Peptide drugs in hydrazine-induced liver injury: experimental evaluation

Abstract

Toxic liver disease is a group of diseases associated with the hepatotoxic effects of various chemicals, causing morphological changes in organ tissue and associated functional impairment. The liver's high sensitivity to chemicals is due to its leading role in their metabolism. The biotransformation of toxicants can lead to the formation of highly reactive intermediates and the initiation of free radical oxidation, which can lead to liver damage. More than 40 groups of chemicals are capable of causing liver damage when ingested by humans and animals. Hydrazine derivatives, which are used in the chemical industry as components of rocket fuels and pharmaceuticals, occupy a significant place among them. Due to intensive rocket and space activities, poisoning by components of liquid rocket fuels, particularly unsymmetrical dimethylhydrazine, remains a common problem. Liver damage due to medication use also remains a common problem. Hydrazine derivatives have also found application as medicinal agents, with the anti-tuberculosis drug isoniazid being the most interesting. The objective of this study was to investigate the efficacy of peptide preparations based on the oxidized form of glutathione in toxic liver damage caused by hydrazine derivatives. The efficacy of disodium inosine glycylcysteinyl glutamate in acute UDMH poisoning was demonstrated for the first time. Disodium glutamylcysteinylglycine and disodium inosine glycylcysteinyl glutamate were shown to reduce the severity of developing toxic morphofunctional changes in the liver caused by anti-tuberculosis drugs, with the effect of IGCGN being more pronounced.