Effect of 4-n-nonylphenol and cadmium co-exposure on liver apoptosis and lipid metabolism in zebrafish (Danio rerio)

Nonylphenol (NP), a typical nonionic surfactant intermediate, is widely found in aquatic environments and exhibits biological toxicity. In aquatic environments, organisms face risks from co-exposure to NPs and the heavy metal cadmium (Cd); however, the combined toxicity of both has not been well studied. Therefore, this study aimed to evaluate the histological changes, antioxidant capacity, inflammation, and transcriptional responses in the zebrafish liver following exposure to environmental concentrations of 4-n-NP (45.38 and 453.8 nM) and Cd (54.55 nM), both individually and in combination experiments, over 28 days. Our results indicated that the 453.8 nM 4-n-NP-treated group generated significant oxidative stress during the initial 12 days, while on day 28, the combination of high concentrations of 4-n-NP and Cd also produced significant oxidative stress. Additionally, we observed mitochondrial swelling and endoplasmic reticulum expansion in liver cells across the various treatment groups. Significant dehydration of hepatocyte nuclei was observed in the combined exposure group, along with the deformation of nucleoli and solidification of margins. Combined exposure had a synergistic effect and triggered liver injury in zebrafish. The LPS concentration significantly increased in the NlCl group but decreased in the NhCl group, while the total bile acids exhibited 2.14-fold and 1.24-fold increases, respectively. Combined exposure disrupted liver lipopolysaccharide and bile acids in zebrafish. Meanwhile, combined exposure to 453.8 nM 4-n-NP and Cd caused apoptosis and induced DNA damage repair mechanisms, amplifying the toxic effects of each pollutant. Thus, this study contributes to our understanding of the health risks to aquatic organisms from the co-existence of nonionic surfactants and heavy metals. CAPSULE ABSTRACT: We revealed the effects of single and combined exposure to nonylphenols and heavy metals on the zebrafish liver in terms of enzyme activity, inflammation, degree of cellular damage, and gene expression. The accumulation of cellular reactive oxygen species and the occurrence of lipid peroxidation induced more severe cellular structural and functional damage, amplifying the singular toxic effect of the pollutants. Combined exposure showed synergistic effects, inhibiting cell growth and inducing DNA damage repair.