Redox Cycling of Phenol Induces Oxidative Stress in Human Epidermal Keratinocytes

Details

• Personal Author:
  Castranova, Vincent ; Fabisiak JP ; Jeffries BA ; Kagan VE ; Kommineni C ; Serbinova EA ; Shvedova AA ; Tyurin VA ; Tyurina YY
• Description:
  A variety of phenolic compounds are utilized for industrial production of phenol-formaldehyde resins, paints, lacquers, cosmetics, and pharmaceuticals. Skin exposure to industrial phenolics is known to cause skin rash, dermal inflammation, contact dermatitis, leucoderma, and cancer promotion. The biochemical mechanisms of cytotoxicity of phenolic compounds are not well understood. We hypothesized that enzymatic one-electron oxidation of phenolic compounds resulting in the generation of phenoxyl radicals may be an important contributor to the cytotoxic effects. Phenoxyl radicals are readily reduced by thiols, ascorbate, and other intracellular reductants (e.g., NADH, NADPH) regenerating the parent phenolic compound. Hence, phenolic compounds may undergo enzymatically driven redox-cycling thus causing oxidative stress. To test the hypothesis, we analyzed endogenous thiols, lipid peroxidation, and total antioxidant reserves in normal human keratinocytes exposed to phenol. Using a newly developed cis-parinaric acid-based procedure to assay site-specific oxidative stress in membrane phospholipids, we found that phenol at subtoxic concentrations (50 microM) caused oxidation of phosphatidylcholine and phosphatidylethanolamine (but not of phosphatidylserine) in keratinocytes. Phenol did not induce peroxidation of phospholipids in liposomes prepared from keratinocyte lipids labeled by cis-parinaric acid. Measurements with ThioGlo-1 showed that phenol depleted glutathione but did not produce thiyl radicals as evidenced by our high-performance liquid chromatography measurements of GS.-5, 5-dimethyl1pyrroline N-oxide nitrone. Additionally, phenol caused a significant decrease of protein SH groups. Luminol-enhanced chemiluminescence assay demonstrated a significant decrease in total antioxidant reserves of keratinocytes exposed to phenol. Incubation of ascorbate-preloaded keratinocytes with phenol produced an electron paramagnetic resonance-detectable signal of ascorbate radicals, suggesting that redox-cycling of one-electron oxidation products of phenol, its phenoxyl radicals, is involved in the oxidative effects. As no cytotoxicity was observed in keratinocytes exposed to 50 microM or 500 microM phenol, we conclude that phenol at subtoxic concentrations causes significant oxidative stress. Description provided by NIOSH
• Subjects:
  • Biopharmaceutics
  • Cosmetics
  • Cytotoxins
  • Dermatitis
  • Neoplasms
  • Occupational Health
  • Paint
  • Phenol
  • Safety
  • Skin
  More +
• Keywords:
  • Phenols
  • Phenolic compounds
  • Paints
  • Cosmetics
  • Pharmaceuticals
  • Skin exposure
  • Skin infections
  • Skin disorders
  • Skin diseases
  • Skin irritants
  More +
• ISSN:
  0022-202X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; 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
• Pages in Document:
  354-364
• Volume:
  114
• Issue:
  2
• NIOSHTIC Number:
  nn:20020809
• Citation:
  J Invest Dermatol 2000 Feb; 114(2):354-364
• Contact Point Address:
  Dr. A.A. Shvedova, Health Effects Laboratory Division, Pathology and Physiology Research Branch, NIOSH, 1095 Willowdale Road, Morgantown, WV 26505
• Federal Fiscal Year:
  2000
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Investigative Dermatology
• Download URL:
  https://stacks.cdc.gov/view/cdc/198474/cdc_198474_DS1.pdf
• File Type:
  [PDF - 735.33 KB]
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:52f24cc3c67da130785cd6d60bfc18ca40d6148a700b17ef4bfc48548d42318a005e24edae1bea2719b129768c9d57be6e03671d8d16d7e4cdbb7bfba4c6551a