A Critical Review of Polychlorinated Biphenyls Metabolism, Metabolites, and Their Correlation with Oxidative Stress

Abstract

Polychlorinated biphenyls (PCBs) are notorious persistent organic pollutants that were banned in the last century. However, PCBs still remain ubiquitous in the ecosystem due to their persistence and bioaccumulative potency against environmental and biological degradation. Albeit there is no longer the permission of commercial production of PCBs, they were continuously released into global biota via illegal disposal of e-waste or as byproducts of industrial supplies. The role of oxidative stress is often implicated in PCBs' toxicology. PCBs, especially coplanar ones, have a high affinity toward aryl hydrocarbon receptors and inducing CYP1A1, which is considered as a source of oxidative stress. Although commercial PCBs and coplanar individual PCBs, for example, PCB 77 and 126, induced oxidative stresses have been extensively investigated, PCB metabolite-induced oxidative stress has received less attention. PCBs can undergo phase I metabolism which metabolizes the parent PCBs into hydroquinone/semiquinone/quinone metabolites as a futile redox cycle, producing downstream reactive oxygen species (ROS) as byproducts. PCBs can also undergo phase II metabolism yielding methylsulfonyl metabolites that deplete glutathione and such. PCB metabolites induce oxidative stress generally via direct production of ROS or indirect scavenge antioxidant and inhibit antioxidant enzymes, disturbing cellular redox balance. This review aims to provide a critical summary of PCBs metabolism, PCBs parents, and daughter metabolite-induced oxidative stress. We especially focus on the connection between parent PCBs and downstream metabolites, to encourage research associated with PCB metabolite-induced oxidative stress.

Polychlorinated Biphenyls (PCBs): Risk Factors for Autism Spectrum Disorder?

“…Genes in this ontogeny included cytochrome P450 monooxygenases, which are involved in human metabolism of PCBs [183]. In light of experimental evidence demonstrating that hydroxylated PCB metabolites alter dendritic arborization in vitro [122,123,125] and increase reactive oxygen species and cell death in the rodent cerebellum [184,185], these data suggest the possibility that PCBs may interact with polymorphisms in cytochrome P450 to modulate individual risk for ASD. Other studies have similarly identified polymorphisms in genes related to toxicant metabolism enriched in individuals with ASD compared to neurotypical controls [165].…”

Review on Chitosan Intake and Enhancement in Fecal Excretion of Endocrine Disruptors

“…Poly-chlorinated biphenyls are chlorine containing compounds with 209 members [20]. Biotransformation occurs mainly in liver aided by cytochrome P450 enzyme system.…”

“…Biotransformation occurs mainly in liver aided by cytochrome P450 enzyme system. Biotransformation mainly depends on the chlorination of PCB; highly chlorinated PCB are resistant to metabolism and are found to deposit in adipose tissues whereas low chlorinated PCBs are prone to biotransformation into respective metabolites [20]. In phase I they undergo hydroxylation to form monohydroxylated PCB which further forms dihydroxylated PBC.…”

Oxidative Stress and Antioxidant Response in Populations of the Czech Republic Exposed to Various Levels of Environmental Pollutants

“…POPs represent a broad class of chemicals that have been used in industrial applications, pest and disease control, or to increase crop production. Similar to PAHs, they bind to the aryl hydrocarbon receptor, and their metabolism involves CYP1A1 activation subsequently leading to ROS production [ 13 ].…”