kg intravenously, 3 times daily) for 3 days increased the survival rate on day 23 by 64%. In the animals treated with dHGF for 3 or 6 days, serum alpha 1-, alpha 2-, and beta-globulin concentrations were increased by the dHGF treatment. The serum levels of albumin, transferrin, total protein, and high-density lipoprotein-cholesterol reversed to normal levels or higher. CONCLUSIONS Our data show that dHGF treatment may attenuate the decrease of the circulating plasma volume after burn and reduce a high risk of burn shock. It is also indicated that dHGF accelerates synthesis of not only acute-phase reactants but also other hepatic proteins such as albumin and transferrin on severe burn injury. These findings suggest that the appropriate upregulation of hepatic protein synthesis induced by dHGF may accelerate the physiologic recovery process after thermal injury and contribute to ameliorating the burn-induced death.

Pretreatment with a deleted form of hepatocyte growth factor (DHGF) prevents the mortality of plasma-loss-induced hypovolemic shock in rats

Severe trauma, infection, burn, pancreatitis and major surgery often induce circulatory collapse leading to multiple organ failure and death. It is hypothesized that therapy for the attenuation of circulatory collapse may improve the prognosis in these diseases. Previous work has documented that pretreatment with a deleted form of hepatocyte growth factor (dHGF) in normal rats increases the circulating plasma volume that reflects its accelerating action of hepatic protein synthesis. Therefore, the effects of pretreatment with dHGF on hypovolemic shock models were studied in rats. Rats were intravenously administered dHGF (1 mg/kg, twice daily for 5-6 days) or vehicle, and subjected to a 25% total body surface area full-thickness burn or a trypsin-induced acute pancreatitis. In rats that were receiving vehicle, survival rates on day 7 after injury induction were 12% in the burn model and 5% in the pancreatitis model, respectively. In both models, hematocrit values were apparently increased and circulating plasma volumes were decreased compared to sham-operated rats at 6 h after injury induction. The pretreatment of animals with dHGF increased the survival rates on day 7 to 40% in the burn model and 29% in the pancreatitis model. dHGF-treatment in normal rats decreased the hematocrit values and increased the circulating plasma volumes, and these changes of hematocrit value and circulating plasma volume were also maintained after injury induction. These findings suggest that dHGF pretreatment prevents the mortality in the severe burn and acute pancreatitis, and that its effect may contribute to ameliorating the progressing of plasma-loss-induced hypovolemia.