BIOCHEMICAL ASPECTS OF INTERPRETING OXIDATIVE PROCESS INTENSITY IN THE LIVER OF RATS WITH ACETAMINOPHEN-INDUCED INJURY AFTER PARTIAL HEPATECTOMY
DOI:
https://doi.org/10.31861/biosystems2025.03.333Keywords:
metallothioneins, protein SH-group, carbonyl derivatives, partial hepatectomy, acetaminophen, toxic injury, liver regeneration, liverAbstract
Impaired liver regeneration after partial hepatectomy under conditions of prior toxic injury is a relevant problem in experimental and clinical biochemistry. Previous acetaminophen-induced injury creates an unfavorable redox environment for hepatic parenchymal restoration. In this context, particular importance is attached to the study of metallothioneins as redox-active, thiol-containing proteins, as well as indicators of oxidative protein modification, which reflect the intensity and direction of oxidative processes within the cell. Our study is devoted to the assessment of the content of metallothioneins and the degree of oxidative protein modification in the mitochondrial and cytosolic fractions of rat liver subjected to partial hepatectomy after acetaminophen intoxication. The experiments were performed on white outbred rats divided into two groups: animals that underwent partial hepatectomy by the Mitchell and Willenbring method (C/PH) and animals that underwent two-thirds liver resection after acute paracetamol-induced injury, modeled by intragastric administration of the xenobiotic at a dose of 1250 mg/kg body weight once daily for two days in the form of a 2% starch gel suspension (TI/PH). Tissue sampling was performed at 24, 48, 72, and 168 h after surgical intervention. The content of metallothioneins and the levels of protein carbonylation and free SH groups were assessed using spectrophotometric biochemical methods. The results of the study showed that in animals with partial hepatectomy after toxic injury caused by acetaminophen, the level of metallothioneins in the liver's cytosolic fraction increases throughout the entire regeneration period. At the same time, progressive depletion of the thiol pool and an increase in protein carbonylation levels were recorded in the mitochondrial fraction, indicating the predominance of pro-oxidant processes. The enhancement of oxidative protein modification was accompanied by a decrease in the content of free SH groups, which is consistent with a disturbance of redox balance and depletion of the thiol-disulfide system. Interpretation of the obtained results indicates that the intensity of oxidative processes in the regenerating liver after acetaminophen-induced injury is determined by the compartment-specific interaction between the metallothionein system and the thiol status of proteins. The identified changes have important theoretical significance for understanding the molecular mechanisms of liver regeneration and may be used for the biochemical interpretation of the state of regenerating parenchyma under toxic injury.
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