Combination of Phenolic Compounds With Arachidonic Acid Induces “Futile Thiol Pumping” and Oxidative Stress in Epidermal Human Keratinocytes

Details

• Personal Author:
  Castranova, Vincent ; Jeffries B ; Kagan VE ; Kommineni C ; Shvedova AA ; Tyurin VA ; Tyurina YY
• Description:
  In human epidermis, active metabolism of arachidonic acid to prostaglandins is regulated by prostaglandin H synthase (PHS) which is also known to catalyze xenobiotic biotransformation. In particular, peroxidase activity of PHS may catalyze one-electron oxidation of phenolic compounds to their phenoxyl radicals. The phenoxyl radical may attack intracellular thiols to regenerate the phenolic compound that may repeatedly undergo peroxidase-catalyzed oxidation. This thiol-supported redox-cycling of phenolic compounds (i.e., "futile thiol pumping") has been demonstrated in keratinocytes exposed to acetaminophen (Mason et al., 1989). In the present work, we tested whether redox-cycling of phenolic compounds can induce peroxidation of membrane phospholipids and deplete antioxidants in keratinocytes. We used a fluorescence HPLC assay for quantitation of membrane phospholipids metabolically prelabelled with oxidation-sensitive natural fluorescent fatty acid, cis-parinaric acid (PnA). We found that a combination of phenol/arachidpnic acid or cresol/rachidonic acid caused a pronounced oxidation of major phospholipids: phosphatidytcholine, phosphatidylethanolamine, and phosphatidylserine in keratinocytes. Exposure to phenol (cresol) + arachidonic acid decreased total antioxidant reserves in keratinocytes as measured by luminol-enhanced chemiluminescence in the presence of a water-soluble azo-initiator, AAPH. Measurements with a thiol-reagent, ThioGlo-1 showed that phenol (cresol) + arachidonic acid depleted GSH and oxidized protein sulfuydryls in keratinocytes. Electron microscopy revealed characteristic apoptotic nuclear fragmentation in keratinocytes exposed to a combination of phenolic compounds with arachidonic acid. These results suggest that peroxidase activity of PHS may be involved in phenol (cresol)-induced "futile thiol pumping" in human epidermal keratinocytes. [Description provided by NIOSH]
• Subjects:
  Environmental Monitoring Epidemiology Occupational Health Phenol Safety Skin Skin Diseases Sulfhydryl Compounds
• Keywords:
  Exposure-assessment Phenolic-acids Phenolic-compounds Phenols Skin-disorders Skin-exposure Skin-sensitivity Skin-tests Statistical-analysis Thiols
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Louisiana ; OSHA Region 3 ; OSHA Region 6 ; Pennsylvania ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  48
• NIOSHTIC Number:
  nn:20027966
• Citation:
  Toxicologist 1999 Mar; 48(1-S):205
• Federal Fiscal Year:
  1999
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 38th Annual Meeting, March 14-18, 1999, New Orleans, Louisiana
• Supplement:
  1-S
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e97265e6842163253e68759fdbb49c796c3cf0535da93c730cb70ee0f46dbb2c935c1d1ca75230751301e3ef012a5747bd23bbdd2f091929fa21267558242a1e
• Download URL:
  https://stacks.cdc.gov/view/cdc/189702/cdc_189702_DS1.pdf
• File Type:
  [PDF - 146.39 KB ]