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UV-induced reactive oxygen species in photocarcinogenesis and photoaging
Biological Chemistry
Abstract
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 UV-induced reactive oxygen species (ROS). Increased ROS load has been implicated in several pathological states including photoaging and photocarcinogenesis of the skin. Large efforts have been made to better define the involvement of distinct ROS in photocarcinogenesis and photoaging. Both pathological processes share common features; however, they reveal unique molecular characteristics which finally determine the fate of the cell and its host. As well as causing permanent genetic changes involving protooncogenes and tumor suppressor genes, ROS activate cytoplasmic signal transduction pathways that are related to growth differentiation, senescence, transformation and tissue degradation. This review focuses on the role of UV-induced ROS in the photodamage of the skin resulting in biochemical and clinical characteristics of photocarcinogenesis and photoaging. A decrease in the ROS load by efficient sunscreens and/or otherwise protective agents may represent a promising strategy to prevent or at least minimize ROS induced cutaneous pathological states.
... Besides mitochondria-derived ROS from keratinocytes and fibroblasts, excessive ROS production from environmental pollutants such as UV irradiation, visible light, and ozone can cause extrinsic aging [55,56]. UV irradiation is the most common environmental stress to which the skin can be exposed and can lead to skin aging, also known as photoaging, through the overproduction of ROS [57,58]. Excessive production of ROS in the skin due to various internal or external factors leads to a decrease in the number of keratinocytes and fibroblasts, resulting in decreased epidermal turnover and collagen and proteoglycan deposition [54]. ...
... Considering that the skin is the outermost part of the body, UV irradiation is one of the most common and harmful environmental stressors [56]. UV irradiation of the skin can cause skin aging, known as photoaging, through ROS overproduction [57,58]. Therefore, PDEVs with antioxidant effects have been studied to combat the increased oxidative stress caused by UV radiation. ...
Extracellular vesicles (EVs) composed of a lipid bilayer are released from various cell types, including animals, plants, and microorganisms, and serve as important mediators of cell-to-cell communication. EVs can perform a variety of biological functions through the delivery of bioactive molecules, such as nucleic acids, lipids, and proteins, and can also be utilized as carriers for drug delivery. However, the low productivity and high cost of mammalian-derived EVs (MDEVs) are major barriers to their practical clinical application where large-scale production is essential. Recently, there has been growing interest in plant-derived EVs (PDEVs) that can produce large amounts of electricity at a low cost. In particular, PDEVs contain plant-derived bioactive molecules such as antioxidants, which are used as therapeutic agents to treat various diseases. In this review, we discuss the composition and characteristics of PDEVs and the appropriate methods for their isolation. We also discuss the potential use of PDEVs containing various plant-derived antioxidants as replacements for conventional antioxidants.
... Carbon is found because carbon-containing atmospheric components inevitably adhere to these surfaces. However, the adsorption of carbon on the surface reduces biological activity; therefore, carbon must be reduced to improve activity [43][44][45]. The material's surface acquires active oxygen due to treatment with argon plasma. ...
In this study, we applied argon plasma treatment to titanium surfaces with nanostructures deposited by concentrated alkali treatment and investigated the effects on the surface of the material and the tissue surrounding an implant site. The results showed that the treatment with argon plasma removed carbon contaminants and increased the surface energy of the material while the nanoscale network structure deposited on the titanium surface remained in place. Reactive oxygen species reduced the oxidative stress of bone marrow cells on the treated titanium surface, creating a favorable environment for cell proliferation. Good results were observed in vitro evaluations using rat bone marrow cells. The group treated with argon plasma exhibited the highest apatite formation in experiments using simulated body fluids. The results of in vivo evaluation using rat femurs revealed that the treatment improved the amount of new bone formation around an implant. Thus, the results demonstrate that argon plasma treatment enhances the ability of nanostructured titanium surfaces to induce hard tissue differentiation and supports new bone formation around an implant site.
... 9-HODE has been found in both the epidermal and dermal layers of the skin [14], with higher levels detected in psoriatic skin [15]. Given that UV radiation induces ROS production [16], the relationship between 9-HODE and photoaging is presumed, albeit with limited supporting evidence. ...
Human skin is regularly exposed to ultraviolet (UV) rays from sunlight, leading to photoaging, which differs from intrinsic aging. Although the acute effects of UV exposure have been extensively studied, limited research has addressed the long-term consequences of chronic UV exposure. This study aimed to investigate the underlying causes of chronic photoaging. A questionnaire-based assessment of sunlight exposure was conducted among volunteers in their 20s and 50s, and the stratum corneum of their skin was analyzed for bioactive lipid content. Volunteers were categorized into low and high UV exposure groups based on the questionnaire scores. The analysis results revealed a significant increase in 9-hydroxyoctadecadienoic acid (9-HODE) levels in the skin of individuals in their 50s with high UV exposure. However, UV exposure did not affect 9-HODE levels in the skin of individuals in their 20s. In vitro experiments further indicated that 9-HODE contributes to chronic inflammation, pigmentary changes, and extracellular matrix alterations during photoaging. Specifically, 9-HODE stimulated cytokine production [interleukin-6 (IL6), IL8, and granulocyte-macrophage colony-stimulating factor (GM-CSF)] and reduced dickkopf-1 (DKK1) production in keratinocytes. In fibroblasts, 9-HODE stimulated matrix metalloproteinase-1 (MMP1) and MMP3 production while reducing collagen I (COL1) production. The expression of G2A, the receptor for 9-HODE, was also confirmed in fibroblasts, suggesting that 9-HODE exerts its effects via G2A, as observed in keratinocytes. Overall, these findings indicate that 9-HODE is a mediator of chronic photoaging and highlight its potential significance in photoaging prevention.
... Skin aging is a natural phenomenon that occurs with age and is accelerated by external factors such as exposure to UV radiation. ROS generated by UV radiation activate the MAPK pathway to upregulate MMP synthesis (Scharffetter-Kochanek et al., 1997;Son et al., 2013). Antioxidants such as phenolics can prevent skin aging by scavenging ROS. ...
Canola meal, a by-product of canola oil processing, is a source of bioactive compounds that show antioxidant and skin anti-aging effects through upcycling (i.e., creative reuse). Here we describe the antioxidant and skin anti-aging effects of canola meal extract (CME) obtained by upcycling canola meal. The antioxidant capacity of CME is due in part to its antioxidative phenolics. Seven phenolics, including sinapine and sinapic acid, in CME were identified using ultra-high-performance liquid chromatography–Orbitrap mass spectrometry. Addition of CME (1000 μg/mL) to human dermal fibroblast neonatal cells significantly (p < 0.05) reduced matrix metalloproteinase-12 production and increased pro-collagen Ι alpha 1 content in response to ultraviolet B-induced oxidative stress compared with cells without CME. These results suggest that CME can serve as a functional food ingredient with antioxidant capacity and anti-aging effects on the skin.
Skin ageing results from both the passage of time and from extrinsic forces, predominantly solar ultraviolet irradiation. Intrinsic ageing is characterized by fine wrinkling and homogenous colour on sun‐protected sites whereas extrinsic ageing is characterized by fine and coarse wrinkling, erythema and dyspigmentation on sun‐exposed sites. Two distinct phenotypes of extrinsic ageing have emerged: atrophic and hypertrophic variants. Tools to measure and quantify skin ageing have been developed and offer therapeutic and research applications. Molecular mechanisms distinguishing intrinsic and extrinsic skin ageing are discussed. The implications of skin ageing are cosmetic, medical and social in nature.
The purpose of this study was to illuminate the mechanism by which Schizonepeta tenuifolia Briq. (ST) ethanolic extract prevents skin photoaging in HR-1 hairless mice (HR-1). The ST ethanolic extract alleviated wrinkle formation, epidermal skin thickness, and collagen degradation in skin tissues of ultraviolet B (UVB)-irradiated HR-1 mice. Expression of matrix metalloproteinases (a wrinkle-related marker) was reduced, and tissue inhibitor of metalloproteinase 1 expression was upregulated following application of ST ethanolic extract. Furthermore, skin dehydration and levels of hyaluronidase-1 and -2 (enzymes that break hyaluronic acid) were decreased. Moreover, protein expression of hyaluronan synthases (markers of skin hydration) and hyaluronic acid levels increased following ST ethanolic extract treatment in UVB-induced photoaging HR-1 mice. In addition, the phosphorylation of mitogen-activated protein kinases (MAPKs), including p38, extracellular signal-regulated kinase, and Jun N-terminal kinase was suppressed, and expression of nuclear factor-kappa was reduced. Treatment with ST ethanolic extract also reduced advanced glycation end product (AGE) accumulation and expression of the receptor for AGE (RAGE) in skin tissue. These results suggest that ST ethanolic extract moderates skin damage caused by UVB irradiation via regulating the expression of wrinkle- and hydration-related proteins, MAPKs, and RAGE.
UVB-induced photoaging is characterized by wrinkle formation, slackness, and senile plaques, affecting the health and beauty of human being. Our previous study revealed that exosomes derived from adipose-derived stem cells (ADSCs) could efficiently alleviate UVB-induced photodamage. However, the functional ingredients in exosomes were undefined. LncRNA H19, one of the well-researched lncRNAs in exosomes, exhibits multiple physiological effects. This study aims to demonstrate the photo-protective role of lncRNA H19 on skin photoaging in UVB-irradiated human skin fibroblasts cells (HSFs) and Kunming mice. LncRNA H19-overexpressing exosomes (H19-Exo) were isolated from the supernatant of ADSCs infected with lncRNA H19-loaded lentivirus. The results showed that H19-Exo significantly inhibited MMPs production, DNA damage, and ROS generation, while enhancing procollagen type I synthesis in UVB-irradiated HSFs. Meanwhile, H19-Exo markedly reversed epidermal thickening and collagen degradation in UVB-irradiated mice. Furthermore, luciferase reporter assays indicated that lncRNA H19 acted as a sponge for miR-138 expression, and SIRT1 was targeted by miR-138. Evidences from both in vitro and in vivo studies also revealed that H19-Exo could enhance SIRT1 expression by knocking-down miR-138. In conclusion, lncRNA H19 served as a therapeutic candidate in treating UVB-induced skin photoaging by up-regulation of SIRT1 via miR-138.
This chapter discusses the involvement of free radicals in acute central nervous system (CNS) injury and their relationship to specific pathophysiological events. A great deal of this information has been obtained from investigations demonstrating the protective efficacy of lipid antioxidant agents in the experimental models of acute spinal cord or head injury. Central nervous tissue appears to provide an especially avid environment for the occurrence of oxygen-radical generation and lipid-peroxidative reactions because of a high content of polyunsaturated fatty acids. Free radical-induced microvascular damage triggers a progressive loss of spinal or cerebral vascular autoregulation and post-traumatic hypoperfusion. If this hypoperfusion phenomenon is sufficiently severe, it can lead to secondary hypoxic degeneration of the brain or spinal cord tissue. However, there is also experimental evidence that shows that nervous tissue is directly affected by oxygen radicals and lipid-peroxidative reactions.
Highly reactive oxidative intermediates (ROIs) are released from inflammatory leukocytes, both in vitro and during acute and chronic inflammation in vivo. Although proteolytic damage is considered the principal means by which inflammatory cells damage connective tissues during diseases like rheumatoid arthritis, glomerulonephritis, and adult respiratory distress syndrome, a substantial body of recent evidence suggests that oxidants released by these cells may also be partly involved in host-tissue injury. This chapter summarizes the evidence that these leukocytic products are capable of compromising, directly or indirectly, the biochemical and biophysical properties of host connective tissues. It examines a range of pathological changes and raises some questions regarding future research issues, which focus on the damage caused by oxidative reactions to either the cellular or extracellular matrix components of a particular connective tissue—namely, articular cartilage. Before considering how ROIs may compromise connective tissue structure and function during inflammation, the chapter briefly describes the fundamental structure of connective tissues. To illustrate the major considerations regarding the structure of connective tissues, the chapter presents the example of articular cartilage.
Two in vitro methods to investigate free radical damage to cultured human skin fibroblasts have been used: irradiation with UVA or UVB, producing intracellular free radicals and DNA damage, or free radical production by the enzymatic system hypoxanthine-xanthine oxidase, releasing free radicals into the culture medium. These methods differ not only in the location of the free radicals generated but also in their nature and kinetics. The antioxidant properties of two human plasma extracts A and B (derived from Cohn's fraction IV and Cohn's fraction I + III) were investigated before, during and/or after the oxidative stress. Protection was observed when the fractions were added concomitantly with the enzymatic system (at 5 g/litre, fractions A and B exhibited, respectively, 77 and 50% activity) or during UVB irradiation (37 and 68% activity for fractions A and B, respectively at 5 g/litre). A small degree of protection was observed against UVA damage. No preventive or restorative effect was observed with the UVB system. The two fractions prevented UVA damage (at 2.5 g/litre, fraction A and B elicited 22 and 23% activity, respectively) but only fraction A also exhibited a restorative effect (at 5 g/litre, activity was 26%). One of the protective mechanisms could be the enhancement of intracellular antioxidant enzyme activity by incubation of cells with fractions A and B (after 24 hr of contact with fraction B, total glutathione peroxidase and glutathione peroxidase Se-dependent activities were significantly increased by 60 and 42%, respectively, compared with control values).
Six patients presented with increased fragility of the skin and formation of blisters in response to minimal trauma. All were unable to obtain more than a minimal tan in natural sunlight because of their tendency to burn and had used ultraviolet A sunbeds for prolonged periods.
We followed the course of 56 patients receiving psoralen plus long-wave ultraviolet light (PUVA) therapy. Nonhemorrhagic blisters developed on clinically normal skin on the limbs of seven patients. Seeming to be related to friction and trauma, the blisters form as a result of damage to the basal and suprabasal layers. Perilesional skin specimens from all blistered patients contained granular deposits of C3 at the dermoepidermal junction, around the upper dermal blood vessels, or at both sites. The average time for initiation and complete formation of suction blisters was measured in 51 patients at different stages during the course of PUVA treatment. Blister separation was in the lamina lucida, with the pemphigoid antigen in the roof while the blister floor contained the lamina densa, laminin, and type IV collagen. This impaired dermoepidermal adhesion was a general phenomenon that occurred in all PUVA-treated patients. The mechanism remains to be determined.
Exposure of normal human fibroblasts to visible light (420-490 nm) in the presence of exogenously added 1-100 micrograms/ml bilirubin enhanced the level of DNA strand breakage compared with cells irradiated in the absence of added bilirubin. Treatment of cells in the dark with an irradiated bilirubin solution also induced DNA strand breaks. However, strand breakage was not detected in cells treated with an irradiated bilirubin solution that had been incubated with catalase (H2O2: H2O2 oxidoreductase EC 1.11.1.6). Examination of irradiated bilirubin solutions demonstrated the presence of hydrogen peroxide although, apparently, not at concentrations sufficient to account for the level of DNA strand breakage detected. Hence, irradiation of bilirubin results in the generation of hydrogen peroxide and possibly other peroxides that can cause DNA damage.
A report is made on seven psoriatic cases in whom an acrobullous photodermatosis developed during photochemotherapy. Histologically there were subepidermal blisters without pronounced infectious infiltrate. Provocation of a latent bullous pemphigoides could be excluded by immunofluorescent examinations. Etiologically, a phototoxic degeneration of the stratum malphigi, cell increases in the stratum basale, and connective tissue changes were observed.
The protective activities of hamamelitannin (2',5-di-O-galloyl-hamamelose) in Hamamelis virginiana L. and its related compound, gallic acid, on damaged murine skin fibroblasts induced by UVB irradiation were investigated. In order to exclude the UV absorbing effect of the compounds, the protection study was performed such that the fibroblasts were pretreated with hamamelitannin or gallic acid for 24 h before UVB irradiation. At 200 microM concentration, hamamelitannin gave the higher survival of 72.6 +/- 0.4% in comparison with that of gallic acid (35.5 +/- 1.0%), while UVB absorbers such as 2-ethylhexyl p-methoxycinnamate and hexylbenzoate did not show such protection. The scavenging activities of hamamelitannin and gallic acid against active oxygens such as superoxide anion radicals, hydroxyl radicals and singlet oxygens were evaluated using electron spin resonance (ESR-spin trapping method). Hamamelitannin and gallic acid showed potent scavenging activities against all active oxygens tested. Furthermore, the association of hamamelitannin to fibroblasts was examined by comparing it with that of gallic acid, and the following results were obtained: (1) hamamelitannin reduces the reaction rate of liposome entrapped-nitroblue tetrazolium (NBT) with external superoxide anions, and (2) several glycosides associate with fibroblasts. From these results, it was concluded that hamamelitannin protects murine fibroblasts against external active oxygens by associating with the cell surface through its sugar moiety.