Environmentally relevant concentrations of butyl benzyl phthalate triggered oxidative stress and apoptosis in adult zebrafish (Danio rerio) liver: Combined analysis at physiological and molecular levels

Butyl benzyl phthalate (BBP), a typical phthalate plasticizer, is frequently detected in aquatic environments, but its possible effects on fish liver are unknown. In this study, adult zebrafish were exposed to 5-500 μg/L BBP and cultured for 28 days. The toxicity mechanism of environmentally relevant concentrations of BBP in the liver was explored using integrated biomarker response (IBR), molecular docking, and histopathological analysis, based on the tests of oxidative stress, apoptosis, and tissue damage, respectively. The results revealed that exposure to 500 μg/L BBP caused lipid peroxidation and DNA damage and induced inflammatory responses in the liver and intestinal tissues. The accumulation of reactive oxygen species (ROS) is the primary manifestation of BBP toxicity and is accompanied by changes in the activities of antioxidant and detoxification enzymes. Notably, the pro-apoptotic genes (p53 and caspase-3) were still significantly upregulated in the 50 μg/L and 500 μg/L treatment groups on day 28. Moreover, BBP interfered with apoptosis by forming a stable complex with apoptosis proteins (P53 and Caspase-3). Our findings are helpful for understanding the toxicity mechanisms of BBP, which could further promote the assessment of the potential environmental risks of BBP.