Oxidative Stress and Cytotoxicity of Phenol and AMVN in Human Keratinocytes: Evidence for Enhanced Lipid and Thiol Oxidation and Antioxidant Depletion

Details

• Personal Author:
  Castranova, Vincent ; Kagan VE ; Kommineni C ; Shvedova AA ; Tyurin VA ; Tyurina YY
• Description:
  A variety of phenolic compounds that are utilized in industry (e.g., for production of phenol-formaldehyde resins, paints and lacquers, cosmetics and pharmaceuticals) are toxic to skin (i.e., may cause rashy dermal inflammation, contact dermatitis, leucoderma, or 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 generation of phenoxyl radicals may be an important contributor to their cytotoxic effects. Phenoxyl radicals are readily reduced (regenerated) by thiols, ascorbate and other intracellular reductants (e.g., NADH or NADPH). Hence, phenolic compounds may undergo enzymatically-driven redox-cycling, thus causing oxidative stress. To experimentally test the hypothesis, we performed measurements of thiols, lipid peroxidation and total antioxidant reserves in normal human keratinocytes incubated with phenol and compared the effects to those produced by an azo-initiator of peroxyl radicals, AMVN, 2,2' -azobis(2,4-dimethylvaleronitrile). 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 and 500 microM) caused oxidation of phosphatidylcholine and phosphatidylethanolamine (but not of phosphatidylserine) in keratinocytes. The magnitude of the phenol-induced changes in phospholipids was quantitatively comparable to those induced by AMVN. Measurements with ThioGlo showed that phenol dramatically depleted GSH. 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 EPR-detectable signal of ascorbate radicals. We conclude that redoxcycling of the one-electron oxidation product of phenol, its phenoxylradical, is involved in the oxidative cytotoxic effects. [Description provided by NIOSH]
• Subjects:
  Chemistry Chemistry, Analytic Cytotoxins Dermatitis Hypersensitivity Occupational Health Phenol Safety Skin Skin Diseases
• Keywords:
  Allergic-dermatitis Allergic-reactions Analytical-chemistry Analytical-processes Contact-allergies Contact-dermatitis Cytotoxic-effects Cytotoxicity Phenolic-compounds Phenols Statistical-analysis

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• Document Type:
  Text
• Genre:
  Abstract or Summary ; Proceedings
• Place as Subject:
  New Jersey ; OSHA Region 2 ; OSHA Region 3 ; 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:
  1
• NIOSHTIC Number:
  nn:20028185
• Citation:
  Proceedings of the Advances in the Biology and Treatment of the Skin Symposium, Piscataway, NJ, June 23-25, 1999. Piscataway, NJ: Environmental and Occupational Health Sciences Institute, 1999 Jun; :1
• Federal Fiscal Year:
  1999
• Peer Reviewed:
  False
• Source Full Name:
  Proceedings of the Advances in the Biology and Treatment of the Skin Symposium, Piscataway, NJ, June 23-25, 1999
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e28527f95462824aa0d052752d00aa0a7426fb10ca0b0fa92a3aa1c2ab9b9ccfb5819ba529ac59b78a2e8201ab696707e6d2a4463d3f23c3f2f1c594cf4aeb55
• Download URL:
  https://stacks.cdc.gov/view/cdc/189804/cdc_189804_DS1.pdf
• File Type:
  [PDF - 321.15 KB ]