Search

Lycopene, an acyclic hydrocarbon, non-provitamin A carotenoid, is a potent antioxidant with well-documented anticancer properties. In this study, we investigated the effects of dietary lycopene on sub-acute and chronic ultraviolet B (UVB)-induced skin carcinogenesis in SKH-1 mice. Groups of three mice were fed with a nonsupplemented or 1% lycopene diet for two weeks before and throughout two weeks of UVB irradiation (30 mJ/cm2 UVB, thrice weekly). The lycopene diet significantly reduced the formation of pyrimidine dimers (PDs) and the expression of proliferative cellular nuclear antigen (PCNA) in UVB-irradiated skin. Then groups of eighteen mice were each fed with control diet or with a 0.25% or 1% (w/w) lycopene-supplemented diet for 40 weeks, beginning one week before UVB irradiation (30 mJ/cm2 UVB, thrice weekly for 23 weeks) and continuing after termination of UVB. Lycopene significantly inhibited the onset and decreased the incidence, multiplicity, and tumor weights of UVB-induced skin tumors. UVB-induced epidermal hyperplasia and PCNA expression were still remarkably inhibited by dietary lycopene, even up to 40 weeks. No significant difference in protection was detected between the low and high concentrations of lycopene. These results demonstrate that dietary lycopene does protect against UVB-induced epidermal hyperplasia and carcinogenesis. J Drugs Dermatol. 2019;18(12):1244-1254.

Skin is an efficient protective barrier armed with an intricate network of antioxidants. External environmental stress diminishes and sometimes overwhelms these innate protective mechanisms; aging slows their efficacy. Topical antioxidants enhance natural endogenous defenses to create an indwelling reservoir for sustained protection with far higher concentrations than possible with oral intake. The challenge is creating formulations of these labile molecules that are stable, active, and can be effectively absorbed transdermally to deliver high concentrations.

Recent research has given us new insights into the molecular biology of extrinsic aging of the skin. Not only does UV irradiation directly cause photoaging of the skin, but also environmental pollutants significantly damage exposed skin by several mechanisms. Exposure to the noxious gases of air pollution with simultaneous exposure to UVA can act synergistically to initiate skin cancer. Also ozone generated from pollutants reacting with UV induces oxidative stress of the skin's surface via formation of lipid peroxidation products, with cascading consequences to deeper layers. Furthermore, new studies have demonstrated that particulate matter (PM) pollutants can penetrate the skin transepidermally and through hair follicles to induce skin aging via the aryl hydrocarbon receptor (AHR), a recently discovered ligand-activated transcription factor that regulates and protects keratinocytes, melanocytes, and fibroblasts. With this understanding that extrinsic aging of the skin is not only due to photoaging, we realize the necessity of protection beyond sunscreen. Fortunately, correctly formulated topical antioxidants can prevent damage inflicted by both UV and environmental pollution.

Although many cosmeceutical formulations contain vitamin C and/or vitamin E, very few are actually effective in topical application. First because there is only a low concentration, second because the stability is compromised as soon as the product is opened and exposed to air and light, and third because the form of the molecule (an ester or a mixture of isomers) is not absorbed or metabolized effectively by the skin. However, when a stable formulation delivers a high concentration of the nonesterified, optimal isomer of the antioxidant, vitamins C and E do indeed inhibit the acute ultraviolet (UV) damage of erythema, sunburn, and tanning as well as chronic UV photoaging and skin cancer. Both are highly effective depigmenting agents. Topical vitamin C also increases collagen synthesis in both young and old fibroblasts. Because vitamin C regenerates oxidized vitamin E, the combination in a cosmeceutical formulation is synergistic – particularly in UV protection.

Previous studies in mice have shown that topical L-selenomethionine (SeMet) can prevent UVB-induced skin cancer when applied continuously before, during, and after the radiation exposure. With topical application of SeMet, selenium levels were shown to increase in the skin and liver, as well as in tumor tissue. Thus, possibly, the timing of SeMet application could affect the degree of inhibition of UVB-tumorigenesis (or maybe even enhance tumorigenesis at some stage). The goal of this research was to determine whether topical SeMet best inhibits UV-induced skin cancer if (a) begun before and continued during and after UVB exposure, (b) if begun before UVB-exposure and discontinued when tumors are first clinically detected, or (c) if begun only after tumors are first detected and continued thereafter. Groups of ten Skh: 1 hairless, non-pigmented mice were treated topically with vehicle lotion, or with SeMet (0.05%) in that vehicle lotion applied either (a) before, during, and after UV exposure, (b) before UV radiation and continued only until the first tumor was detected, or (c) only after the first tumor was detected. In all cases, UV irradiation was discontinued at the time of detection of the first tumor. Optimal inhibition of skin cancer was achieved by application of topical SeMet before, during, and after exposure; significant protection was also attained with application only after the onset of tumors. Notably, statistically significant protection was not seen with SeMet application only prior to tumor detection. These results suggest that even beginning SeMet supplementation late in the process of tumorigenesis can help protect from UV-induced photodamage and skin cancer.

Adipose tissue was obtained from six women undergoing liposuction twice at 6-mo intervals. Samples obtained bilaterally from abdomen, inner thigh, and outer thigh had fatty acids quantified by gas chromatography. There were no important differences between sides or over time. The saturates 14:0, 16:0, 18:0, and 20:0 were higher in abdominal adipose than in outer thigh (P < 0.002 for all); 16:1 and 18:1 omega 9 were lower in abdomen vs outer thigh (P < 0.01), whereas 18:1 omega 7 and 20:1 omega 9 were unchanged. Polyunsaturates 18:2 omega 6, 20:3 omega 6, and 20:4 omega 6 were higher in outer thigh than in abdomen (P < 0.06), and inner thigh values were intermediate. These changes in fatty acid composition resulted in lower mean triglyceride melting points from abdomen to inner thigh to outer thigh, and suggest that temperature may influence the selection process determining the variation in adipose fatty acid composition with anatomical location. Because the site-specific differences included essential fatty acids, selective uptake as well as potential differences in in situ fatty acid modification are indicated.

Publisher Summary This chapter describes some of the most effective, scientifically proven formulations to revitalize aging skin. There are two great advantages to applying an active formulation of topical antioxidants to the skin. First, the skin attains far higher levels of each antioxidant than can be achieved by only taking these supplements orally. For example, the level of vitamin C attained in the skin by topical application is 20–40 times the level achievable with oral vitamin C. With topical application, the concentration of vitamin E increases by a factor of 10.6 and selenium, by a factor of 1.7. While sunscreens are still mainstay for protecting skin from photodamage, they are not enough. Because most of us actually apply only about one-fourth of the amount of sunscreen needed to give the designated SPF. Frequent application is absolutely necessary even for “highly water-resistant” formulations because sunscreen is washed off not only by swimming and sweating, but also by imperceptible perspiration. Furthermore, while sunscreens reduce UV-induced erythema and the DNA damage of 8-OHdG and thymine dimer, they only block about 55 percent of the free radical production. This protection over time not only protects the skin by diminishing the ongoing free radical insult and inflammation, but also reverses the unattractive appearance of previous photodamage by directly enhancing collagen synthesis and elastic tissue repair.

Although many cosmeceutical formulations contain vitamin C and/or vitamin E, very few are actually effective in topical application. First because there is only a low concentration, second because the stability is compromised as soon as the product is opened and exposed to air and light, and third because the form of the molecule (an ester or a mixture of isomers) is not absorbed or metabolized effectively by the skin. However, when a stable formulation delivers a high concentration of the nonesterified, optimal isomer of the antioxidant, vitamins C and E do indeed inhibit the acute ultraviolet (UV) damage of erythema, sunburn, and tanning as well as chronic UV photoaging and skin cancer. Both are highly effective depigmenting agents. Topical vitamin C also increases collagen synthesis in both young and old fibroblasts. Because vitamin C regenerates oxidized vitamin E, the combination in a cosmeceutical formulation is synergistic - particularly in UV protection.

Background The antioxidants selenium and vitamin E can be effective in reducing acute and chronic ultraviolet (UV)-induced skin damage. Objective This study investigated whether topical l-selenomethionine with topical RRR-α-tocopherol (Eol) or oral RRR-α-tocopheryl acetate (Eac) can reduce the incidence of UV-induced skin damage more than treatment with each alone. Methods Skh:2 hairless pigmented mice were treated with lotion vehicle, l-selenomethionine lotion, Eol lotion, oral Eac, l-selenomethionine plus Eol lotion, or l-selenomethionine lotion plus oral Eac and exposed to UVB. Skin pigmentation was scored, and the number of skin tumors per animal was counted weekly. Results Mice treated with selenium and vitamin E had significantly less acute and chronic UV-induced skin damage. Conclusion Topical l-selenomethionine alone and combined with vitamin E gave the best protection against UV-induced blistering and pigmentation. In protecting against skin cancer, topical Eol and topical l-selenomethionine plus oral Eac were best. Significant synergy of l-selenomethionine with vitamin E was not observed.

This study investigates whether supplementation with topical RRR-alpha-tocopherol (Eol), topical RRR-alpha-tocopheryl succinate, and oral RRR-alpha-tocopheryl acetate can reduce the incidence of acute and chronic damage to the skin (i.e., sunburn and pigmentation and skin cancer, respectively) induced by ultraviolet (UV) irradiation to mice. Groups of twenty Skh:2 female hairless pigmented mice were treated with 1) lotion vehicle, 2) 5% Eol lotion, 3) 5% topical RRR-alpha-tocopheryl succinate lotion, or 4) lotion vehicle and oral RRR-alpha-tocopheryl acetate. Within each group, 15 mice were exposed to 0.24 J/cm2 of UV-B radiation three times per week. The animals' weights and food intakes were monitored, and the vitamin E concentrations of skin, liver, and adipose tissue were measured to determine whether the topical Eol resulted in significant tissue levels. Skin pigmentation was scored, and the total number of clinically detectable skin tumors per animal was counted weekly. Results showed that the skin concentrations of Eol, as well as levels in the adipose tissue, were increased after topical application. Mice treated with each form of vitamin E showed no signs of toxicity and had significantly less acute and chronic skin damage induced by UV irradiation, as indicated by reduced inflammation and pigmentation and by later onset and lesser incidence of skin cancer.

This study was conducted to determine whether oral and/or topical selenium (Se) supplementation can reduce the incidence of acute and/or chronic damage to the skin (i.e., sunburn and pigmentation and/or skin cancer, respectively) induced by ultraviolet (UV) irradiation in mice. Groups of 38 BALB:c female mice or 16 Skh:2 hairless pigmented mice were treated with 1) lotion vehicle, 2) 0.02% L-selenomethionine (SeMet) lotion, or 3) vehicle and 1.5 ppm SeMet in the drinking water. Within each group, 30 BALB:c mice or 12 Skh:2 mice were given UV irradiation (Westinghouse FS 40 bulbs) three times per week in doses of 0.575 and 0.24 J/cm2, respectively. The animals' weights and food intakes and the Se concentrations of skin and liver were measured. Skin biopsies were taken from the backs and abdomens of all animals to evaluate the relative amounts of Se and the damage by UV irradiation. Skin pigmentation was scored, and the total number of clinically detectable skin tumors per animal was counted weekly. Results showed that the skin Se concentrations in areas of application of the lotion containing SeMet were greater than those of animals given comparable oral doses, while the Se concentrations of untreated skin and liver were similar to those of animals receiving oral Se. Mice treated with Se showed no signs of toxicity and had significantly less skin damage by UV irradiation, as indicated by reduced inflammation and pigmentation and by later onset and lesser incidence of skin cancer.

There is no way to age without getting wrinkles. However, patients can be taught how to retard the onset of wrinkles by avoiding unprotected sun exposure, unnecessary facial movements, and certain sleeping positions. Relatively simple non-surgical techniques are available for correction of wrinkles. Small wrinkles can be treated with exfoliation, topical tretinoin (Retin-A), or topical alpha hydroxy acids. Large wrinkles can be improved with implantation of bovine collagen, silicone, or fat extracted from the abdomen or thigh of the patient. Each method is effective when used for the correct indications.

It has previously been demonstrated with sequential biopsies analyzed by standard histological stains, immunofluorescence, and electron microscopy that an injectable form of type I bovine dermal collagen (Zyderm® Collagen Implant, or ZCI) in the human dermis stimulates a host response. This host response results in implant degradation and replacement by newly generated host collagen. However, definitive proof that the human collagen is deposited directly on the bovine collagen implants is lacking. This study reports for the first time simultaneous labeling of the ZCI with fluorescein and the host collagen type III with rhodamine. These experiments show that human collagen type III is synthesized directly on the bovine collagen implants.

The histological fate of an injectable form of type I bovine dermal collagen (Zyderm collagen implant) in the human dermis and subcutaneous tissue has been studied. Sequential biopsies were analyzed by hematoxylin-eosin and Weigert's stains, by immunofluorescence (using a highly specific rabbit anti-Zyderm collagen antibody and a specific anti-human type III collagen antibody), and by electron miscroscopy. The results of this study suggest that the bovine implant material stimulates a host response resulting in implant degradation and replacement by newly generated host collagen.

The histologic fate of an injectable form of type I bovine dermal collagen (Zyderm Collagen Implant, ZCI) in the pig dermis and subcutaneous tissue has been studied. Biopsies were taken sequentially and analyzed by hematoxylin and eosin (H&E) and Weigert's stain, by birefringence, by direct immunofluorescence (using a highly specific rabbit anti-Zyderm antibody), and by electron microscopy. The implant material was found to stimulate a host response resulting in implant degradation and replacement by newly generated host collagen.