Hexachloronaphthalene (HxCN) impairs the dopamine pathway in an in vitro model of PC12 cells

Abstract

Among polychlorinated naphthalenes (PCNs), listed by the Stockholm convention as Persistent Organic Pollutants (POPs), hexachloronaphthalenes are considered the most toxic and raise the highest concern. Of these, 1,2,3,5,6,7-hexachloronaphthalanene (PCN67) is considered the main congener affecting human health due to its hepatotoxicity and its ability to disturb the reproductive, endocrine, and hematological systems. It is also prevalent in human serum/plasma, milk, and adipose tissue. However, little is known about its neurotoxicity, despite the fact that anorectic effects have been observed in workers occupationally exposed to PCNs and in animal research on PCN67. Since dopamine is involved in many aspects of food intake, the aim of this study was to confirm whether PCN67 affects dopamine synthesis in differentiated PC12 cells, a widely used model of neurosecretion. Our results show that exposure to PCN67 resulted in diminished dopamine content and release. Moreover, PCN67 also affected the expression of tyrosine hydroxylase and lowered the expression of vesicular monoamine transporter 1 (VMAT1). In addition, significantly lower expression of antioxidant enzymes, including catalase, glutathione peroxidase and copper/zinc superoxide dismutase, was observed in comparison to the vehicle. In conclusion, PCN67 appears to disturb dopaminergic transmission by altering tyrosine hydroxylation, reducing VMAT1 expression and impairing antioxidant protection. Our study provides a potential mechanism for how PCN67 may cause dopamine deficiency and contribute to neuronal death by affecting cellular antioxidant potency; however, this conclusion requires further research.