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

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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.

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About the authors

Pavel O. Inozemcev

Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences

Author for correspondence.
Email: p.inozemcev@rambler.ru
ORCID iD: 0000-0002-6623-0998
SPIN-code: 1026-2634

Cand. Sci. (Pharm.), Senior Researcher, Depart. of Biomedical Research and Technologies

Russian Federation, Irkutsk

Georgy E. Grigoriev

Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences

Email: grigorevgeorgij58@gmail.com
ORCID iD: 0009-0007-5183-7352
SPIN-code: 3522-5070

Cand. Sci. (Vet.), Junior Researcher, Depart. of Biomedical Research and Technologies

Russian Federation, Irkutsk

Ilya S. Kurgansky

Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences

Email: kurg.is@mail.ru
ORCID iD: 0000-0003-4386-5162
SPIN-code: 1768-5446

MD, Cand. Sci. (Med.), Senior Researcher, Depart. of Biomedical Research and Technologies

Russian Federation, Irkutsk

Svetlana A. Lepekhova

Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences

Email: lepekhova_sa@mail.ru
ORCID iD: 0000-0002-7961-4421
SPIN-code: 3019-8040

Dr. Sci. (Biol.), Head of Depart., Depart. of Biomedical Research and Technologies

Russian Federation, Irkutsk

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2. Fig. 1. Kaplan–Meier survival results in experimental groups with induced acute toxic liver injury compared to animals receiving placebo. Group 1 — subcutaneous administration of 0.5 ml of saline; Group 2 — subcutaneous administration of 0.5 ml of isolated HGF (Sigma-Aldrich — Hepatocyte Growth Factor) (n=30); Group 4 — subcutaneous administration of 0.5 ml of lyophilic composition 12 hours after CCl4 administration (n=30); Group 5 — subcutaneous administration of 0.5 ml of lyophilic composition immediately after CCl4 administration (n=15); Group 6 — subcutaneous administration of 0.5 ml of lyophilisate of isolated hepatocytes.

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