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

Details

• Alternative Title:
  Toxicol In Vitro
• Personal Author:
  Wisnewski, AV ; Liu, J ; Nassar, AF
• 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-glutamate N-termini) [corrected]. 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.
• Subjects:
  Allergens Animals Glutathione Glutathione Disulfide Isocyanates Liver Male Mice, Inbred C57BL Solutions
• Source:
  Toxicol In Vitro. 36:97-104
• Pubmed ID:
  27453132
• Pubmed Central ID:
  PMC5010927
• Document Type:
  Journal Article
• Funding:
  R01 OH010941/OH/NIOSH CDC HHSUnited States/ ; R01OH010941/ACL HHSUnited States/ ; R21 OH010438/OH/NIOSH CDC HHSUnited States/
• Volume:
  36
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:c15df76af7f0c2da333649619b25347f8da9c239e8ddba3cba88b652498896f5
• Download URL:
  https://stacks.cdc.gov/view/cdc/41197/cdc_41197_DS1.pdf
• File Type:
  [PDF - 967.95 KB ]