Dose-Dependent Hepatotoxicity of Diethyl Phthalate in Female Wistar Rats

Phthalates are a class of compounds commonly used as plasticizers in various industrial and consumer products. In line with the increasing environmental and biological exposure concerns regarding these compounds, this study investigated the dose-dependent effects of diethyl phthalate (DEP) on the liver in a subacute rat model. Diethyl phthalate (DEP) was given orally by gavage to female Wistar albino rats at doses of 100, 300, and 600 mg/kg body weight per day for 21 days in order to assess liver tissue and associated function test levels. Liver function was evaluated by analyzing serum biochemical data. Liver tissues were evaluated using histopathological staining (H&E and Masson's trichrome staining), immunohistochemical analysis of IL-1β and TGF-β, tissue ELISA for IL-6 and TNF-α, and comet assay to determine DNA damage. DEP exposure was found to cause significant, dose-dependent histopathological changes in liver tissue, including hepatocyte necrosis, cytoplasmic vacuolization, sinusoidal dilation, and vascular congestion. AST levels were significantly increased compared to the control group, while no significant changes were observed in other serum biochemical parameters. Compared to the control group, the expression of pro-inflammatory cytokines (IL-6 and TNF-α), IL-1β, and TGF-β was found to be elevated in the DEP-treated groups, and their levels increased with increasing exposure dose. DEP exposure also caused significant DNA damage in liver tissue. These findings indicate that despite an increase in AST levels observed in subacute DEP exposure, there were limited changes in serum biochemical parameters; serum liver enzymes alone may not fully reflect the extent of hepatic damage, and DEP can cause significant inflammatory, histopathological, and genotoxic effects in liver tissue.