Dose–response relationship in the modeling acute toxic hepatitis in vivo as a basis for identifying new correction strategies

The exposure to chemical substances remains a priority risk factor for the health of the working population in the chemical, petrochemical, and pharmaceutical industries. The liver, as the primary organ of detoxification, is a primary target for many chemical agents, highlighting the necessity for in-depth studies of the pathogenetic mechanisms underlying its toxic damage. Understanding the temporal dynamics of changes in molecular-genetic and biochemical markers will enable more accurate determination of disease stages, prediction of disease progression, and formulation of pharmacological correction strategies. The aim of this study is to investigate the dynamics of changes in biochemical and molecular-genetic markers of damage when modeling acute toxic hepatitis at varying levels of toxic exposure. Material and methods. This work is based on data obtained from an experimental in vivo study, during which acute toxic hepatitis was modeled in outbred male rats aged 12–14 weeks and weighing 200–220 g using carbon tetrachloride, a widely used hepatotoxic agent in research settings. After 24 and 72 h of exposure, we assessed changes in the activity of key “liver” enzymes and in the expression of genes associated with antioxidant defense, the glutathione system, apoptosis regulation, and cell death. Results and discussion. In the first 24 h of carbon tetrachloride exposure, there was a statistically significant increase in alanine aminotransferase and aspartate aminotransferase activity, as well as a lesser extent increase in lactate dehydrogenase and alkaline phosphatase activity. After 72 h, changes in biochemical markers became more pronounced. The expression of studied genes changed ambiguously. In the dose-response relationship, differences were observed between the 24- and 72-hour periods, with steeper slopes for several biomarkers during the first 24 h. Conclusions . The data obtained in this study may contribute to and serve as a potential basis for developing strategies for pharmacological correction of toxic liver damage.