PMID- 10525276
OWN - NLM
STAT- MEDLINE
DCOM- 20000104
LR  - 20190921
IS  - 0893-228X (Print)
IS  - 0893-228X (Linking)
VI  - 12
IP  - 10
DP  - 1999 Oct
TI  - 5,6-Dihydroxyindoles in the fenton reaction: a model study of the role of melanin 
      precursors in oxidative stress and hyperpigmentary processes.
PG  - 985-92
AB  - Increasing evidence supports the view that diffusible melanin-related metabolites 
      do not serve merely as pigment precursors, but may also act as modulators of the 
      responses of the pigmentary cell melanocyte to external stimuli, especially to 
      inflammation. In this study, the effect of melanin precursors 5, 
      6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) on the 
      Fenton-induced oxidation of deoxyribose was investigated as a model of the 
      oxidative stress processes triggered by the release of iron during inflammation. 
      DHICA caused a powerful inhibition of the H(2)O(2)-Fe(II)/EDTA oxidation under 
      both aerobic and anaerobic conditions, proving to be more efficient than typical 
      hydroxyl radical (HO(*)) scavengers even at low concentrations with respect to 
      deoxyribose. Conversely, DHI in air was a prooxidant at low indole:Fe(II) ratios, 
      but shifted to an antioxidant at higher ratios (>6). The magnitude of the 
      prooxidant effect increased by lowering the pH of the medium or by replacing 
      Fe(II) with Fe(III), but was suppressed by exclusion of oxygen. Both the indoles 
      retained their effects on the Fenton reaction in the absence of EDTA, as a result 
      of their ability to chelate iron ions as evidenced by spectrophotometric 
      experiments. Investigation of the reaction of DHI and DHICA with the Fenton 
      reagent led to the conclusion that the indoles interact efficiently with HO(*), 
      yielding indolesemiquinone species which are then converted to melanin pigments 
      by self-coupling or disproportionation. At low DHI:iron molar ratios, the ability 
      of semiquinones, generated by autoxidation of indoles, to recycle Fe(II) ions 
      prevails, accounting for the observed prooxidant effect. Collectively, the 
      results of this study provide new evidence for melanogenic 5,6-dihydroxyindoles 
      as a novel class of biological antioxidants and point to these compounds as the 
      key to interpreting the response of melanocytes to oxidative injuries. Moreover, 
      the rapid formation of melanin following the exposure of 5, 6-dihydroxyindoles to 
      the Fenton oxidation suggests new mechanisms of skin hyperpigmentation associated 
      with inflammation.
FAU - Novellino, L
AU  - Novellino L
AD  - Department of Organic and Biological Chemistry, University of Naples "Federico 
      II", Via Mezzocannone 16, I-80134 Naples, Italy.
FAU - Napolitano, A
AU  - Napolitano A
FAU - Prota, G
AU  - Prota G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (Chelating Agents)
RN  - 0 (Indoles)
RN  - 0 (Melanins)
RN  - 0 (Pigments, Biological)
RN  - 142M471B3J (Carbon Dioxide)
RN  - 3352-57-6 (Hydroxyl Radical)
RN  - 4790-08-3 (5,6-dihydroxy-2-indolylcarboxylic acid)
RN  - 533-67-5 (Deoxyribose)
RN  - 634-97-9 (2-pyrrolecarboxylic acid)
RN  - 9DLQ4CIU6V (Proline)
RN  - 9G34HU7RV0 (Edetic Acid)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - E1UOL152H7 (Iron)
RN  - Z3OC8499KG (5,6-dihydroxyindole)
SB  - IM
MH  - Carbon Dioxide/chemistry
MH  - Chelating Agents/chemistry
MH  - Deoxyribose/chemistry
MH  - Edetic Acid/chemistry
MH  - Hydrogen Peroxide/chemistry
MH  - Hydroxyl Radical
MH  - Hyperpigmentation/*metabolism
MH  - Indoles/*chemistry
MH  - Iron/chemistry
MH  - Melanins/chemistry/*metabolism
MH  - Models, Biological
MH  - Oxidative Stress/*physiology
MH  - Pigments, Biological/chemistry
MH  - Proline/analogs & derivatives/chemistry
EDAT- 1999/10/20 00:00
MHDA- 1999/10/20 00:01
CRDT- 1999/10/20 00:00
PHST- 1999/10/20 00:00 [pubmed]
PHST- 1999/10/20 00:01 [medline]
PHST- 1999/10/20 00:00 [entrez]
AID - tx990020i [pii]
AID - 10.1021/tx990020i [doi]
PST - ppublish
SO  - Chem Res Toxicol. 1999 Oct;12(10):985-92. doi: 10.1021/tx990020i.