Paracetamol hepatotoxicity against the background of chronic stress: morphology and antioxidant gene activity in rats

Introduction. The study is devoted to the investigation of the effect of chronic stress on the toxic effect of paracetamol on the liver in rats. Paracetamol, widely used as an analgesic and antipyretic, can cause hepatotoxicity associated with the formation of reactive oxygen species and the development of oxidative stress when overdosed. Antioxidant mechanisms of the body’s defense include key genes such as Hmox1, Sod1, and Nqo1, which regulate the redox balance. Chronic stress reduces glutathione levels, which increases the vulnerability of the liver to toxic effects. The purpose of the work is to assess the toxicity of paracetamol in rats under the influence of chronic stress to develop new preventive approaches. Materials and methods. The experiment involved four groups of white outbred rats (6 males and 6 females), which were administered paracetamol (1000 mg/kg) and modelled chronic stress. Results. Morphological, biochemical, and genetic analyses were performed, and the liver weight coefficient was detected. In males, the liver weight coefficient varied: the minimum value (25.02) was recorded in the Stress group, the maximum (32.27) in the control group (p=0.001). In females in the «Stress» group, it was 34.77, which is lower compared to the «Paracetamol» (39.21; p=0.017) and «Paracetamol+Stress» (39.24; p=0.026) groups. Histomorphological analysis revealed signs of necrosis and inflammation with combined exposure. Genetic analysis showed an increase in Sod1 gene expression in males in the «Stress» group (p=0.001) and the highest Nqo1 level in the group with combined exposure to factors. Biochemical changes included decreased AST and ALT levels under stress and paracetamol. Limitations. For the experiment, laboratory animals of one biological species were used, and the toxicant was used in the only one concentration. Conclusion. The obtained results highlight the need for further study of the interaction of chronic stress and toxic factors for the development of preventive measures.