Effect of a lyophilic composition containing hepatocyte growth factor on the survival of rats under conditions of toxic liver injury

Abstract

BACKGROUND: The apparent tendency towards an increase in the number of patients with liver failure serves as a basis for searching for new substances that meet modern requirements for efficiency in the treatment of this pathology. AIM: To evaluate the survival rate of animals under the influence of a lyophilic composition in modeling acute toxic liver damage. MATERIAL AND METHODS: The studies were performed in vivo using Wistar rats (n=135). Acute toxic liver injury was modeled in male rats weighing 200–250 g using subcutaneous administration of CCl4 at a dosage of 0.5 mg per 100 g of animal weight. Animals were divided into groups depending on the administered drug: group 1 — subcutaneous injection of saline at a dosage of 0.5 ml (n=30); group 2 — subcutaneous injection of isolated hepatocyte growth factor (HGF) 0.5 ml (n=30); group 3 — administration of 0.5 ml of antibodies to HGF into the tail vein (n=15); group 4 — subcutaneous injection of 0.5 ml of lyophilic composition 12 h after CCl4 administration (n=30); group 5 — subcutaneous injection of 0.5 ml of lyophilic composition immediately after CCl4 administration (n=15). Group 6 — subcutaneous injection of 0.5 ml of lyophilisate of isolated hepatocytes (n=15). The duration of the study was 6 days. Survival in the groups was estimated using the Kaplan–Meier curves. The stratified log-rank test was used to assess the significance of differences in survival. The study data were statistically processed using the Statistica 10.0 program; differences were considered statistically significant at p 0.05. RESULTS: Administration of the lyophilic composition enriched with hepatocyte growth factor significantly increased the lifespan of animals compared to the control group. Analysis of outcomes between the experimental and control groups revealed that the significance level of differences in the mortality rate between the group receiving exogenous HGF as a treatment (group 2) and the control group was p 0.0001; between the experimental group receiving a subcutaneous injection of 0.5 ml of the lyophilic composition 12 hours after CCl4 administration (group 4) and the control group — p 0.0001. Less significant differences were observed in the experimental group that received the lyophilic composition immediately after CCl4 injection (group 5) — p=0.4103. In addition, low survival was noted in the group of animals that received isolated hepatocytes (group 6) — p=0.3263. Low survival was explained by the small amount of HGF in the isolated hepatocytes medium. CONCLUSION: A lyophilic composition containing HGF as an active substance improves the survival of rats in a model of acute toxic liver injury.