Mechanism of Biosynthesis of Methylsulfones from PCBs and Related Compounds

Mio, Takaya; Sumino, Kimiaki

doi:10.2307/3429885

Cited by 21 publications

(9 citation statements)

References 28 publications

(33 reference statements)

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“…POPs are detectable in virtually everyone, with exposure occurring through fatty animal food in particular [21]. Some POPs are conjugated to GSH for their metabolism [22][23][24], and exposure to high amounts of certain POPs in occupational or accidental settings increase serum GGT activity [25,26].…”

Section: Serum Ggt Activity As a Marker Of Exposure To Popsmentioning

confidence: 99%

Can persistent organic pollutants explain the association between serum γ-glutamyltransferase and type 2 diabetes?

2007

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The results of several epidemiological studies of serum γ-glutamyltransferase (GGT) led us to hypothesise that associations of GGT within its normal range with type 2 diabetes may reflect detrimental effects of xenobiotics found in the environment, such as persistent organic pollutants (POPs). Epidemiological observations showed that serum GGT activity within its normal range strongly predicted future type 2 diabetes; the predictability of diabetes from obesity was low with GGT at the low end of the normal range; and GGT showed a positive association with known markers of oxidative stress or inflammation. Experimental findings on cellular GGT suggest that serum GGT levels within the normal range may reflect oxidative stress related to the re-synthesis of intracellular glutathione; however, this interpretation is not completely satisfying because, in its role of regenerating intracellular glutathione, GGT activity should be antioxidative.

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Section: Serum Ggt Activity As a Marker Of Exposure To Popsmentioning

confidence: 99%

Can persistent organic pollutants explain the association between serum γ-glutamyltransferase and type 2 diabetes?

2007

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“…The structure-tissue affinity relationship study demonstrated that retention potential of live metabolites largely depends on the ortho -chlorine substitution and not the degree of chlorination. Interestingly, hydroxylated methylsulfonyl metabolites were discovered in the urine of mice that were treated with PCBs …”

Section: Metabolic Pathway Yielding Sulfur-containing Metabolitesmentioning

confidence: 99%

“…Interestingly, hydroxylated methylsulfonyl metabolites were discovered in the urine of mice that were treated with PCBs. 102 The rate of formation of MeSO 2 -metabolites is largely dependent on the degree of chlorination, that is, the less chlorinated congeners (tri-or tetra-) metabolize more rapidly than higher chlorinated ones (penta-or hexa-). 103 It is interesting to notice that 3-methylsulfonyl derivatives from a higher degree PCB have a relatively high affinity in liver and adipose tissues, whereas 4-methylsulfonyl derivatives have a relatively high affinity in lungs.…”

Section: Metabolic Pathway Yielding Sulfur-containing Metabolitesmentioning

confidence: 99%

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

Liu

Song

et al. 2020

Chem. Res. Toxicol.

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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.

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“…The other two, M b and M c , were presumably the precursors of M d because when the fraction was oxidized chemically, the two peaks were converted to the corresponding methylsulfones (M d ). Mio and Sumino (1985) identified 3-hydroxy-4-methylthio-2,5,2Ј,5Ј-tetraCB in the feces from rats, mice, and guinea pigs dosed with 2,5,2Ј,5Ј-tetraCB, suggesting that the precursor of the metabolite was 3,4-epoxide. The epoxide may have been opened by nucleophile attack of the sulfhydryl group and subsequently converted to the hydroxylated metabolite by dehydrogenation (Bakke et al, 1982).…”

Section: Haraguchi Et Almentioning

confidence: 99%

Comparative Metabolism of Polychlorinated Biphenyls and Tissue Distribution of Persistent Metabolites in Rats, Hamsters, and Guinea Pigs

Haraguchi

Koga²,

Kato³

2004

Drug Metab Dispos

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ABSTRACT:The present study was performed to compare the metabolite profiles of polychlorinated biphenyls (PCBs) in the liver and serum of rats, hamsters, and guinea pigs after exposure to a PCB mixture, Kanechlor 500 (100 mg/kg, i.p.). The percentage of contribution of major PCB residues in the liver 5 days after exposure indicated that nonplanar PCBs with 2,4-or 2,3,4-chlorine substitution were more abundant in the liver in the order rats (43% of total PCBs) > hamsters (20%) > guinea pigs (11%), whereas coplanar PCBs with 4-, 3,4-, or 3,4,5-chlorine substitution were predominant in guinea pigs (61%), followed by hamsters and rats (both 26%). The hepatic concentrations of methylsulfonyl metabolites (MeSO 2 -CBs) were higher in the order guinea pigs > rats > hamsters. Whereas hamsters formed minute amounts of MeSO 2 -CBs from 2,5-dichlorosubstituted PCBs, guinea pigs formed higher levels of metaMeSO 2 -CBs derived from 2,3,6-trichloro-substituted PCBs. In contrast, the serum concentrations of phenolic PCBs were higher in the order hamsters > rats > guinea pigs. Metabolites were predominated by 4-OH-2,3,5,3,4-pentaCB (89% contribution) for rats, 3-OH-2,4,5,2,4-pentaCB (56%) for guinea pigs, and dihydroxylated metabolites (39%) for hamsters. The reduced elimination of coplanar PCBs and the specific distribution of MeSO 2 -and phenolic PCBs may have implications for the differences in sensitivity to PCB toxicity among rats, guinea pigs, and hamsters.

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Mechanism of Biosynthesis of Methylsulfones from PCBs and Related Compounds

Cited by 21 publications

References 28 publications

Can persistent organic pollutants explain the association between serum γ-glutamyltransferase and type 2 diabetes?

Can persistent organic pollutants explain the association between serum γ-glutamyltransferase and type 2 diabetes?

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

Comparative Metabolism of Polychlorinated Biphenyls and Tissue Distribution of Persistent Metabolites in Rats, Hamsters, and Guinea Pigs

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