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Effects of plastic additives on precision cut liver slices (PCLS) from Atlantic cod (Gadus morhua)
Summary
Researchers exposed Atlantic cod liver slices to plastic additives—MEHP, BPA, and benzotriazoles—and found that BPA triggered estrogenic effects, significantly increasing vitellogenin protein synthesis and upregulating estrogen-related genes, while mixture exposures suggested possible antagonistic and synergistic interactions that warrant further investigation.
A vast amount of the plastic we use end up in the ocean and estimates suggest a doubling of plastic in the ocean, to 250 million tonnes by 2025. Plastic contain additives such as phthalates, and these are known to have adverse health effects on living organisms. The additives may leach from products into the environment. Fish liver is a target organ for contaminants, due to its crucial role in biological functions such as metabolic homeostasis and detoxification processes, and precision-cut liver slices (PCLS) is a promising ex vivo system that is utilized within toxicology, using slices of complete liver tissue (Eide et al. 2014). The overall aim of the present study was to determine if exposure to plastic additives, such as phthalates, bisphenol A (BPA) and benzotriazoles (BT), have the potential to promote adverse effects in Atlantic cod (G. morhua). PCLS from six male juvenile Atlantic cod were exposed to 4 concentrations of mono-(2-ethylhexyl)-phthalate (MEHP), BPA and BT both singly and in mixtures ranging from 0.1-100 µM (MEHP), 0.022-22 µM (BPA) and 0.042-42 µM (BT). Histology and transmission electron microscopy (TEM) were used to assess pathological changes and ultrastructure of the exposed liver tissue. Vitellogenin produced by the hepatic tissue were analysed using ELISA, and the transcription levels of selected biomarker genes (vtg1, esr1, cyp1a, scdb, aclya, fabp1a, acox1, hnf4a and cebp) were measured using Q-PCR. A satisfactory assessment of the ultrastructure was not possible due to incomplete fixation of the PCLS with resulting lack of membranes and organelle structure. Histological evaluation did not show any pathological changes. An estrogenic effect was observed with a significant increase in vtg protein synthesis and upregulation of the vtg1 and esr1 genes following exposure to BPA and a mixture of the selected compounds. Hnf4a showed a significant downregulation following mixture exposure, where the BPA were suspected to be the main driver for this response however not inducing a significant downregulation in the single component exposure. A possible antagonistic mixture effect of the selected compounds might be questioned regarding the vtg protein, vtg1 and esr1 as well as a possible additive or synergistic effect regarding the hnf4a, and further investigation is warranted.