Bissett D L, Oelrich D M, Hannon D P
Procter & Gamble Company, Miami Valley Laboratories, Cincinnati, OH 45239-8707.
J Am Acad Dermatol. 1994 Oct;31(4):572-8. doi: 10.1016/s0190-9622(94)70218-7.
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).
Our purpose was to determine the level of photoprotection provided by FDO in both animal and human testing.
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.
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.
The high level of protection provided by FDO indicates that metal chelation is a significant approach to providing photoprotection.
在之前的研究中,我们发现铁是皮肤光损伤的一个因素,显然是通过其参与氧自由基的产生。在此我们报告用铁螯合剂2-呋喃二肟(FDO)进行局部光防护。
我们的目的是在动物和人体试验中确定FDO提供的光防护水平。
用5%的FDO单纯赋形剂溶液与赋形剂对小鼠、豚鼠和人类进行局部治疗。然后将皮肤暴露于高于最小红斑量的模拟太阳紫外线辐射剂量下。采集小鼠皮肤用于分析鸟氨酸脱羧酶(ODC);对豚鼠皮肤的红斑进行分级;对人类皮肤的红斑进行分级,并采集活检标本用于分析ODC和进行组织学评估。
在模拟太阳紫外线辐射的动物试验中,局部使用5%的FDO可使无毛小鼠的ODC诱导受到90%的保护,使豚鼠的红斑受到防晒系数为3.5的保护。在一项双盲、配对比较、赋形剂对照的临床试验中,在单次给予三倍最小红斑量的模拟太阳辐射前局部应用5%的FDO可预防紫外线诱导的红斑、晒伤细胞形成、表皮增厚、炎症细胞浸润以及表皮ODC的诱导。
FDO提供的高水平保护表明金属螯合是提供光防护的一种重要方法。