Targeted metabolome analysis of the dog brain exposed to PCBs suggests inhibition of oxidative phosphorylation by hydroxylated PCBs.

Canis lupus familiaris (domestic dog) possess a high capacity to metabolize higher-chlorinated polychlorinated biphenyls (PCBs) to thyroid hormone (TH)-like hydroxylated PCB metabolites (OH-PCBs). As a result, the brain could be at high risk of toxicity caused by OH-PCBs. To evaluate the effect of OH-PCBs on dog brain, we analyzed OH-PCB levels in the brain and the metabolome of the frontal cortex following exposure to a mixture of PCBs (CB18, 28, 70, 77, 99, 101, 118, 138, 153, 180, 187, and 202). 4-OH-CB202 and 4-OH-CB107 were major OH-PCBs in the brain of PCB-exposed dogs. These OH-PCBs were associated with metabolites involved in urea cycle, proline-related compounds, and purine, pyrimidine, glutathione, and amino-acid metabolism in dog brain. Moreover, adenosine triphosphate levels in the PCBs exposure group were significantly lower than in the control group. These results suggest that OH-PCB exposure is associated with a disruption in TH homeostasis, generation of reactive oxygen species, and/or disruption of oxidative phosphorylation (OXPHOS) in brain cells. Among them, OXPHOS disturbance could be associated with both disruptions in cellular amino-acid metabolism and urea cycle. Therefore, an OXPHOS activity assay was performed to evaluate the disruption of OXPHOS by OH-PCBs. The results indicated that 4-OH-CB107 inhibits the function of Complexes III, IV, and V of the electron transport chain, suggesting that 4-OH-CB107 inhibit these complexes in OXPHOS. The neurotoxic effects of PCB exposure may be mediated through mitochondrial toxicity of OH-PCBs in the brain.

Species- and Tissue-Specific Profiles of Polybrominated Diphenyl Ethers and Their Hydroxylated and Methoxylated Derivatives in Cats and Dogs.

The adverse effects of elevated polybrominated diphenyl ether (PBDE) levels, reported in the blood of domestic dogs and cats, are considered to be of great concern. However, the tissue distribution of PBDEs and their derivatives in these animals is poorly understood. This study determined the concentrations and profiles of PBDEs, hydroxylated PBDEs (OH-PBDEs), methoxylated PBDEs (MeO-PBDEs), and 2,4,6-tribromophenol (2,4,6-tri-BPh) in the blood, livers, bile, and brains of dogs and cats in Japan. Higher tissue concentrations of PBDEs were found in cats, with the dominant congener being BDE209. BDE207 was also predominant in cat tissues, indicating that BDE207 was formed via BDE209 debromination. BDE47 was the dominant congener in dog bile, implying a species-specific excretory capacity of the liver. OH-PBDE and MeO-PBDE concentrations were several orders of magnitude higher in cat tissues, with the dominant congener being 6OH-BDE47, possibly owing to their intake of naturally occurring MeO-PBDEs in food, MeO-PBDE demethylation in the liver, and lack of UDP-glucuronosyltransferase, UGT1A6. Relatively high concentrations of BDE209, BDE207, 6OH-BDE47, 2'MeO-BDE68, and 2,4,6-tri-BPh were found in cat brains, suggesting a passage through the blood-brain barrier. Thus, cats in Japan might be at a high risk from PBDEs and their derivatives, particularly BDE209 and 6OH-BDE47.

Contamination status of POPs and BFRs and relationship with parasitic infection in finless porpoises (Neophocaena phocaenoides) from Seto Inland Sea and Omura Bay, Japan.

Contamination status of brominated flame retardants (BFRs) and persistent organic pollutants (POPs) in blubber of finless porpoises (Neophocaena phocaenoides) stranded along the coasts of Seto Inland Sea and Omura Bay in Japan were investigated. Levels of PCBs, DDTs and CHLs were significantly higher than those of HCHs, HCB, PBDEs and HBCDs. Concentrations of PBDEs and HBCDs, as well as organochlorine compounds in males increased with body length (p<0.05). Among 14 PBDE congeners analyzed, BDE-47 was the predominant, which is similar to those generally reported in biota. PBDEs, HBCDs and PCBs showed no obvious temporal trend in concentrations during the study period, suggesting continuous environmental release of these chemicals. On the other hand, levels of DDT, CHLs and HCHs have decreased. Concentrations of PCBs in liver trematode infected individuals were significantly higher than those in not infected individuals, implying there could be a relationship between contaminant levels and parasitic infection.

Organohalogen compounds in deep-sea fishes from the western North Pacific, off-Tohoku, Japan: Contamination status and bioaccumulation profiles.

Twelve species of deep-sea fishes collected in 2005 from the western North Pacific, off-Tohoku, Japan were analyzed for organohalogen compounds. Among the compounds analyzed, concentrations of DDTs and PCBs (up to 23,000 and 12,400 ng/g lipid wt, respectively) were the highest. The present study is the foremost to report the occurrence of brominated flame retardants such as PBDEs and HBCDs in deep-sea organisms from the North Pacific region. Significant positive correlations found between delta(15)N ( per thousand) and PCBs, DDTs and PBDEs suggest the high biomagnification potential of these contaminants in food web. The large variation in delta(13)C (per thousand) values observed between the species indicate multiple sources of carbon in the food web and specific accumulation of hydrophobic organohalogen compounds in benthic dwelling carnivore species like snubnosed eel. The results obtained in this study highlight the usefulness of deep-sea fishes as sentinel species to monitor the deep-sea environment.