Search PubMed⌕ Search

Biomedical subjects

D P Hannon

Publications and source records attributed to D P Hannon.

9 recordsLinked to original sources

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. CONCLUSION: The high level of protection provided by FDO indicates that metal chelation is a significant approach to providing photoprotection.

Absorption↗

Time-dependent decrease in sunscreen protection against chronic photodamage in UVB-irradiated hairless mouse skin.

To determine the time dependence of sunscreen protection against chronic photodamage in hairless mice, the time was varied (0-8 h) between topical sunscreen treatment and UVB radiation exposure. Sunscreen products with labeled sun protection factor (SPF) values of 2, 4 and 8 were evaluated; these values were verified in a guinea pig model for SPF determinations. When applied immediately prior to UVB radiation exposure, these sunscreen products were very effective in prevention of skin wrinkling and tumor formation. Onset of photodamage was delayed, the delay being greater with higher SPF values. However, the sunscreen actives were rapidly lost from the skin surface, and their protective effect diminished strikingly as the time between treatment and irradiation increased. For daily protection against chronic photodamage, this suggests a need for photoprotectants with greater substantivity to achieve a high level of protection throughout the day.

Animals↗

Chronic ultraviolet radiation-induced increase in skin iron and the photoprotective effect of topically applied iron chelators.

In the skin of albino hairless mice (Skh:HR-1) there is a basal level of non-heme iron. Chronic exposure of mice to sub-erythemal doses of ultraviolet (UV) B radiation results in an increased skin level of non-heme iron. The iron increase may be the result of a UVB radiation-induced increase in vascular permeability, which we measured in vivo with the dye marker Evans Blue. We also observed greater non-heme iron in sun-exposed vs non-exposed body sites of human skin, suggesting that similar events occur in man. Iron may have a role in skin photodamage by participating in formation of reactive oxygen species. These species have been implicated in skin photodamage. It is known that iron can contribute to oxygen radical production by acting catalytically in the formation of species such as hydroxyl radical. While the basal level of skin iron may be available for catalysis, the elevated iron content of UV-exposed skin increases the potential for iron-catalyzed radical production. Topical application of certain iron chelators to Skh albino hairless mice dramatically delayed the onset of UVB radiation-induced skin photodamage. Non-chelating analogs provided no significant protection.

2,2'-Dipyridyl↗

Photoprotective effect of topical anti-inflammatory agents against ultraviolet radiation-induced chronic skin damage in the hairless mouse.

Albino hairless mice (Skh:HR-1) exposed chronically to suberythemal doses of ultraviolet (UV) radiation display visible and histological alterations in the skin. One alteration is an increase in dermal cellularity, including inflammatory cells. This suggested a role for inflammation in chronic photodamage. We evaluated the photoprotective effect of topical hydrocortisone, ibuprofen, and naproxen against photodamage. All 3 agents protected against UVB radiation-induced visible wrinkling, tumor formation, and histological alterations. Hydrocortisone and naproxen were also evaluated for protection against UVA radiation-induced visible skin sagging and histological alterations. Both were very effective. These data indicate that chronic topical application of anti-inflammatory agents provides broad solar UV spectrum photoprotection.

Administration, Cutaneous↗

Photoprotective effect of superoxide-scavenging antioxidants against ultraviolet radiation-induced chronic skin damage in the hairless mouse.

Albino hairless mice (Skh:HR-1) exposed chronically to suberythemal doses of ultraviolet radiation develop visible skin changes, histological alterations, and tumors. Topical treatment of mice with solutions of superoxide-scavenging antioxidants (such as alpha-tocopherol, ascorbic acid, propyl gallate and Trolox) prior to each UVB radiation exposure reduced significantly the severity of these events. Tocopherol esters and ascorbyl palmitate were not as effective as the parent compounds in providing protection. The data suggest a role for superoxide in UVB radiation-induced skin photoaging and the protective potential of superoxide scavengers. In contrast, the severity of UVA radiation-induced mouse skin damage was not reduced by topical application of the antioxidants tested here.

Animals↗

Wavelength dependence of histological, physical, and visible changes in chronically UV-irradiated hairless mouse skin.

Albino hairless mice (Skh: HR-1) exposed chronically to sub-erythemal doses of UV radiation display physical, visible and histological alterations. Using narrow bandwidth radiation covering the UV radiation spectrum from 280-380 nm, the wavelength dependence of these alterations was determined. The wavelength dependence spectra indicate that for all but one parameter measured (skin sagging), UV-B radiation is considerably more efficient than UV-A radiation in producing changes in the skin. However, in natural sunlight there is considerably more UV-A than UV-B radiation, providing the potential for UV-A to have a larger contribution to skin damage than UV-B. This argues in favor of using broad spectrum photoprotective agents to shield the skin adequately from UV-induced aging. The spectra were also used to develop potential associations among events by determining which events occur at similar wavelengths. There seems to be a correspondence between mouse visible skin wrinking (UV-B event) and two histological events: increase in glycosaminoglycans and alteration in collagen. There was no obvious correspondence among UV-A-induced events.

Animals↗