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Sunscreens Promote Repair of Ultraviolet Radiation-Induced Dermal Damage
Abstract
Chronic UV irradiation profoundly damages the dermis of human and animal skin. These alterations were thought to be irreversible. Recently, we showed that substantial repair occurred in hairless mice after stopping UV exposure. A band of new connective tissue was laid down subepidermally. The present study focussed on whether repair would occur if animals were protected by sunscreens after dermal damage was induced and irradiation was continued. Albino hairless mice were exposed to Westinghouse FS20 sunlamps thrice weekly for 30 weeks. The daily dose of UV (UVB + UVA) was 0.17 J/cm2. Sunscreens of sun protection factors (SPF) 6 and 15 were applied after 10 and 20 weeks of irradiation. Biopsies were taken at 10, 20, 30, and 45 weeks of the experiment. With both sunscreens, especially SPF-15, previously damaged dermis was repaired during continued irradiation. Repair occurred in situ and, in severely damaged skin, in the novel form of subepidermal reconstruction zones of new connective tissue with parallel collagen bundles and a network of fine elastic fibers.
... The first use of the hairless mouse to examine the multiple histologic aspects of photoaging was by Kligman et al. (1982). In a study that included an assessment of the protective effects of low and high sun protection factor (SPF) sunscreens, both the Skh-1 and Skh-2 were irradiated mainly with UV-B (Westinghouse FS tubes; peak 313 nm). ...
... As in humans, wrinkles were induced by the UV exposures, TEWL increased and the microtopograhy, assessed with skin replicas, was modified. Confirming the work of Kligman et al. (1982 Kligman et al. ( , 1985 ), elastosis and histologic changes in collagen were reported although to a lesser degree than in the earlier studies. The differences are probably attributable to the lower UV dose and the different strain of mice used by Fourtanier et al. ...
... Histologic changes in the Bissett et al. (1987) study were mainly in agreement with those reported by the previous workers. As in the Fourtanier et al. study (1986), changes were less severe than those reported by Kligman et al. (1982 Kligman et al. ( , 1985). In this case, since the mice were of the same strain, the differences were probably dose related. ...
... Photoaging was considered irreversible for centuries until Kligman et al. found it partially reversible in hairless mice [1]. Since then, efforts have been undertaken to reverse photoaging using retinoic acid and topical/systemic natural antioxidants [2,3]. ...
... LIOB appears as a dark, hypo-reflective vacuole (star) in the epidermis, detected by real-time OCT images. UVA-L(+) group: (b) immediately and (c) 120 h after the initial laser treatment, (d)1 week, and (e) 3 weeks after the third laser treatment. Microscopic epidermal necrotic debris (MENDS) was observed as a hyper-reflective stack immediately inferior to and within the stratum corneum (yellow arrow). ...
Although nude mice are an ideal photoaging research model, skin biopsies result in inflammation and are rarely performed at baseline. Meanwhile, studies on antiphotoaging antioxidants or rejuvenation techniques often neglect the spontaneous reversal capacity. Full-field optical coherence tomography (FFOCT) can acquire cellular details noninvasively. This study aimed to establish a photoaging and sequential function reversal nude mice model assisted by an in vivo cellular resolution FFOCT system. We investigated whether a picosecond alexandrite laser (PAL) with a diffractive lens array (DLA) accelerated the reversal. In the sequential noninvasive assessment using FFOCT, a spectrophotometer, and DermaLab Combo®, the photodamage percentage recovery plot demonstrated the spontaneous recovery capacity of the affected skin by UVB-induced transepidermal water loss and UVA-induced epidermis thickening. A PAL with DLA not only accelerated skin barrier regeneration with epidermal polarity, but also increased dermal neocollagenesis, whereas the nonlasered group still had >60% collagen intensity loss and 40% erythema from photodamage. Our study demonstrated that FFOCT images accurately resemble the living tissue. The photoaging and sequential function reversal model provides a reference to assess the spontaneous recovery capacity of nude mice from photodamage. This model can be utilized to evaluate the sequential noninvasive photodamage and reversal effects after other interventions.
... 6,7,8 However, the majority of clinical research on photoprotection has been conducted on subjects with Fitzpatrick types I to III skin and have reported improvements in signs associated with skin aging and texture. 9,10 Verschoore et al was the first to conduct a short-term doi: 10.36849/JDD.2020.4836 To order reprints or e-prints of JDD articles please contact sales@jddonline.com ...
... Overall, the study demonstrates that daily use of sunscreen can protect skin from photo related damage and even reverse some of the photo-damage that has already occurred in skin. In addition to previous studies that demonstrated the photo-protective properties of sunscreen use in normal and diseased skin states 7,8,9,10 and in view of the fact that good photoprotection behaviors are not common among Hispanics, 14,15,16 studies of this type can help educate and stress the importance of daily use of sunscreen and other sun protection behaviors in Hispanic and other skin of color populations. ...
aThe Vitiligo and Pigmentation Institute of Southern California, Los Angeles, CA bDepartment of Dermatology, Howard University, Washington, DC cL’Oreal Research and Innovation, Paris, France dL’Oreal Research and Innovation, Clark, NJ.
... We applied the spidroin extract using a spray bottle by covering the whole worm body. Each group received irradiation for 15 min per day, 30 min per day, and 1 h per each group for three days and three container replicates per group (Kligman et al. 1983;Häkkinen and Oikari 2004). UVR-A effects were observed in plastic containers (20 cm * 20 cm) containing 2 mm buffered saline (0.01 M, pH 7.4) or moist filter paper with buffered saline. ...
Numerous studies have confirmed the damage caused by excessive exposure to ultraviolet-A rays. Malignant melanoma and skin cancer are two of the most serious health consequences. Thus, the UV-A protectant is intended to protect the skin, especially the two primary layers of skin (epidermis that represents the interface between the body and its surroundings and dermis). Spider silk is the most powerful natural fibre due to its regeneration, biocompatibility, antimicrobial, wound healing, antiseptic, and blood clotting properties. This work targeted to determine the protective effect of spidroin extract against UV-A radiation damage. Earthworms Aporrectodea caliginosa were collected from Assiut University’s farm. Each set of ten earthworms was separated into six groups and placed in a plastic container. Webs of spiders collected from trees and old houses. Spidroin was extracted and utilised in this work to determine the potential effects of topical application on UV-A protection. The experiment is divided into two sections: (1) UV-A exposure and (2) the use of spidroin extract to protect the earthworms from ultraviolet radiation. Two control groups (1،2) of worms were not received UV-A exposure, and four groups (3,4,5,6) were exposed to UVR-A. In contrast, groups (5,6) were received spidroin extract before exposure to UV-A. Each group from the groups (3,4,5,6) was exposed for three consecutive days (¼ hour/day, ½ hour/day, and 1 h/day), using a UV-Lamp with a wavelength of 366 nm. The histopathological changes revealed that after 1⁄4 h of UV exposure, the cuticle was swollen with a slightly detached epithelium. The cuticle was down after 1⁄2 h of exposure, and the epidermis was totally damaged and necrosed. After 1 h, the exposure showed destruction of the epidermis in the circular muscle with a loss of muscle filament integrity, varying size, and altered nucleus form, along with mild disintegration of longitudinal muscle. Spidroin extract is critical for earthworm protection against UV-A radiation damage and able to regeneration. For the first time, morphological and histological analysis was established to detect the Spidroin extract evaluated for topical application on earthworms. Earthworms can be considered as a robust human skin model prior to UV-A exposure. It induces a complete protective effect against UV-A radiation damage in earthworms.
Graphical abstract
... In studies using hairless mice as well as people, skin morphological changes caused by long-term repeated UV irradiation were reported to be prevented by applying SPF 15 sunscreen. 4,16,17,18 In addition, regarding the preventive effects of long-term clinical sunscreen on photoaging, a study using a sunscreen of SPF 16 showed its efficacy. 6,7 The Skin Cancer Foundation in the United States gives recommendation stickers to sunscreens that meet criteria such as SPF15 or higher. ...
Background
Sun protection factor (SPF) and UVA protection factor (UVAPF) are performance indicators consumers recognize for UV protective cosmetics such as sunscreens. However, on-site application density affects actual UV protection, despite these indicators. To understand actual UV protection better, a more reliable manner is needed to verify application density for further discussion of photoprotection efficacy regarding public health.
Method
The subjects applied the SPF-labeled sunscreens as usual. We measured the application amount and area including any amount on their hands to calculate the average application density on the face. Also, sunscreens were applied at densities of 0.5, 1.0, and 2.0 mg/cm². The SPF values were measured at each application site to evaluate the effect of application density on photoprotection efficacy.
Result
We established a method of measuring application density utilizing three-dimensional photograph analysis. The median application density of the sunscreen applied in actual use was 1.33 mg/cm². The measured SPF values decreased in association with the decreased application density of sunscreens. Based on the estimate assuming the first-order correlation, the SPF value required to get the protective effect equivalent to a sunscreen with SPF 15, 30, or 50 at 2 mg/cm² was calculated to be 23.8, 47.5, and 79.2 respectively with the application density of 1.33 mg/cm².
Conclusion
We demonstrated a reasonable procedure for estimating the photoprotection efficacy of sunscreens on the face. A suggestion was made to consider the application density for further discussion of photoprotection among consumers, especially for the long term with respect to public health.
... Furthermore, recent advances in the field of aesthetic and anti-aging medicine have also demonstrated that UVinduced photoaging is manifested primarily as reduction in skin elasticity, 2,4,6,37 and that the loss of integrity of elastic fibers directly leads to the marked reduction of skin elasticity and the formation of sagging skin. 2,4,5,[43][44][45] In this study, it was found that when mouse skin was exposed under UV for 10 weeks, it exhibited an obviously extended recovery time in the pinch test (indicating visible reduction in skin elasticity), and the normal fibrillary pattern of skin elastic fibers was replaced by large quantities of thickened, tangled, degraded, and non-functional fibers. However, HSYA treatment (100-200 lg/mouse) markedly shortened the recovery time and reversed the disrupted elastic fibers caused by UV, strongly revealing that HSYA had the potential to maintain the integrity of dermal elastic fibers, and could further attenuate chronic UV-induced skin sagging and reduction of elasticity. ...
Chronic exposure to ultraviolet (UV) irradiation is believed to be the major cause of skin damage that resulting premature aging of the skin, so called photo-aging, characterized by increases in skin thickness, formation of wrinkle, and loss of skin elasticity. UV induces damage to skin mainly by oxidative stress and collagen degradation. In this study, we examined the photoprotective effect of Hydroxysafflor yellow A (HSYA), a major active chemical component isolated from Carthamus tinctorius L., by topical application on the skin of mice. Exposure of the dorsal depilated skin of mice to UV radiation four times a week for 10 weeks induced epidermal hyperplasia, elastin accumulation, collagen degradation, etc. HSYA at the doses of 50, 100 and 200μg/mouse was topically applied immediately following each UV exposure. The effects of HSYA were evaluated by a series of test, including macroscopic and histopathological evaluation of skin, pinch test, and redox homeostasis of skin homogenates. Results showed that the UV-induced skin damages were significantly recovered after HSYA treatment, especially at doses of 100 and 200μg/mouse. This protective effect is possibly related to the anti-oxidative property of HSYA and mediated by promoting endogenous collagen synthesis. This is the first study providing preclinical evidence for the protective effect of HSYA against photoaging.
... Immunosuppression has been associated with length of time of exposure, the photoprotective agent used and the species under study 6,9 . In animals, the frequent use of solar photoprotectors has been associated with both a curing of pre-existing damage and the prevention of damage associated to ultraviolet radiation damage 48,49 . ...
The harmful effects of solar radiation on the organism originate mainly from Ultraviolet rays. Sun burn, an acute and visible reaction arising from skin exposure to such radiation, can cause serious coetaneous lesions, cellular des- truction and harmful effects on connective tissue, and may even be accompanied by oedema and loss of liquids. The aims of this work have been to describe and assess the effects of skin reactions to exposure to ultraviolet radiation, to elucidate on different prevention strategies and/or treatment of the sunburn. In general, it seems to be necessary to stress the importance of adopting healthy habits with regard to ultraviolet radiation exposure, especially important in fi rst eighteen y cars of live, and to carry out educational campaigns to prevent the appearance and/or worsening of conditions arising from such.
... Since intracellular ROS was increased modestly with H 2 -lacking RW after UVA-irradiation, it is suggested that 'warm' are not playing a major role in this cytoprotective response (Figs. 4 and 5). Natural evolution of wrinkles starts from a reducible to a permanent skin invagination with differences among individuals depending on age [33], whereas substantial repair is occurred in hairless mice skin after stopping UV-exposure in vivo [34]. In the 3-months clinical study on 6-healthy Japanese volunteers (age: 14-65 years) in HW-bathing of 0.19-0.41 ...
Hydrogen-rich electrolyzed warm water (HW) was prepared at 41°C and exhibited dissolved hydrogen (DH) of 1.13 ppm and an oxidation-reduction potential (ORP) of -741 mV in contrast to below 0.01 ppm and+184 mV for regular warm water (RW). Fibroblasts OUMS-36 and keratinocytes HaCaT were used to examine effects of HW against UVA-ray irradiation. Type-I collagen was synthesized 1.85- to 2.03-fold more abundantly by HW application for 3-5 days than RW in OUMS-36 fibroblasts, and localized preferentially around the nuclei as shown by immunostain. HW application significantly prevented cell death and DNA damages such as nuclear condensation and fragmentation in UVA-irradiated HaCaT keratinocytes as estimated by WST-1 and Hoechst 33342 assays. HW significantly suppressed UVA-induced generation of intracellular superoxide anion radicals in both the cell lines according to NBT assay. Wrinkle repression was clinically assessed using a HW-bathing. Six Japanese subjects were enrolled in a trial of HW-bathing (DH, 0.2-0.4 ppm) every day for 3 months. HW-bathing significantly improved wrinkle in four subjects on the back of neck on 90th day as compared to 0 day. Thus, HW may serve as daily skin care to repress UVA-induced skin damages by ROS-scavenging and promotion of type-I collagen synthesis in dermis.
... DerAutier 1999;Autier 2000 Lage sind, UV-induzierten Sonnenbrand (Pathak 1982, Elmets 1992 ) , chronischrezidivierenden Herpes labialis (Rooney 1991), chronisch aktinische Dermatitis und Erythropoetische Protoporphyrie (Diffey 1991) Hautalterung (Photoaging) (Kligman 1983, Kligman 1985), DNS-Schäden (B8-10), Ausbildung von präkanzerösen Aktinischen Keratosen (Freeman 1988; De Rijcke 1989; van Praag 1993Morison 1984; Morison 1985a; Morison 1985b; Edwards 1986) Arbeiten zeigt sich, dass Sonnenschutzmittel besser vor lokalen immunsuppressiven UV-Effekten (Ho 1992, Wolf 1993 Roberts 1996; Miyagi 1994, Hayág) als vor systemischen Effekten von UV-Licht schützen (Hersey 1987; Gurish 1981,Reeve 1991). Bei einer bestimmten UV-Dosis schützen demnach Lichtschutzfilter besser vor Sonnenerythem als vor immunologischen Veränderungen (Wolf 1993, Walker 1997 Es konnte demonstriert werden, dass UV-induzierte Immunsuppression auch dann erfolgen kann, wenn ein Sonnenerythem infolge eines suffizienten UV- Lichtschutzfilters ausbleibt (Wolf 1993a, Walker 1997, Wolf 1993b). ...
Sonnenschutzfilter dienen der Prophylaxe von akuten und chronischen UV-Schäden. Der LSF trifft eine Aussage über die erythemprotektive Wirkung im Bereich der UV-B-Strahlung, gibt jedoch keine Auskunft über den UV-A-Schutz oder eine eventuell vorhandene oder fehlende immunprotektive Wirkung. Verschiedene Untersuchungen in vitro und in vivo im Tiermodell haben sich mit der Frage der immunprotektiven Eigenschaften von Sonnenschutzfiltern auseinandergesetzt, allerdings gibt es nur wenige Arbeiten, die sich mit den in vivo Bedingungen im humanen Modell auseinandersetzen. Es konnte belegt werden, dass steigende Dosen von UV-B-Strahlung (0-100 J/m²) in transformierten (KB Zellen) oder normalen humanen Keratinozyten (HNK), dosisabhängig die Zytokin-(IFN-g, TNFa)-induzierte ICAM-1-Expression inhibieren. Diese Eigenschaft wurde in dieser Arbeit zu nutze gemacht, um im humanen in vivo Testsystem, den Nachweis zu erbringen, dass Lichtschutzfilter in der Lage sind vor UV-B bedingter Immunsuppression zu schützen. Als biologischer Marker wurde hierfür die UV-B-induzierte Hemmung der zytokinabhängigen ICAM-1 Expression als Read-out-System genutzt. Es konnte nachgewiesen werden, dass eine 2%-ige Uvinul-Formulierung und eine 5%-ige Parsol-Formulierung in der Lage sind, nicht nur vor UV-B-Strahlung im Bereich des ausgewiesenen LSF zu schützen, sondern auch in erheblichem Maße vor UV-B bedingter Suppression der IFN-g-induzierter ICAM-1 Aufregulierung. Hiernach sind diese Lichtschutzfilter also in der Lage nicht nur vor UV-B bedingtem Erythem sondern auch vor UV-B bedingter Immunsuppression zu schützen.
... Exposure started 24 h after fertilization (24 h-PFS) then at intervals, 48, 72, 96, 120, 144 and 168 h PFS. Fertilized eggs were divided into four groups: one control and three groups irradiated once for 15, 30 and 60 min according to Kligman et al. (1983) and Häkkinen and Oikari (2004). Exposure took place in 12 petri dishes (14 cm in diameter and 2.5 cm high) with 3 petri dish replicates for each group. ...
Many ultraviolet-A (UVA)-induced biochemical and physiological changes are valid as biomarkers using aquatic species for detection of the degree of stress. Changes in the concentration and activities of enzymes, such as glucose-6-phosphate dehyderogenase (G6PDH), lactate dehyderogenase (LDH), DNA damage and lipid peroxidation (LPO), can be used as biomarkers to identify possible environmental contamination in fish. This study aimed to investigate the impact of UVA on the activity of the selected enzymes, DNA damage and LPO during early developmental stages of the African catfish Clarias gariepinus. Embryo hemogenates were used for measurements of G6PDH, LDH, DNA damage and LPO concentrations and activities spectrophotometrically at 37 degrees C. The normal ontogenetic variations in enzyme activities, DNA damage and LPO of the early developmental stages (24-168 h-PFS; hours-post fertilization stage) were studied. There was a significant decrease in the activity of G6PDH till 120 h-PFS. Then after 120 h-PFS, the activity of such enzymes insignificantly increased toward higher stages. The LDH activity was recorded with a pattern of decrease till 96 h-PFS, followed by a significant increase toward 168 h-PFS. The polynomial pattern of variations in DNA damage and LPO was also evident. The patterns of the enzyme activities, corresponding DNA damage and LPO of the early ontogenetic stages under the influence of three different UVA doses (15, 30 and 60 min), were recorded. The pattern of variations in G6PDH activity in UVA-induced groups was similar to that of the control group with variation in the magnitude of such activity. In all treated groups, LDH activity decreased till 96 h-PFS, then increased till 168 h-PFS. Within each of the embryonic stages, the increase in UVA led to a significant increase in DNA damage. A significant increase in lipid peroxidation under UVA doses was recorded. The variability in number and molecular weight of proteins under exposure to UVA was evident, reflecting some of the genetic and transcriptional changes during exposure and development.
... Exposure started 24 h after fertilization (24 h-PFS) then at intervals, 48 h, 72 h, 96 h, 120 h, 144 h and 168 h-PFS. Fertilized eggs were divided into four groups: one control and three groups irradiated once for 15 min, 30 min, and 60 min according to [21,22]. Exposure took place in 12 Petridishes (14 cm in diameter and 2.5 cm high), three Petridish replicates for each group. ...
Exposure to ultraviolet radiation has been associated with variety effects in many organisms ranging from molecular and tissue damage to population level effects. The exposure of embryos of the catfish, Clarias gariepinus (Burchell, 1822) to 366nm UVA at different doses 15, 30 and 60 min resulted in the hatching time delayed to 29 h-post-fertilization stage (29 h-PFS) in comparison with normal hatching time of 22h-PFS at 29 degrees C. In embryos exposed to 15 min/UVA, 30 min/UVA and 60 min/UVA the total percentage of hatched embryos/fertilized eggs were 90%, 89% and 85%, respectively, while in control was 95% at 29 h-PFS. The total percentage of mortality/ hatched embryos were (1-14)%, (2-22)%, (2-23)% and (3-40)% for control, 15 min, 30 min and 60 min groups, respectively, at 40 h-PFS. Also as a result some morphological malformations; (yolk sac oedema, body curvature, fin blistering, and dwarfism) were revealed. These destructive effects were also confirmed by histopathological changes in gills, eyes, intestinal tract, spinal cord, notochord, liver, skin and kidney. The results confirm that exposure to UVA caused an exposure time-dependent delay in hatching rate and reduced the percentage of the hatched embryos but the mortality rate increased with increase of the exposure time to UVA.
Background:
Sunscreens are known to protect from sun damage; however, their effects on the reversal of photodamage have been minimally investigated.
Objective:
The aim of the prospective study was to evaluate the efficacy of a facial sun protection factor (SPF) 30 formulation for the improvement of photodamage during a 1-year use.
Methods:
Thirty-two subjects applied a broad spectrum photostable sunscreen (SPF 30) for 52 weeks to the entire face. Assessments were conducted through dermatologist evaluations and subjects' self-assessment at baseline and then at Weeks 12, 24, 36, and 52.
Results:
Clinical evaluations showed that all photoaging parameters improved significantly from baseline as early as Week 12 and the amelioration continued until Week 52. Skin texture, clarity, and mottled and discrete pigmentation were the most improved parameters by the end of the study (40% to 52% improvement from baseline), with 100% of subjects showing improvement in skin clarity and texture.
Conclusion:
The daily use of a facial broad-spectrum photostable sunscreen may visibly reverse the signs of existing photodamage, in addition to preventing additional sun damage.
Cartilage oligomeric matrix protein (COMP) is a structural component of cartilage. Recent studies have described COMP as a pathogenic factor that promotes collagen deposition in fibrotic skin disorders such as scleroderma and keloid skin. Although collagen, a major dermis component, is thought to decrease in photoaged skin, recent reports have demonstrated the presence of tightly packed collagen fibrils with a structural resemblance to fibrosis in the papillary dermis of photoaged skin. Here we examined how photoaging damage relates to COMP expression and localization in photoaged skin. In situ hybridization revealed an increase in COMP-mRNA-positive cells with the progress of photoaging in preauricular skin (sun-exposed skin). The signal intensity of immunostaining for COMP increased with photoaging in not only the papillary dermis but also the reticular dermis affected by advancing solar elastosis. Immunoelectron microscopy detected the colocalization of COMP with both elastotic materials and collagen fibrils in photoaged skin. Ultraviolet light A irradiation of human dermal fibroblasts induced COMP expression at both the mRNA and protein levels. Ultraviolet light A-induced COMP expression was inhibited by an anti-transforming growth factor-β antibody or SB431542, an activin receptor-like kinase 5 inhibitor. These results suggest that the transforming growth factor-β-mediated upregulation of COMP expression may contribute to the modulation of dermal extracellular matrix in the photoaging process.
Ultraviolet (UV) radiation is increasingly recognized as the cause of a vast number of changes in the skin of humans and animals. These include alterations at the molecular, cellular, tissue and systemic levels. In the recent past, much has been learned about the immediate effects in skin of acute UV exposure (i.e. sunburn) with its epidermal cell death, inflammation and vasodilation (1,2). With chronic exposure, many of the clinical and histologic effects can be seen only after decades. Visually, these are hyper-and hypopigmented macules, dry scaly, wrinkled skin with a variety of benign, pre-malignant and malignant neoplasms. All epidermal in origin, they lead, inexorably in humans, to the appearance we described as photo-aged (3). Underlying many of these visible manifestations are drastic changes in the dermis. These relate chiefly to destruction of mature collagen, with a compensatory overproduction of reticulin fibers, hyperplasia of elastic fibers eventuating in elastosis, increased levels of the glycosaminoglycans (GAGs) comprising the ground substance and changes in the microvasculature. First described in actinically damaged humans (4,5), systematic investigation required an animal model.
Exposure to terrestrial solar (sunlight) ultraviolet radiation (UV) is a primary environmental human health hazard. Reports of increased incidence of skin cancer and reduced levels of UV-filtering atmospheric ozone have raised public awareness and concerns about the health risks associated with UV exposure. Public health education programs focused on reducing the risk of solar UV overexposure advocate avoiding mid-day sun exposure, wearing protective clothing and sunglasses, and applying sunscreen to exposed skin.1 Studies have shown that sunscreens prevent UV-induced sunburn (erythema),2 photoaging,3,4 episodes of recurrent herpes labialis (cold sores),5 DNA damage to skin cells,6–8 development of precancerous actinic keratoses,9,10 as well as initiation11,12 and promotion13 of skin cancers. There is confusion, however, regarding the efficacy of sunscreens to prevent UV-induced immunosuppression, due to conflicting results reported in various published studies.14–41
Broad spectrum, high sun protection factor (SPF) sunscreens have been shown, unequivocally, to prevent sunburn as long as the UV dose does not exceed the protective factor of the sunscreen.1, 2 Although the acute effects of sunlight can be readily studied in humans, assessment of sunscreen efficacy against the damage caused by chronic irradiation requires an animal model. The hairless mouse has been and continues to be a useful model for these purposes.3 High SPF products have been shown to prevent UVB-induced carcinogenesis in these mice.4,5 The model has been established as a relevant one for the study of photoaging 3,6,7 because the dermal connective tissue changes closely resemble those found in human sun worshippers.8 Sunscreen prevention of UVB-induced photoaging has been repeatedly demonstrated.6,7,9 Dermal damage induced by long-term UVA exposure has also been prevented by sunscreens containing UVA-absorbing molecules.10, 11 Similarly, sunscreen protection against chronic exposure to solar simulating radiation (UVB plus UVA) has been shown.12 In summary, experimental studies with the hairless mouse have reported that sunscreens provide virtually complete protection against photodamage resulting from chronic exposure to UV radiation.
The increase in UV irradiation on earth due to the stratospheric ozone depletion represents a major environmental threat to the skin increasing its risk of photooxidative damage by reactive oxygen species (ROS). ROS have been implicated in several photodermatological disorders including photoaging. The clinical manifestations of cutaneous photoaging are due to quantitative and qualitative alterations of the dermal connective tissue. Therefore, we were interested to better define the involvement of ROS in the up-regulation of matrix-metalloproteinases (MMP) responsible for connective tissue degradation in photoaging, tumor invasion and metastasis. For this purpose fibroblast monolayer cultures have been subjected to various UV modalities. In parallel fibroblasts have been challenged by distinct ROS generating systems. Using non-toxic concentrations of scavengers, enhancers, and chemicals which specifically inhibit the activities of ROS detoxifying enzymes, stably transfected fibroblast cell lines overexpressing ROS detoxifying enzymes, and iron chelators blocking the Fenton reaction, distinct ROS have been increased perior intracellularly. A time and dose dependent increase in mRNA and protein levels for collagenase was observed after exposure of fibroblasts to UVB, UVA, 1O2, H2O2, O2, or OH generating systems. After UVB irradiation inhibition of the Fenton reaction using iron chelators abrogated the MMP induction substantially. Scavengers for the hydroxyl radical reduced the MMP induction after UVB, thus pointing to the importance of the Fenton reaction and the hydroxyl radical in the UVB response. By modulating the lifetime of 1O2 by enhancers and quenchers, singlet oxygen could be identified as a crucial mediator of the UVA response. In addition, the inhibition of glutathione peroxidase, catalase and the Fenton reaction enhanced MMP mRNA induction whereas inhibition of superoxide dismutase diminished the MMP mRNA increase. Furthermore, exposure to UVA of a stably transfected fibroblast cell line overexpressing the manganese superoxide dismutase resulted in a substantial increase in MMP mRNA. These results indicate that following UVA irradiation, beside 1O2, H2O2 is mainly responsible for the induction of MMP synthesis. In conclusion, we have identified distinct ROS involved in matrix-degrading enzyme induction resulting in tissue degradation following UV irradiation and have outlined preventive strategies which may enhance the rational development of photoprotective agents.
In the cosmetic industry, the fineness of TiO2 powder is a key factor for maximizing its UVB-protecting ability. Although the sol-gel method using tetraisopropyl orthotitanate (TIPOT) is one of the effective ways to make fine particles of TiO2, it is difficult to control the particle size and to make non-aggregated TiO2. Different from an ordinal sol-gel method, our new method successfully gave a complex of TiO2 and SiO2 without aggregation of TiO2. After mixing titania sol with acid-type silica sol, the pH of the mixture was gradually adjusted to be 7, resulting in an ordered interaction of the two components. During the mixing process, acid-type silica sol and titania sol interact electro-statically because they have complementary charges. For forming a TiO2/SiO 2 complex powder, the 'interacted' titania-silica sol prevented the aggregation of TiO2 particles even if the pH of the mixture was 7. The complex showed a higher UVB protecting ability than ultra-fine TiO 2, which is commercially available. Transmission electron microscopy and auger electron spectroscopy confirmed a highly ordered structure of TiO 2 and SiO2.We assume the high dispersion of titania sol in the complex can give its high performance against UVB.
In order effectively to treat the patient who presents for rejuvenation of the aging face, it is necessary to be able to evaluate the face and the various factors that go into producing this dynamic picture at any given time.
The technology of skin care is broad and differs from many other cosmetic categories because of the functional nature of many of the products. There are products that primarily have cosmetic effects and products that have very significant pharmacological effects. All products, however, are designed to interact and treat the largest organ of the body—the skin. To understand the need for the category, one must understand the business. The skin-care business is very large worldwide, with total sales of over 10 billion dollars divided between mass and prestige distribution. Mass is roughly 60% and prestige roughly 40%. The largest markets are Japan, at 3.5 billion dollars, the US at 2.5 billion dollars, and western Europe at 3 billion dollars.
Zusammenfassung
Durch sinnvollen Lichtschutz gegen ultraviolette (UV) Strahlung können akute Hautschäden sowie chronische Hautveränderungen vermieden werden. Unter den verschiedenen Lichtschutzpräparaten wird besonders durch die Anwendung von Sonnencremes mit höherem Lichtschutzfaktor neben der Unterdrückung eines UV‐induzierten Erythems auch die UV‐induzierte Immunsuppression verhindert. Dieser Schutz wird teilweise durch die Hemmung der Freisetzung von mehreren immunsuppressiven Mediatoren aus der Epidermis erzielt. Besonders der Schutz vor Immunsuppression dürfte für die reduzierte Entwicklung von UV‐induzierten Hauttumoren nach regelmäßiger Anwendung von Sonnencremes mitverantwortlich sein. Neben Immunsuppression kann UV‐Strahlung auch DNS‐Mutationen induzieren, die häufig in Zellzyklus‐regulierenden Genen nachweisbar sind. Durch die topische Applikation von DNS‐Reparaturenzymen können diese DNS‐Schäden behoben werden und es entwickeln sich daher weniger Hautmalignome. Zukünftige Entwicklungen von effektiveren Lichtschutzpräparaten, die möglicherweise auch DNS‐Reparaturenzyme oder Substanzen enthalten, welche die endogene DNS‐Reparatur induzieren, werden weiterhin die Lichtschutzmöglichkeiten verbessern. Bis diese Entwicklungen in die Realität umgesetzt werden, bleibt ein der unterschiedlichen Komplexion entsprechender Lichtschutz vorrangiges Ziel.
Zusammenfassung
Die Belastung der Haut mit natürlicher und künstlicher UV‐Strahlung hat in den letzten Jahren nicht nur durch die verstärkte solare Strahlung als Folge der Ozonabnahme in der Stratosphäre, sondern auch durch ein Freizeitverhalten mit dem Wunsch nach gebräunter Haut deutlich zugenommen. Dieser Wunsch wird nicht nur durch Reisen in die sonnigen Gebiete der Erde, sondern auch durch den häufigen Besuch von Solarien umgesetzt. Hinzu kommt die gestiegene Lebenserwartung in den Industrienationen, die mit einer gesteigerten kumulativen UV‐Belastung korreliert. Konsequenz daraus ist zusätzlich zu Immunsuppression und Hautkarzinogenese auch die Photo‐ oder Lichtalterung der Haut durch den photooxidativen Schaden an Zellen, subzellulären Kompartimenten und Makromolekülen, der durch die Absorption von Photonen in einer sauerstoffreichen Umgebung entsteht. Klinisch manifestiert sich die Photoalterung der Haut in Faltenbildung, Gewebeschlaffheit, ledrigem Erscheinungsbild mit Fragilität, Verletzbarkeit und eingeschränkter Wundheilung. Strategien zur Vermeidung oder Minimierung dieser photooxidativen Langzeitschäden umfassen effektiven UV‐Schutz und das Aufrechterhalten eines oxidativ‐antioxidativen Gleichgewichtes in Zellen und Geweben. Neuere Therapieentwicklungen wie der Einsatz von DNA‐Reparaturenzymen werden ebenfalls diskutiert.
Fine particles of titanium dioxide (TiO2) are effective UV-protecting inorganic materials in cosmetic products. The particles have the tendency to make flocs in liquids and the ability of UV light scattering of the suspensions strongly depends on the size of flocs. The degree of flocculation should be related to the rheological properties, and UVprotecting ability of the suspensions was investigated as a function of the size of flocs formed in a dispersion procedure during sample preparation. Essential requirements for UV-protecting cosmetics are strong cut-off ability for the UV light and high transparence for the visible light. Excellent balance of these optical properties was achieved in the suspensions of TiO2 particles with floc diameters ranging from 100 to 120 nm. When the floc diameter was decreased less than 100 nm in the dispersion procedure, the suspensions turned to shear-thinning fluids from Newtonian ones. Such the change in rheological behavior can be used to obtain TiO2 suspensions possessing the designed UV-protecting ability and flow behavior.
The harmful effects of solar radiation on the organism originate mainly from Ultraviolet rays. Sun burn, an acute and visible reaction arising from skin exposure to such radiation, can cause serious coetaneous lesions, cellular destruction and harmful effects on connective tissue, and may even be accompanied by oedema and loss of liquids. The aims of this work have been to describe and assess the effects of skin reactions to exposure to ultraviolet radiation, to elucidate on different prevention strategies and/or treatment of the sunburn. In general, it seems to be necessary to stress the importance of adopting healthy habits with regard to ultraviolet radiation exposure, especially important in first eighteen y cars of live, and to carry out educational campaigns to prevent the appearance and/or worsening of conditions arising from such.
Exposure of humans to solar radiation seems to be the major carcinogenic agent in the etiology of human skin cancers, at least for basal and squamous cell carcinoma [1, 2]. The biological effects of ultraviolet (UV) components of sunlight that could be involved in this tumoral development include DNA damage and epidermal hyperplasia (for review see [3]). moreover, there is increasing evidence that UV-induced immunomodulatory effects may be important in the development of skin cancer in humans [4]. This immunosuppression can be detected by impaired generation of contact hypersensitivity (CHS) reactions to haptens in both humans [4] and laboratory rodents [5] and decreased reactivity against highly antigenic tumors in mice [6].
A screening method for determining sun protection factor (SPF) values of prototype sunscreen formulations has been developed using guinea pigs. Two sets of experiments were done to substantiate the guinea pig as a reliable model for SPF determinations. In the first set of experiments, SPFs of two commercially available sunscreens and a homosalate control were determined in guinea pigs and human subjects, using artificial light. Statistical analysis of data for the two commercial products confirmed that the guinea pig model could successfully predict the SPF values established by human testing. The average SPF value obtained in guinea pigs using 8% homosalate was significantly different when compared to the human test. A second set of experiments compared the claimed SPF on the packages of four commercially available sunscreens with SPF values determined in the guinea pig test. The average SPF values experimentally derived in the guinea pig were not statistically different from the claimed values. The results of these studies demonstrate that the guinea pig is a reliable model to screen for SPF values of prototype sunscreen products. This guinea pig method is not meant to be a substitute for human data, which are necessary to substantiate a claimed SPF on a commercial package. The method in the FDA Proposed Sunscreen Monograph (human testing) must still be used for that purpose.
Titanium dioxide (TiO2) and zinc oxide (ZnO) particles are very effective as UV-protecting inorganic materials in cosmetic products, but they tend to form flocs in a liquid. Because the UV scattering of suspensions strongly depends on the floc size, the degree of flocculation can be evaluated by rheological technique. To control the flocculation level of complex suspensions, polyoxyethylene (POE)-modified silicones of ABA-type in which the POE groups are incorporated between terminal groups of dimethylpolysiloxane (DMPS) are used as dispersants. Based on the experimental results that the suspensions consisting of small flocs show low viscosity and high UV-protection, it is confirmed that the optimum HLB value which contributes to excellent UV scattering is lower for dispersants with higher molecular weight. In adsorption, the POE groups attach to the particle surfaces and the silicone groups are in an extended conformation. The steric stabilization mechanism is responsible for low viscosity of suspensions. Since the conformation of adsorbed chains is determined by the adsorption energy of POE and loss of conformational entropy of DMPS, the molecular weight of PEO and balance between PEO and DMPS play a crucial role in controlling the flocculation level and UV-protecting ability.
Expense and inconvenience have restricted the use of the filtered xenon are lamp (solar simulator) as a UV source for conducting large-scale animal studies. Because sunscreen immunoprotective levels are significantly affected by the UV power spectrum of the source it is imperative that a solar simulating source be used for accurate measurements of sunscreen protection levels that are relevant to human UV exposures from sunlight. However, relatively inexpensive sunlamps, e. g. the UVA-340, that emit a UV power spectrum similar to that of a solar simulator are available. Unlike FS-type UVB sunlamps, which have a significant amount of effective immunosuppressive nonsolar UV energy at wavelengths below 295 nm, the immunosuppression effectiveness spectrum of UVA-340 sunlamps was nearly identical to that of a solar simulator. The purpose of this study was to evaluate this sunlamp for conducting photoimmunological and sunscreen immune protection studies. Groups of C3H mice were exposed to a range of UVA-340 sunlamp doses (0.25 KJ/m2 to 20.0 KJ/m2) to establish a dose-response curve and determine the minimum immune suppression dose (MISD) for induction of local-type suppression of contact hypersensitivity (CH). The MISD, defined as the lowest UV dose given to produce ∼50% suppression of the CH response in mice, was determined to be 1.0 kJ/m2 for UVA-340 sunlamps. Immune protection tests on four marketed sunscreen lotions (sun protection factors [SPF] 4, 8, 15 and 30) were then conducted with UVA-340 sunlamps using MISD as the endpoint. The immune protection factors for these sunscreens were equivalent to the level of protection predicated by their labeled SPF. These results are similar to those we have previously obtained using a solar simulator. We conclude from these data that the immunosuppressive effects of UVA-340 sunlamps are similar to those of a solar simulator; however, further studies are needed to determine if UVA-340, or similar, sunlamps are a viable alternative to the solar simulator for conducting large-scale animal experiments that require a relevant UV solar spectrum.
Chronic ultraviolet B (UVB) exposure of human or murine skin is known to induce cutaneous photoaging and enhanced carcinogenic risk. An extract of Polypodium leucotomos (PL), a tropical fern plant, has been known to exhibit interesting antioxidant and photoprotective properties against acute exposure to ultraviolet radiation. The objective of this preliminary (or pilot) study was to determine the photoprotective role of topically applied Polypodium leucotomos extract in the prevention or amelioration of cutaneous changes of photoaging in hairless mice. PL-treated mice showed significant reduction of skinfold thickness than those observed in PL-untreated controls. Additionally, PL-treated mice showed a significantly lower degree of histologic parameters of photoaging damage, including dermal elastosis, compared with positive control mice. Interestingly, PL treatment also showed reduction in the number of mice showing skin tumors at 8 weeks after the cessation of the UVB exposure protocol. The results of this preliminary study illustrate that PL treatment helped to ameliorate and to partially inhibit some of the histologic damage associated with photoaging of skin and appeared to contribute to a decrease in the prevalence of UVB-induced skin tumors in mice.
The use of sunscreen products has been advocated by many health care practitioners as a means to reduce skin damage produced by ultraviolet radiation (UVR) from sunlight. There is a need to better understand the efficacy and safety of sunscreen products given this ongoing campaign encouraging their use. The approach used to establish sunscreen efficacy, sun protection factor (SPF), is a useful assessment of primarily UVB (290–320 nm) filters. The SPF test, however, does not adequately assess the complete photoprotective profile of sunscreens specifically against long wavelength UVAI (340–400 nm). Moreover, to date, there is no singular, agreed upon method for evaluating UVA efficacy despite the immediate and seemingly urgent consumer need to develop sunscreen products that provide broad-spectrum UVB and UVA photoprotection. With regard to the safety of UVB and UVA filters, the current list of commonly used organic and inorganic sunscreens has favorable toxico-logical profiles based on acute, subchronic and chronic animal or human studies. Further, in most studies, sunscreens have been shown to prevent the damaging effects of UVR exposure. Thus, based on this review of currently available data, it is concluded that sunscreen ingredients or products do not pose a human health concern. Further, the regular use of appropriate broad-spectrum sunscreen products could have a significant and favorable impact on public health as part of an overall strategy to reduce UVR exposure.
Abstract— The mouse Skh:HR-2 has been reported to be sensitized to ultraviolet light and become pigmented. Using three independent parameters associated with pigmentation. we have examined the ability of the mouse to become pigmented. The methods utilized were spectroscopic (skin color). histological (melanocyte density and epidermal thickness), and biochemical (tyrosinase activity). Following a two-week ultraviolet exposure, the mice were pigmented with the degree of pigment change related to the ultraviolet dose administered. Perturbations in skin color, epidermal thickness, melanocyte density, and tyrosinase activity were recorded. Mice were also examincd for their response to tyrosinc applied topically following each ultraviolet exposure. With the exccption of epidermal thickness. all the pigmentation parameters were accentuated when compared to results from ultraviolet exposure alone.
Chronological (intrinsic) aging is that associated with the passage of time and a consequent decline in biological functions.
This form of aging has a signature in the skin, evident clinically as fine wrinkling and/or skin laxity. Photoaging occurs
concurrently with chronological aging but only on sun-exposed sites, and is induced by repeated exposure to ultraviolet (UV)
radiation. Chronically, sun-exposed skin has distinctive changes including coarse wrinkles, dyspigmentation, telangiectasias,
and a propensity to develop precancerous lesions and subsequent skin cancer. Anecdotally, people of skin of color tend to
“age better” than their white counterparts. At the same age, people with black skin are thought to have fewer wrinkles compared
to those with lighter skin.1 Differences in the structure and physiology of skin of color may account for observed differences in incidence and presentation
of photoaging in people of color. In darker skin, the melanosomes are larger, more oval, and nonaggregated and along with
a higher total melanin content, may confer an increased natural photoprotection from UV radiation.2
Most of the effects of the sun, particularly ultraviolet rays (UV), on the skin are harmful. Recent studies have clearly shown that UVA could be just as damaging as UVB via an indirect mechanism involving generation of oxygen-derived free radicals (OFR). Artificial photoprotection is designed to complete and palliate the deficiencies of natural photoprotection, either by passively preventing penetration of radiation to vital cell targets (clothing, sunscreens) or by blocking overproduction OFRs or by reinforcing or inducing an endogenous photoprotective mechanism. Artificial photoprotection has been largely based on sunscreens. Although these products are very effective against sunburn, their protection against the other effects of the sun is less apparent and must be clearly established. Moreover, they are not completely harmless, as they may induce cutaneous intolerance with long-term use. They are also expensive and fairly fastidious to apply for everyday use, which partly explains their poor use, which can limit their efficacy. Oral administration of free radical scavengers constitutes an attractive alternative. Unfortunately, the hopes raised by in vitro and animal studies have not yet been confirmed in man, due to the incomplete knowledge of anti-free radical defence and kinetic adapted to the redox potential of the cell. New studies should open up new horizons. The best photoprotection at the present time therefore remains avoidance of the sun and photoprotective clothing.
Protection from solar ultraviolet radiation is discussed. Methods of protection include avoiding outdoor activities during times of greatest ultraviolet radiation insolation, seeking shade while outdoors, and wearing appropriate clothing. Sunscreens are reviewed, including newer compounds that may also offer photoprotection.
Caryodendron orinocense, Karst., is a tree that grows along the eastern base of the Andes mountains in Venezuela, Ecuador, and Colombia. It is known in Venezuela as 'Nuez de Barinas, nuez or nogal de Barquisimeto' and in other countries as 'inchi', 'taque', 'abay' or 'palo de nuez'. The oil extracted from the 'nuts' (seeds) is edible. The objective of this study was to assess the potential use of the oil extracted from the seeds in cosmetics. The organoleptic characteristics, some physical (viscosity, specific density, extensibility, UV absorbance), and chemical (fatty acid profile, titratable acidity, saponification index, unsaponifiable matter and peroxide value) characteristics, were determined by official methods. The results show a high polyunsaturated fatty acid content (75.13%) and good physical, chemical and toxicological characteristics appropriate for use in cosmetics. It was concluded that the Caryodendron oil should be useful in cosmetic formulations.
Topically applied retinoic acids have been found to enhance the gene expression for collagen types I and III in the skin of UVB-irradiated hairless mice. Prior damage is required because the effect is not observed in the skin of age-matched, non-irradiated control animals. Immunochemical methods have shown an increase in TGF-beta 1 and, to a lesser extent, of TGF-beta 2 in the epidermis following retinoic acid treatment. There were no changes in mRNA levels for any of the isotypes of TGF-beta induced by retinoic acid treatment. This study suggests that TGF-beta may mediate the effect of retinoic acids on dermal repair through the stimulation of collagen gene expression.
The mechanisms of UV-induced ageing and carcinogenesis of the skin have been elucidated in animals and humans, and both UVB and UVA radiation have been shown to have deleterious effects on the skin. Thus the use of solaria which deliver mostly UVA radiation is not safe. There is also an increased risk of ageing when using therapeutic UV sources. UV radiation is beneficial in many cases of skin disorders such as psoriasis, atopic eczema, acne and pruritus. Nevertheless by careful patient selection and follow-up the risks of UV can be minimised when treating patients with artificial UV radiation. During recent years there has been intensive research into the development of agents which prevent harmful effects of radiation. The retinoids are particularly interesting as they enhance skin repair after UV damage, have an anticarcinogenic effect and are effective for treating precancerous lesions such as solar keratosis and as adjuvant therapy for skin cancers. Topical retinoids are already used for the treatment of actinic skin damage, and systemic retinoids are also used in certain groups of patients who have an increased risk of contracting skin cancers such as xeroderma pigmentosum.
‘Ageing is a multistep, multifaceted, time-dependent phenomenon characterized by the decreased ability of a system to respond to exogenous and endogenous stress from either physical, chemical or biologic agents’.1 Cutaneous ageing provides a visible model of the interaction between endogenous (intrinsic) factors and exogenous (extrinsic) factors. In skin, the principal extrinsic-factor is ultraviolet light (UV) which is responsible for the constellation of changes termed photoageing. In recent years, much interest has been directed towards defining the ageing processes in skin and excellent comprehensive reviews have been compiled.2,3 This review aims to highlight several areas of developing knowledge, and focuses on the potential importance of environmental changes as they influence skin ageing and carcinogenesis.
Repeated reference to the effects of UV on the skin are inevitable in any review of skin ageing and this is scarcely surprising as the skin contains many cells as well as subcellular and extracellular chromophores which are capable of absorbing energy within the UV spectrum.4 Cellular chromophores include among others keratinocytes, melanocytes, Langerhans cells, dermal fibroblasts and mast cells. Subcellular chromophores include keratin, melanin, collagen, elastin and a number of proteins, lipids and steroids (such as vitamin D). Urocanic acid, a photoisomerization product of the amino-acid histidine, may provide some limited photoprotection and some believe it to be important in UV induced immunosuppression.5
Understanding events at the molecular and biochemical level has unfortunately not been paralleled by clinical advances and the common, troublesome skin-problems of old age such as cancer, xerosis and pruritus remain a major cause of morbidity and yet are poorly explained.
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.
The infrastructure of hairless mouse skin exposed to UVB radiation and followed by retinoic acid treatment was studied to identify alterations induced in both epidermis and dermis. Female mice were irradiated 3 times weekly for 5–6 months; a group of these mice was then treated topically 3 times weekly for 10 weeks with either 25 μg all‐trans‐retinoic acid dissolved in acetone or with acetone alone. Age‐matched, unexposed, untreated mice served as controls. Cutaneous changes induced by UVB radiation included keratinocyte mitochondrial inclusions often accompanied by damaged cristae, duplication of basement membrane, increased number of dermal fibroblasts, inflammatory cells and elastic fibers, and abnormal elastic fibers. Subsequent retinoic acid treatment resulted in more prominent mitochondrial inclusions which sometimes coalesced to form irregular contoured bodies. Also observed were lipid droplets in the stratum corneum, glycogen deposits in keratinocytes and granular material in dilated keratinocyte endoplasmic reticulum. Poorly differentiated epidermis with necrotic or apoptotic cells was present in some specimens. Elastic fibers were fewer and usually morphologically normal. Skin exposed to UVB and treated with vehicle appeared similar to control except for the presence of excess basement membrane and occasional small mitochondrial inclusions. Because of the heightened concern regarding UV radiation‐induced damage to the human skin and the current topical use of retinoids, the cutaneous changes described are considered worthy of attention.
Feldman D, Bryce GF, Shapiro SS. Ultrastructural effects of UVB radiation and subsequent retinoic acid treatment on the skin of hairless mice.
• The histologic effects of topical tretinoin therapy on photodamaged facial skin were investigated in two 24-week, double-blind, randomized, vehicle-controlled studies involving 533 subjects at eight US centers. Three concentrations of tretinoin (0.05%, 0.01%, and 0.001%) in a new emollient cream were studied. Pretherapy and posttherapy biopsy specimens from the periorbital (crow's foot) area were examined by conventional light microscopy and computerized image analysis. Four significant dose-dependent differences from vehicle were found in the tretinoin groups: increased epidermal thickness, increased granular layer thickness, decreased melanin content, and stratum corneum compaction. There was no significant difference between 0.001% tretinoin and the vehicle, and no obvious dermal changes were detected in any group. The four epidermal changes in tretinointreated skin establish the biologic activity of the new emollient cream formulation and may partially account for the clinical improvements in photodamage observed in the same group of subjects.
(Arch Dermatol. 1991;127:666-672)
The effects of retinoid treatment on wrinkling in the hairless mouse can be understood in the context of the repair of the dermal elastosis. The two isomers of retinoic acid do not differ qualitatively in their effects on the histological appearance of the tissue or on the wrinkling patterns produced. The all-trans isomer is slightly more potent in this system than the 13-cis isomer but substantially more irritating, which may limit the maximum degree of repair attainable. The "reconstructed" dermis is thickened, it contains new collagen as a result of the stimulation of gene expression, and the tangled, disorganized elastin is packed into a thin layer in the lower dermis. Thus, the framework within which a wrinkle had been established is eliminated, and the skin assumes a normal state, as observed. That the effacement is apparently permanent is additional evidence of the relationship between the integrity of the elastic fiber network and the surface appearance. The only difference in the repaired skin is the absence of filamentous surface features. The thickening effect of UVB and subsequent retinoid treatment on the epidermis does not contribute substantially to the overall thickness of the repaired skin. Nevertheless, despite having a minor role in the effacement of deep wrinkles, these epidermal changes evidently preclude the formation of fine surface features. The model is a valid one for the repair of photodamaged skin. From what is known about the role of elastin in maintaining skin integrity and from the association of wrinkling with excessive sun exposure, it is encouraging to observe the dual effect of retinoic acids.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of long-term ultraviolet irradiation on the connective tissue of the skin was investigated in 25 naked (Ng/-) mice which received a total daily radiant dose of 402 J/cm2 for a period of 8.5 months. The produced alterations were very similar to those found in actinic elastosis of humans, as assessed by histologic and electron-microscopic criteria.Der Einflu chronischer UV-Lichteinwirkung auf das dermale Bindegewebe der Nacktmaus (Ng/-) wurde licht- und elektronenmikroskopisch untersucht (25 Tiere; Dauer der Bestrahlung 8,5 Monate; tgliche Strahlendosis 402 J/cm2). Die induzierten Bindegewebsvernderungen entsprechen weitgehend dem Bild, wie es bei der menschlichen aktinischen Elastose angetroffen wird.
The effect of long-term ultraviolet irradiation on the connective tissue of the skin was investigated in 25 naked (Ng/-) mice which received a total daily radiant dose of 40 +/- 2 J/cm2 for a period of 8.5 months. The produced alterations were very similar to those found in actinic elastosis of humans, as assessed by histologic and electron-microscopic criteria.
Application of 5% para-aminobenzoic acid (PABA) to hairless mice one hour Prior to ultra-violet light (UVL) irradiation will almost totally protect these animals from developing tumors induced by chronic exposure to UVL in the 290 to 320 nm range in conjunction with a chemical carcinogen. Mice exposed to UVL and not protected by PABA developed primarily squamous cell carcinomas. Two months after cessation of chronic UVL exposure, the non-PABA-treated irradiated mouse skin appeared thickened, yellow, and wrinkled while showing elevated DNA synthesis, hyperplasia. hypergranulosis, and increased amounts of elastotic material. The PABA-treated skin was grossly normal.
AGING IS an interesting subject which is receiving increasing attention in many fields. There is an ever-enlarging body of information which indicates that many of the phenomena which were previously regarded as "natural" processes resulting from old age are actually due to specific disease processes. The changes occurring with arteriosclerosis are prime examples. Factors contributing to aging and premature aging of the skin have not received adequate attention. There is now considerable evidence that sunlight is responsible for most of the visible degenerative changes that occur with the passage of time.
The laxity and folding of the skin resulting from weight loss should not be confused with aging of the skin, although these occur most frequently in elderly, debilitated people. In Simmond's disease and in Werner's and related syndromes, patients may appear to be prematurely aged and the skin is found to be atrophie; but few studies of the skin
The Journal of Investigative Dermatology publishes basic and clinical research in cutaneous biology and skin disease.
To assess the ability of sunscreens to protect connective tissue from actinic damage, hairless mice were irradiated with Westinghouse FS20 sunlamps thrice weekly for 30 weeks. Each exposure, consisting mainly of UV-B and the less energetic UV-A, was approximately 6 human minimal erythema doses under these lights. One group of animals received irradiation only. The other 2 groups were treated, prior to irradiation, with sunscreens of either low or high sun protection factors (SPF 2 and SPF 15, respectively). Skin biopsies were taken at 10-week intervals and were stained with various histochemical stains to reveal changes in the dermis. The unprotected, irradiated animals showed a great increase in the following: reticulin fibers, elastic fibers to the extent of elastosis, neutral and acid mucopolysaccharides and melanin production. The SPF 15 sunscreen completely prevented these changes. The SPF 2 sunscreen was less effective. These effects were substantiated by ultrastructural examination of the tissues by electron microscopy. A surprising histologic finding was the repair capability of the dermis in the post-irradiation period.
The fine structural organization of the epidermis, dermal-epidermal junction, and papillary dermis from unexposed (upper inner arm) and exposed (dorsal forearm) sites of elderly people was compared to the organization of similar regions of young people. Despite an overall thinning of the viable epidermis there was no morphological evidence that the protective function of the epidermis was compromised by age. The differentiation products associated with the keratinization process were not altered in either appearance or amounts in epidermis from unexposed and exposed old skin. Both sites revealed the presence of a well-formed stratum corneum that was the same thickness as that of the young donors. Unexposed and exposed senile skin displayed a relatively flat dermal-epidermal junction devoid of the micro projections of basal cells into the dermis, an indication of a tissue less resistant to shearing forces.Marked elastogenesis, as evidenced by large amounts of 8- to 11-nm (diameter) microfilaments and fibroblasts containing dilated cisternae of rough endoplasmic reticulum filled with flocculent material, was characteristic of the papillary dermis from unexposed and nonactinically damaged exposed old skin. Conversely, in the papillary dermis (Grenz zone) of actinically damaged senile skin the microfilaments were replaced by densely packed collagen fibrils in a colinear arrangement, pre- dominantly parallel to the skin surface. That this dermal architecture was similar to that seen in various scar tissues suggests the Grenz zone is a microscar.
Chronic dermatosis developed in sparsely-haired, lightly pigmented, ventral body skin in 397 of 1 680 beagle dogs by the time the dogs were 5 1/2 years old. Twenty-six of 55 other beagles had developed by 12 years of age. Squamous cells carcinomas developed in the sites of dermatosis in eight of the 397 younger and five of the 26 older beagles. The lesions resembled solar keratosis (solar dermatosis, actinic dermatosis or senile keratosis) in man. They developed under circumstances suggesting that solar radiation is involved in the pathogenesis, as it is in man.
The Journal of Investigative Dermatology publishes basic and clinical research in cutaneous biology and skin disease.
Luna's stain for mast cells has proved to be superior to Weigert's, Verhoeff's, aldehyde-fuchsin, and orcein in visualizing elastic tissue of mice and men.
We studied by light and electron microscopy the elastic fibers in he sun exposed and sun protected skin of normal and psoriatic individuals of different ages in order to separate the changes of actinic damage from those of chronological aging. The sun exposed skin showed 2 types of elastic fiber abnormalities-one related to actinic damage and the other to chronological aging. The sun protected buttock skin showed only the latter. From ages 30 to 70, a minority of the elastic fibers exhibited abnormalities that appeared to represent a process of fiber disintegration. After age 70, the majority of elastic fibers showed these abnormalities. These abnormalities were present without accompanying inflammatory cells. Also, there was morphological evidence of continuing synthesis of elastic fibers during the lifetime of these subjects, except that from ages 50-93, the fibers appeared to be loosely, rather than compactly, assembled. Incubation of dermal slices from buttock skin of young adults with porcine pancreatic elastase and bovine chymotrypsin produced elastic fiber degradation that closely simulated the changes that were observed in aged sun protected skin. We propose that one of the features of cutaneous aging is a slow, spontaneous, progressive degradative process inherent in the elastic fiber that can be enzymatically accelerated from decades to hours by elastase and chymotrypsin.
The Journal of Investigative Dermatology publishes basic and clinical research in cutaneous biology and skin disease.
The importance of mucopolysaccharides as an integral part of connective tissues has been recognized more and more in recent years. The mucopolysaccharides of the dermis of the skin, both normal and pathological, have been no exception to this extensive and fascinating research. Because of the relative ease with which they are performed, histochemical studies far outnumber the biochemical analyses.
The histochemistry of chronically sun-damaged skin
- Sams
Studies in cutaneous aging: I. The elastic fiher network
- Rraverman
Karly destructive effects of sunlight on human skin
- Kligman