Integrative assessment of potential effects of dioxins and related compounds in wild Baikal seals (Pusa sibirica): Application of microarray and biochemical analyses

Hirakawa, Shusaku; Imaeda, Daisuke; Nakayama, Kei; Udaka, Masayuki; Kim, Eun Young; Kunisue, Tatsuya; Ogawa, Masako; Matsuda, Tomonari; Matsui, Saburo; Петров, Е. А.; Batoev, Valeriy; Tanabe, Shinsuke; Iwata, Hisato

doi:10.1016/j.aquatox.2011.05.007

Cited by 13 publications

(30 citation statements)

References 40 publications

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“…35−37 In our previous study, levels of malondialdehyde, a lipid peroxide and biomarker of oxidative stress, displayed a significant positive correlation with CYP1A2 mRNA expression levels. 20 In addition, the levels of selenoprotein P were positively correlated with CYP1A2, CYP1A1, and CYP1B1 mRNA levels. 20 These results suggest that oxidative stress and the counteracting antioxidant responses are elicited by ROS produced through the metabolism of recalcitrant PCB congeners by CYP1 isozymes.…”

Section: ■ Results and Discussionmentioning

confidence: 97%

“…The reliability of the mRNA quantitative data obtained by our custom microarray has been confirmed by examining the correlations of the expression levels of CYP1 genes measured by both microarray and real-time RT-PCR. 20 The findings indicated that this microarray can provide data sets of the expression levels of certain genes with high accuracy. Thus, we attempted to assess the potential effects of OH-PCBs in the Baikal seal by the gene expression analysis using our microarray.…”

Section: ■ Results and Discussionmentioning

confidence: 98%

“…20 This microarray assessment indicated that chronic exposure to DRCs alters the hepatic transcription profile of genes related to oxidative stress, iron ion homeostasis, and inflammatory responses. These results suggested that our custom microarray can be a useful monitoring tool for screening alterations in the gene expression by other organohalogen contaminants including PCBs and their hydroxylated metabolites in the wild Baikal seals.…”

Section: ■ Introductionmentioning

confidence: 99%

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Toxicological Assessment of Polychlorinated Biphenyls and Their Metabolites in the Liver of Baikal Seal (Pusa sibirica)

Nomiyama

Hirakawa

Eguchi

et al. 2014

Environ. Sci. Technol.

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We have previously reported that high accumulation of dioxins and related compounds induced cytochrome P450 (CYP 1s) isozymes in the liver of wild Baikal seals, implying the enhanced hydroxylation of polychlorinated biphenyls (PCBs). The present study attempted to elucidate the residue concentrations and patterns of PCBs and hydroxylated PCBs (OH-PCBs) in the livers of Baikal seals. The hepatic residue concentrations were used to assess the potential effects of PCBs and OH-PCBs in combination with the analyses of serum thyroid hormones, hepatic mRNA levels, and biochemical markers. The hepatic expression levels of CYP1 genes were positively correlated with the concentration of each OH-PCB congener. This suggests chronic induction of these CYP1 isozymes by exposure to PCBs and hydroxylation of PCBs induced by CYP 1s. Hepatic mRNA expression monitoring using a custom microarray showed that chronic exposure to PCBs and their metabolites alters the gene expression levels related to oxidative stress, iron ion homeostasis, and inflammatory responses. In addition, the concentrations of OH-PCBs were negatively correlated with L-thyroxine (T4) levels and the ratios of 3,3',5-triiodo-L-thyronine (T3)/reverse 3,3',5'-triiodo-L-thyroninee (rT3). These observations imply that Baikal seals contaminated with high levels of OH-PCBs may undergo the disruption of mechanisms related to the formation (or metabolism) of T3 and T4 in the liver.

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Section: ■ Results and Discussionmentioning

confidence: 97%

Section: ■ Results and Discussionmentioning

confidence: 98%

Section: ■ Introductionmentioning

confidence: 99%

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Toxicological Assessment of Polychlorinated Biphenyls and Their Metabolites in the Liver of Baikal Seal (Pusa sibirica)

Nomiyama

Hirakawa

Eguchi

et al. 2014

Environ. Sci. Technol.

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“…Immunosuppression resulting from chronic exposure to environmental contaminants, including PCBs, has been considered a contributing factor to this outbreak. , In addition, we recently confirmed the accumulation of OH-PCBs in the livers of Baikal seals and suggested the impact OH-PCBs may have on thyroid function . It has also been suggested that the hydroxylation of coplanar (non- and mono- ortho chlorine substituted) and noncoplanar (di-, tri-, and tetra- ortho chlorine substituted) PCBs is enhanced by the induction of hepatic CYPs following exposure to dioxins and related compounds. , Moreover, we have sequenced the complementary DNAs (cDNAs) of Baikal seal CYP (bsCYP) 1A1, 1A2, and 1B1 open reading frames and built their homology models. , However, the contribution of these bsCYPs to the metabolism of PCBs has not yet been directly investigated. Thus, we investigated the enzymatic potencies of bsCYPs in PCB metabolism.…”

Section: Introductionmentioning

confidence: 51%

“…We have previously reported that this liver sample contained relatively high levels of total 2,3,7,8-tetrachlorodibenzo- p -dioxin toxic equivalents (TEQs; 85 pg/g wet wt.) and bsCYP1A1, 1A2, and 1B1 mRNAs …”

Section: Resultsmentioning

confidence: 99%

In Vitro and in Silico Analyses for Predicting Hepatic Cytochrome P450-Dependent Metabolic Potencies of Polychlorinated Biphenyls in the Baikal Seal

Yoo

Hirano

Mizukawa

et al. 2015

Environ. Sci. Technol.

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The aim of this study was to understand the cytochrome P450 (CYP)-dependent metabolic pathway and potency of polychlorinated biphenyls (PCBs) in the Baikal seal (Pusa sibirica). In vitro metabolism of 62 PCB congener mixtures was investigated by using liver microsomes of this species. A decreased ratio of over 20% was observed for CB3, CB4, CB8, CB15, CB19, CB22, CB37, CB54, CB77, and CB105, suggesting the preferential metabolism of low-chlorinated PCBs by CYPs. The highly activated metabolic pathways in Baikal seals that were predicted from the decreased PCBs and detected hydroxylated PCBs (OH-PCBs) were CB22 to 4'OH-CB20 and CB77 to 4'OH-CB79. The total amount of OH-PCBs detected as identified and unidentified congeners accounted for only a 3.8 ± 1.7 mol % of loaded PCBs, indicating many unknown PCB metabolic pathways. To explore factors involved in CYP-dependent PCB metabolism, we examined the relationships among the structural and physicochemical properties of PCBs, the in silico PCB-CYP docking parameters, and the in vitro PCB decreased ratios by principal component analysis. Statistical analysis showed that the decreased PCB ratio was at least partly accounted for by the substituted chlorine number of PCBs and the distance from the Cl-unsubstituted carbon of docked PCBs to the heme Fe in CYP2A and 2B.

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Antioxidative defense and oxidative stress in ringed seals (Pusa hispida) from differently polluted areas

Kanerva¹,

Routti²,

Tamuz³

et al. 2012

Aquatic Toxicology

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Integrative assessment of potential effects of dioxins and related compounds in wild Baikal seals (Pusa sibirica): Application of microarray and biochemical analyses

Cited by 13 publications

References 40 publications

Toxicological Assessment of Polychlorinated Biphenyls and Their Metabolites in the Liver of Baikal Seal (Pusa sibirica)

Toxicological Assessment of Polychlorinated Biphenyls and Their Metabolites in the Liver of Baikal Seal (Pusa sibirica)

In Vitro and in Silico Analyses for Predicting Hepatic Cytochrome P450-Dependent Metabolic Potencies of Polychlorinated Biphenyls in the Baikal Seal

Antioxidative defense and oxidative stress in ringed seals (Pusa hispida) from differently polluted areas

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