Modulation of Neuro-Dopamine Homeostasis in Juvenile Female Atlantic Cod (Gadus morhua) Exposed to Polycyclic Aromatic Hydrocarbons and Perfluoroalkyl Substances

Abstract

The dopaminergic effect of PAH and PFAS mixtures, prepared based on environmental levels has been studied in juvenile female Atlantic cod (Gadus morhua). Benzo[a]pyrene, dibenzothiophene, fluorene, naphthalene, phenanthrene and pyrene were used to prepare a PAH mixture, while PFNA, PFOA, PFOS and PFTrA were used to prepare PFAS mixture. Cod were injected intraperitoneally twice, with either a low (1x) or high dose (20x) of each compound mixture or various combinations. After two week of exposure, levels of plasma 17β-estradiol (E2) were significantly high in high PAH/high PFAS treated groups. Dopamine: metabolite ratios (DOPAC/dopamine and HVA+DOPAC/dopamine) in brain homogenate changes with the levels of E2 in plasma except for high PAH/low PFAS and low PAH/high PFAS treated groups. In general, th mRNA levels inversely correlated with dopamine: metabolite ratios and gnrh2 mRNA levels. Respective decreases and increases of dr1 and dr2a after exposure to the high PAH dose were observed. Whereas, high PFAS exposure decreased both drs, leading to high plasma E2 concentrations. Other investigated endpoints suggest that these compounds at different doses and combinations have different toxicity threshold and mode of actions. These effects indicate potential alternations in feedback signalling processes within dopaminergic pathway by these contaminants.

Development of a PFAS reaction library: identifying plausible transformation pathways in environmental and biological systems

“…PFAS have been detected in soils, 1,2 sediments, 3 groundwaters, 4 rivers, 5 drinking water, 6 and waste water treatment plants. 7 The list of biological systems in which PFAS have been detected include humans, 8-10 sh, 11,12 birds, [13][14][15] frogs, 16 polar bears 17 and marine organisms. 18,19 The data in the peer-reviewed literature documenting the transformation and metabolic pathways of PFAS have not been captured in a systematic manner that readily supports prediction of the transformation products and metabolites of PFAS.…”

Effects of perfluoroalkyl substances (PFAS) and benzo[a]pyrene (BaP) co-exposure on phase I biotransformation in rainbow trout (Oncorhynchus mykiss)

“…Recently, Khan et al (2019) showed that exposure to environmentally relevant mixtures of PAHs and PFAS could modulate the neuro-dopamine homeostasis in female Atlantic cod. In addition, Dale et al…”

“…Our results indicate that exposure to PFAS/BaP binary mixtures altered CYP-like activity in vivo; however, those alterations were not observed in vitro. Previous studies have indicated that mixtures of PFAS and PAHs have the potential to alter biological processes in sh(Dale et al, 2020;Horvli, 2020;Khan et al, 2019). For instance,Khan et al (2019) demonstrated female Atlantic cod (Gadus morhua) exposed to mixtures of PFAS and PAHs in vivo had altered dopaminergic signaling, including the modulation of dopamine biosynthesis, catabolism, and its receptor expression.…”

“…Previous studies have indicated that mixtures of PFAS and PAHs have the potential to alter biological processes in sh(Dale et al, 2020;Horvli, 2020;Khan et al, 2019). For instance,Khan et al (2019) demonstrated female Atlantic cod (Gadus morhua) exposed to mixtures of PFAS and PAHs in vivo had altered dopaminergic signaling, including the modulation of dopamine biosynthesis, catabolism, and its receptor expression. Notably, the CYP19A1B gene expression was signi cantly decreased in the sh exposed to both low and high PAH doses and combined exposure to low PAH/high PFAS.…”

Revisiting the cellular toxicity of benzo[a]pyrene from the view of nanoclusters: size- and nanoplastic adsorption-dependent bioavailability

“…Bap has been proved to rapidly distribute in the organism after being inhaled 1 and induces oxidative stress and inflammation in pulmonary, 2 liver, 3 and neuronal systems. 4 However, the form in which it interacts with the biological system has seldom been seriously interpreted. In previous laboratory-based toxicity studies, Bap was usually treated as welldispersed, single molecules in aqueous solutions as normal soluble molecules or ions.…”