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Identification of novel reaction products of methylene-bis-phenylisocyanate (“MDI”) with oxidized glutathione in aqueous solution and also during incubation of MDI with a murine hepatic S9 fraction
  • Published Date:
    Jul 21 2016
  • Source:
    Toxicol In Vitro. 36:97-104.


Public Access Version Available on: October 01, 2017 information icon
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Details:
  • Pubmed ID:
    27453132
  • Pubmed Central ID:
    PMC5010927
  • Funding:
    R01 OH010941/OH/NIOSH CDC HHS/United States
    R21 OH010438/OH/NIOSH CDC HHS/United States
  • Document Type:
  • Collection(s):
  • Description:
    Methylene diphenyl diisocyanate (MDI) is an important industrial chemical and asthmagenic respiratory sensitizer, however its metabolism remains unclear. In this study we used LC-MS and LC-MS/MS to identify novel reaction products of MDI with oxidized glutathione (GSSG), including an 837m/z [M+H](+) ion corresponding to GSSG bound (via one of its N-termini) to partially hydrolyzed MDI, and an 863m/z [M+H](+) ion corresponding to GSSG cross-linked by MDI (via its two γ-glutamine N-termini). Further studies with heavy isotope labeled and native reduced glutathione (GSH) identified an [M+H](+) ion corresponding to previously described mono(GSH)-MDI, and evidence for "oligomeric" GSH-MDI conjugates. This study also investigated transformational changes in MDI after incubation with an S9 fraction prepared from murine liver. LC-MS analyses of the S9 reaction products revealed the formation of [M+H](+) ions with m/z's and retention times identical to the newly described GSSG-MDI (837 and 863) conjugates and the previously described mono(GSH)-MDI conjugate. Together the data identify novel biological transformations of MDI, which could have implications for exposure-related health effects, and may help target future in vivo studies of metabolism.

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