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

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.

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Journal
Kazan medical journal
Published
2024-12-12
DOI
https://doi.org/10.17816/kmj634419
Primary Topic
Liver Disease Diagnosis and Treatment
Type
article
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article

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

I. S. Kurganskiy, С. А. Лепехова, Pavel O. Inozemcev, G.E. Grigoriev
Kazan medical journal
Liver Disease Diagnosis and Treatment
article

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

I. S. Kurganskiy, С. А. Лепехова, Pavel O. Inozemcev, G.E. Grigoriev
article en

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.

Kazan medical journalVol. 106(1)
Siberian Branch of the Russian Academy of Sciences (RU)
Good health and well-being
Openalex Percentile: Top 64%
Liver Disease Diagnosis and Treatment
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