Effect of a lyophilic composition containing hepatocyte growth factor on rat survival in toxic liver injury

Abstract

BACKGROUND: The evident rise in the number of patients with liver failure underscores the need for new therapeutic agents that meet modern efficacy standards for treating this condition.

AIM: The study aimed to evaluate the survival rate of animals treated with a lyophilic composition in an experimental model of acute toxic liver injury.

METHODS: The study was conducted in vivo using Wistar rats (n = 135). Acute toxic liver injury was modeled in male rats weighing 200–250 g via subcutaneous administration of carbon tetrachloride (CCl₄) at a dose of 0.5 mg per 100 g of animal weight. The animals were divided into groups according to the administered substance. Group 1 was injected subcutaneously with 0.5 mL of physiological saline (n = 30). Group 2 was injected subcutaneously with 0.5 mL of isolated hepatocyte growth factor (HGF; n = 30). Group 3 was administered with 0.5 mL of HGF antibodies into the tail vein (n = 15). Group 4 was injected subcutaneously with 0.5 mL of lyophilic composition 12 hours after CCl₄ administration (n = 30). Group 5 was injected subcutaneously with 0.5 mL of lyophilic composition immediately after CCl₄ administration (n = 15). Group 6 was injected subcutaneously with 0.5 mL of a lyophilizate of isolated hepatocytes (n = 15). The study lasted six days. Kaplan–Meier survival curves were used to evaluate survival rates, and statistical significance of intergroup differences was evaluated using the stratified log-rank test. Statistical analysis was performed using Statistica 10.0 software. Differences were considered significant at p < 0.05.

RESULTS: The administration of the lyophilic composition enriched with HGF significantly increased animal survival compared with the control group. A comparison of mortality rates between the experimental and control groups revealed the following levels of significance: group 2 vs. control, p < 0.0001 (exogenous HGF administration); group 4 vs. control, p < 0.0001 (lyophilic composition administered 12 hours after CCl₄); group 5 vs. control, p = 0.4103 (lyophilic composition administered immediately after CCl₄); group 6 vs. control, p = 0.3263 (injection of isolated hepatocytes). The lower survival rate in group 6 was attributed to the insufficient HGF content in the isolated hepatocyte environment.

CONCLUSION: The lyophilic composition containing HGF as an active ingredient improves survival in rats with experimentally induced acute toxic liver injury.

Keywords

lyophilisate / hepatocyte growth factor / HGF / rats / survival rate

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Funding

Ministry of Science and Higher Education of the Russian FederationМинистерство науки и высшего образования Российской Федерации(075-00507-21-00)

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