Evaluation of a topical iron chelator in animals and in human beings: short-term photoprotection by 2-furildioxime.
BACKGROUND
In previous work we found that iron is a factor in skin photodamage, apparently by way of its participation in oxygen radical production. Here we report topical photoprotection with the iron chelator 2-furildioxime (FDO).


OBJECTIVE
Our purpose was to determine the level of photoprotection provided by FDO in both animal and human testing.


METHODS
Mice, guinea pigs, and human beings were treated topically with 5% simple vehicle solutions of FDO versus vehicle. The skin was then exposed to doses of simulated solar UV radiation greater than the minimal erythema dose. Mouse skin was harvested for analysis of ornithine decarboxylase (ODC); guinea pig skin was graded for erythema; and human skin was graded for erythema and biopsy specimens taken for analysis of ODC and for histologic evaluation.


RESULTS
In animal testing with simulated solar UV radiation, topical 5% FDO provided 90% protection against induction of ODC in the hairless mouse and sun protection factor 3.5 against erythema in the guinea pig. In a double-blind, paired-comparison, vehicle-controlled clinical test, 5% FDO applied topically before a single dose of simulated solar radiation at three times minimal erythema dose prevented UV-induced erythema, sunburn cell formation, epidermal thickening, infiltration of inflammatory cells, and induction of epidermal ODC.


CONCLUSIONS
The high level of protection provided by FDO indicates that metal chelation is a significant approach to providing photoprotection.
Bissett
D L
DL
Procter & Gamble Company, Miami Valley Laboratories, Cincinnati, OH 45239-8707.
Oelrich
D M
DM
Hannon
D P
DP
D000042:Absorption; D000279:Administration, Cutaneous; D000328:Adult; D000818:Animals; D004311:Double-Blind Method; D004341:Drug Evaluation; D004890:Erythema / Q000473:pathology; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007502:Iron Chelating Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D008815:Mice, Inbred Strains; D009955:Ornithine Decarboxylase / Q000032:analysis; D010091:Oximes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D014677:Pharmaceutical Vehicles; D011829:Radiation Dosage; D012867:Skin / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D015595:Skin Aging / Q000187:drug effects* / Q000528:radiation effects*; D013471:Sunburn / Q000473:pathology / Q000517:prevention & control; D013473:Sunscreening Agents / Q000494:pharmacology*; D014466:Ultraviolet Rays
D007502:Iron Chelating Agents; D010091:Oximes; D014677:Pharmaceutical Vehicles; D013473:Sunscreening Agents; C014565:furildioxime; D009955:Ornithine Decarboxylase