Liver fibrosis model: Investigation of the hepatotoxic effects of different doses of nonylphenol exposure

Nonylphenol (NP) is a widely used chemical in industrial and household products, known for its ability to easily leach into the environment and its endocrine-disrupting effects. The liver, being the central organ in the metabolism of toxic substances, is one of the primary targets in NP exposure. NP exposure can lead to severe structural and functional impairments, including the development of fibrosis. This study was conducted to evaluate the toxic effects of different doses of NP exposure on rat liver tissue and examine possible dose-dependent changes. Five groups were formed: control, sham, low dose (NP1), medium dose (NP2), and high dose (NP3). Body weights were measured on days 1 and 16 of the experiment; significant weight gain was observed in the control group (p<0.05), whereas significant weight loss was detected in the high dose NP3 group (p<0.01). At the end of the experiment, organ weights were recorded, with liver weights showing significant increases in the NP3 group (p<0.01) and NP2 group (p<0.05) compared to controls. Histopathological examination revealed that NP exposure caused hepatocyte degeneration, sinusoidal dilation, inflammatory cell infiltration in the portal area, and fibrotic changes. Immunohistochemical analyses demonstrated a significant increase in the expression of TGF-β1, TLR-4, and α-SMA in liver tissue following NP administration. Notably, TGF-β1 expression was significantly higher in all NP groups compared to control and sham groups (p<0.001), TLR-4 expression showed significant differences paralleling increasing NP doses (p<0.001), and α-SMA expression was significantly elevated only in NP2 and NP3 groups (p<0.001). Dose-dependent increases in α-SMA expression were statistically supported in NP1–NP3 and NP2–NP3 comparisons (p<0.001). Biochemical evaluations indicated a significant increase in malondialdehyde (MDA) levels (p<0.001) and a marked decrease in superoxide dismutase (SOD) activities (p<0.001). The findings reveal that nonylphenol activates oxidative stress, inflammation, and fibrosis pathways at high doses, resulting in histopathological damage in the liver. In conclusion, NP exposure is an important risk factor in oxidative stress-related organ toxicity, with effects that increase in a dose-dependent manner.