Experimental study of the effectiveness of ademethionine and inosine glycyl-cysteinyl-glutamate disodium in the treatment of dichloroethane-induced toxic hepatitis

Introduction. Currently, in the search for drugs for the toxic liver damage treatment, considerable attention is paid to glutathione preparations and its metabolic precursors. There are separate reports in the literature on the hepatoprotective and antifibrotic effects of glutathione disulfide in viral liver lesions, which gives grounds for their additional study when exposed to hepatotropic substances.

Material and methods. Performing a comparative assessment of the hepatoprotective effect of inosine glycyl-cysteinyl-glutamate disodium and ademetionine on the model of dichloroethane-induced toxic hepatitis in rats was carried out with the formation of the following experimental groups of animals: no treatment; with the introduction of physiological saline; with the introduction of inosine glycyl-cysteinyl-glutamate disodium; with the introduction of ademetionine, as well as a group of intact animals. The study drugs were administered intraperitoneally for 10 days. In the course of the study, biochemical indicators of cytolytic and cholestatic syndromes of liver damage were determined, the activity of its detoxification system and plastic function were assessed.

Results. In groups that did not receive treatment, but received physiological saline, the lethality of experimental animals by the 20th day of observation was 40%, in the group treated with ademetionine — 10%. In the group treated with inosine glycyl-cysteinyl-glutamate disodium, no death of animals was observed. The use of inosine glycyl-cysteinyl-glutamate disodium led to a more significant decrease in the indicators of cytolytic and cholestatic syndromes, as well as normalization of the functional activity of the liver (restoration of the content of glutathione in the liver tissue) and its plastic function (restoration of the level of total blood serum protein and glycogen content in the liver parenchyma) to a greater extent than with ademetionine.

limitation. The experimental study was carried out on outbred male rats weighing 180–220 g, kept under standard vivarium conditions in one cage, no more than 6 individuals, divided into groups by randomization with the exclusion of weakened and sick animals from the study.

Conclusion. The study provided an experimental justification for further study of the hepatoprotective effect of inosine glycylcysteinylglutamate disodium in toxic liver damage.

Compliance with ethical standards. This experimental study was approved by the decision of the ethical committee (extract from protocol No. 247 dated November 22, 2022) of the Military medical academy of S.M. Kirov, Ministry of Defense of the Russian Federation. Animal handling was organized in accordance with the rules of good laboratory practice (GOST 33044–2014).

Author contribution:
Orlov Yu.V. — design of the study, setting up the experiment, collecting and processing the material, statistical analysis, writing the text;
Gaiduk S.V., Kuzmich V.G. — concept, editing.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.

Conflict of interest. The authors declare that there is no conflict of interest.

Financing. The study had no sponsorship.

Received: May 10, 2023 / Accepted: May 26, 2023 / Published: June 30, 2023