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International Journal of Molecular... Aug 2023Skin photoaging due to ultraviolet B (UVB) exposure generates reactive oxygen species (ROS) that increase matrix metalloproteinase (MMP). Chlorin e6-photodynamic therapy...
Skin photoaging due to ultraviolet B (UVB) exposure generates reactive oxygen species (ROS) that increase matrix metalloproteinase (MMP). Chlorin e6-photodynamic therapy (Ce6-PDT), in addition to being the first-line treatment for malignancies, has been shown to lessen skin photoaging, while curcumin is well known for reducing the deleterious effects of ROS. In the current study, PDT with three novel Ce6-curcumin derivatives, a combination of Ce6 and curcumin with various linkers, including propane-1,3-diamine for Ce6-propane-curcumin; hexane-1,6-diamine for Ce6-hexane-curcumin; and 3,3'-((oxybis(ethane-2,1-diyl))bis(oxy))bis(propan-1-amine) for Ce6-dipolyethylene glycol (diPEG)-curcumin, were studied for regulation of UVB-induced photoaging on human skin fibroblast (Hs68) and mouse embryonic fibroblast (BALB/c 3T3) cells. We assessed the antiphotoaging effects of Ce6-curcumin derivatives on cell viability, antioxidant activity, the mechanism of matrix metalloproteinase-1 and 2 (MMP-2) expression, and collagen synthesis in UVB-irradiated in vitro models. All three Ce6-curcumin derivatives were found to be non-phototoxic in the neutral red uptake phototoxicity test. We found that Ce6-hexane-curcumin-PDT and Ce6-propane-curcumin-associated PDT exhibited less cytotoxicity in Hs68 and BALB/c 3T3 fibroblast cell lines compared to Ce6-diPEG-curcumin-PDT. Ce6-diPEG-curcumin and Ce6-propane-curcumin-associated PDT showed superior antioxidant activity in Hs68 cell lines. Further, in UVB-irradiated in vitro models, the Ce6-diPEG-curcumin-PDT greatly attenuated the expression levels of MMP-1 and MMP-2 by blocking mitogen-activated protein kinases (MAPKs), activator protein 1 (AP-1), and tumor necrosis factor-α (NF-κB) signaling. Moreover, Ce6-diPEG-curcumin effectively inhibited inflammatory molecules, such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, while accelerating collagen synthesis. These results demonstrate that Ce6-diPEG-curcumin may be a potential therapy for treating skin photoaging.
Topics: Animals; Mice; Humans; Curcumin; Hexanes; Matrix Metalloproteinase 2; Antioxidants; Propane; Reactive Oxygen Species; Fibroblasts; Dermatitis, Phototoxic; Glycols; Photochemotherapy; Collagen
PubMed: 37686273
DOI: 10.3390/ijms241713468 -
Food and Chemical Toxicology : An... Oct 2020The existing information supports the use of this material as described in this safety assessment. Decanoic acid was evaluated for genotoxicity, repeated dose toxicity,... (Review)
Review
The existing information supports the use of this material as described in this safety assessment. Decanoic acid was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data on the target material and from read-across analog nonanoic acid (CAS # 112-05-0) show that decanoic acid is not expected to be genotoxic. Data on read-across analog octanoic acid (CAS # 124-07-2) provide a calculated MOE >100 for the repeated dose and reproductive toxicity endpoints. Based on the existing data, decanoic acid does not present a concern for skin sensitization under the current, declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on UV spectra; decanoic acid is not expected to be phototoxic/photoallergenic. The local respiratory toxicity endpoint was evaluated using the TTC for a Cramer Class I material, and the exposure to decanoic acid is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; decanoic acid was found not to be PBT as per the IFRA Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., PEC/PNEC), are <1.
Topics: Animals; Decanoic Acids; Dermatitis, Phototoxic; Humans; Mutagenicity Tests; Perfume; Registries; Risk Assessment
PubMed: 32640335
DOI: 10.1016/j.fct.2020.111465 -
Clinics in Dermatology 2015Patients with photosensitive disorders of the skin may present with ocular manifestations that are evident at birth or may be manifested later with progression of the... (Review)
Review
Patients with photosensitive disorders of the skin may present with ocular manifestations that are evident at birth or may be manifested later with progression of the disorder. Dermatologists should be able to recognize these and appropriately refer patients for further management. Ocular involvement associated with immunologically mediated photodermatoses, drug- and chemical-induced photosensitivity, photodermatoses associated with defective DNA repair/chromosome instability, and photoaggravated dermatoses are reviewed. Photodermatoses are commonly classified into four general groups: (1) immunologically mediated photodermatoses; (2) drug- and chemical-induced photosensitivity; (3) photodermatoses associated with defective DNA repair/chromosome instability; and (4) photoaggravated dermatoses. Photodermatoses in these groups with ocular involvement will be discussed. In addition, skin diseases associated with photophobia are also described.
Topics: Comorbidity; Dermatitis, Photoallergic; Dermatitis, Phototoxic; Eye Diseases; Female; Humans; Incidence; Male; Photosensitivity Disorders; Prognosis; Risk Assessment; Severity of Illness Index
PubMed: 25704944
DOI: 10.1016/j.clindermatol.2014.10.016 -
Food and Chemical Toxicology : An... Jul 2021The existing information supports the use of this material as described in this safety assessment. Hexadeca-1,5-lactone was evaluated for genotoxicity, repeated dose... (Review)
Review
The existing information supports the use of this material as described in this safety assessment. Hexadeca-1,5-lactone was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from the target material and read-across analog hydroxynonanoic acid, δ-lactone (CAS # 3301-94-8) show that hexadeca-1,5-lactone is not expected to be genotoxic. Data from analog δ-decalactone (CAS # 705-86-2) provide a calculated Margin of Exposure (MOE) > 100 for the repeated dose and reproductive toxicity endpoints. Data from analog δ-octalactone (CAS # 698-76-0) show that there are no safety concerns for skin sensitization under the current declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; hexadeca-1,5-lactone is not expected to be phototoxic/photoallergenic. The local respiratory toxicity endpoint was evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material; exposure is below the TTC (1.4 mg/day). For the hazard assessment based on the screening data, hexadeca-1,5-lactone is not Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards. Hexadeca-1,5-lactone could not be risk screened as there were no reported volumes of use for either North America or Europe in the 2015 IFRA Survey.
Topics: Animals; Bacteria; Consumer Product Safety; Endpoint Determination; Humans; Lactones; Odorants; Perfume; Risk Assessment; Stereoisomerism
PubMed: 33839218
DOI: 10.1016/j.fct.2021.112181 -
JAAD Case Reports Mar 2022
PubMed: 35146099
DOI: 10.1016/j.jdcr.2021.12.019 -
Journal of Drugs in Dermatology : JDD Oct 2022Tapinarof (VTAMA®; Dermavant Sciences, Inc.) is a novel, non-steroidal, topical, aryl hydrocarbon receptor agonist, FDA approved for psoriasis treatment and under... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Tapinarof (VTAMA®; Dermavant Sciences, Inc.) is a novel, non-steroidal, topical, aryl hydrocarbon receptor agonist, FDA approved for psoriasis treatment and under investigation for atopic dermatitis treatment as a 1% cream formulation for once-daily (QD) application.
OBJECTIVE
Evaluate cumulative skin irritation, sensitization, and photoallergic and phototoxic potential of tapinarof cream 1% across a range of dosing frequencies and conditions.
METHODS
We conducted 4 randomized, controlled, phase 1 trials of topical tapinarof cream 1% vs vehicle or other appropriate controls in healthy adults. Cumulative skin irritation was assessed following QD application for 21 days under fully occlusive patch conditions. Contact sensitization, photoallergenicity, and phototoxicity were assessed under semi-occlusive patch conditions. The contact sensitization and photoallergenicity trials used an induction phase of repeated applications followed by a 2-week rest period and a 1-time challenge, with rechallenge if responses indicated sensitization/photosensitization; the phototoxicity trial comprised a single application. Ultraviolet A and B irradiation was used to assess photoallergenicity/toxicity.
RESULTS
376 participants were randomized across the 4 trials. In the cumulative irritation trial, tapinarof cream 1% QD was classified as having a slight potential for very mild cumulative irritation under the exaggerated test conditions of repeated dosing for 21 days. There was no evidence of sensitization, photosensitization, or phototoxicity. Tapinarof was well tolerated and there was a low discontinuation rate across all trials.
CONCLUSIONS
Tapinarof cream 1% was well tolerated, non-sensitizing, non-phototoxic, and non-photoallergic, with no evidence of clinically meaningful cumulative skin irritation in 4 dermal safety trials in healthy adults.
TRIAL REGISTRATION
IND 104601 J Drugs Dermatol. 2022;21(10):1084-1090. doi:10.36849/JDD.6627R1.
Topics: Adult; Dermatitis, Photoallergic; Dermatitis, Phototoxic; Humans; Receptors, Aryl Hydrocarbon; Resorcinols; Skin Cream
PubMed: 36219046
DOI: 10.36849/JDD.6627 -
International Journal of Cosmetic... Aug 2018Cinnamic acid derivatives are widely used in cosmetics and possess various functions. This group of compounds includes both naturally occurring and synthetic substances.... (Review)
Review
Cinnamic acid derivatives are widely used in cosmetics and possess various functions. This group of compounds includes both naturally occurring and synthetic substances. On the basis of the Cosmetic Ingredient Database (CosIng) and available literature, this review summarizes their functions in cosmetics, including their physicochemical and biological properties as well as reported adverse effects. A perfuming function is typical of many derivatives of cinnamaldehyde, cinnamyl alcohol, dihydrocinnamyl alcohol and cinnamic acid itself; these substances are commonly used in cosmetics all over the world. Some of them show allergic and photoallergic potential, resulting in restrictions in maximum concentrations and/or a requirement to indicate the presence of some substances in the list of ingredients when their concentrations exceed certain fixed values in a cosmetic product. Another important function of cinnamic acid derivatives in cosmetics is UV protection. Ester derivatives such as ethylhexyl methoxycinnamate (octinoxate), isoamyl p-methoxycinnamte (amiloxiate), octocrylene and cinoxate are used in cosmetics all over the world as UV filters. However, their maximum concentrations in cosmetic products are restricted due to their adverse effects, which include contact and a photocontact allergies, phototoxic contact dermatitis, contact dermatitis, estrogenic modulation and generation of reactive oxygen species. Other rarely utilized functions of cinnamic acid derivatives are as an antioxidant, in skin conditioning, hair conditioning, as a tonic and in antimicrobial activities. Moreover, some currently investigated natural and synthetic derivatives of cinnamic acid have shown skin lightening and anti-ageing properties. Some of them may become new cosmetic ingredients in the future. In particular, 4-hydroxycinnamic acid, which is currently indexed as a skin-conditioning cosmetics ingredient, has been widely tested in vitro and in vivo as a new drug candidate for the treatment of hyperpigmentation.
Topics: Animals; Anti-Infective Agents; Antioxidants; Cinnamates; Cosmetics; Humans; Melanins; Odorants; Radiation-Protective Agents; Rats; Ultraviolet Rays
PubMed: 29870052
DOI: 10.1111/ics.12471 -
Food and Chemical Toxicology : An... Oct 2020Furfuryl thioacetate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin... (Review)
Review
Furfuryl thioacetate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that furfuryl thioacetate is not genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the threshold of toxicological concern (TTC) for a Cramer Class III material, and the exposure to furfuryl thioacetate is below the TTC (0.0015 mg/kg/day, 0.0015 mg/kg/day, and 0.47 mg/day, respectively). The skin sensitization endpoint was completed using the dermal sensitization threshold (DST) for reactive materials (64 μg/cm); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; furfuryl thioacetate is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; furfuryl thioacetate was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.
Topics: Animals; Dermatitis, Phototoxic; Humans; Mutagenicity Tests; Perfume; Registries; Risk Assessment
PubMed: 32781229
DOI: 10.1016/j.fct.2020.111615 -
Anais Brasileiros de Dermatologia 2022The therapeutic approach to metastatic melanoma has revolutionized the clinical course of this disease. Since 2011, different immunotherapeutic drugs have been approved....
The therapeutic approach to metastatic melanoma has revolutionized the clinical course of this disease. Since 2011, different immunotherapeutic drugs have been approved. Nivolumab is a humanized immunoglobulin IgG4 monoclonal antibody that binds to the PD-1 receptor, blocking its interaction with his ligand PD-L1. The authors present a new case of photosensitivity induced by nivolumab. The photo exposed distribution of the eruption, the sun exposure prior to the beginning of the eruption, and the chronological relationship with the beginning of the treatment are data that have allowed us to confirm the suspected clinical diagnosis.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Dermatitis, Phototoxic; Exanthema; Humans; Melanoma; Nivolumab; Programmed Cell Death 1 Receptor
PubMed: 35811193
DOI: 10.1016/j.abd.2021.07.007 -
Photochemistry and Photobiology Mar 2023Photodynamic therapy can be useful for the eradication of malignant cells at sites that are accessible to light delivery. There are few adverse effects, with many...
Photodynamic therapy can be useful for the eradication of malignant cells at sites that are accessible to light delivery. There are few adverse effects, with many clinical reports indicating that PDT has curative potential. Patients with minimal disease, where success is more likely, are also sought by those promoting other protocols. New photosensitizing agents that initiate light-catalyzed reactions continue to be discovered. Reports describing advances in understanding fundamental aspects of photobiology are always of interest. But, implications for treatment of neoplasia and other diseases are not always justified, especially when poorly penetrating wavelengths of light are employed, often at very high light doses. Efficacy is sometimes estimated by protocols that may not accurately measure photokilling. Many reports claiming potential clinical relevance for in vitro observations are based on a limited understanding of the determinants of clinical efficacy. The future of photodynamic therapy depends on an appreciation of what can be accomplished, especially when used with other modalities, but will also depend on the goals and interests of granting agencies, pharmaceutical groups, and clinical personnel. This commentary is intended to provide some thoughts on current research efforts, especially where clinical implications are suggested, hinted at or otherwise implied.
Topics: Humans; Photochemotherapy; Photosensitizing Agents; Dermatitis, Phototoxic; Neoplasms; Treatment Outcome
PubMed: 35290667
DOI: 10.1111/php.13616