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Cutis Feb 2022
Topics: Dermatitis, Phototoxic; Humans; Methoxsalen; Photosensitizing Agents; Ultraviolet Rays
PubMed: 35659812
DOI: 10.12788/cutis.0462 -
Toxicology Sep 2022Pyrimethamine (PYR) is used to treat parasitic infections including toxoplasmosis, pneumonia and cystoisosporiasis in HIV patients. Various oral medicines have shown...
Pyrimethamine (PYR) is used to treat parasitic infections including toxoplasmosis, pneumonia and cystoisosporiasis in HIV patients. Various oral medicines have shown phototoxicity therefore, we aimed to study the phototoxicity of PYR and its molecular mechanism involving stress responsive lysosomal protein Lamp2 and mitochondrial mediated signaling pathway under normal UVA/B exposure. We found that photodegradation and subsequent photoproduct formation was evident through LCMS/MS analysis. Photosensitized PYR produces ROS that cause damage to DNA, cell membrane and membrane bound organelles in human keratinocytes. PYR triggered cytotoxicity and phototoxicity that was evident through MTT and NRU assay respectively. Intracellular ROS generation caused phosphatidyl serine (PS) translocation in cell membrane, lysosome membrane permeabilization (LMP) and mitochondrial membrane potential (MMP) collapse that was further validated through caspase3 activation. DNA damage was measured as tail DNA formation and cell cycle arrest in G1 phase. Photosensitized PYR induces oxidative stress in the form of overexpression of Lamp2 that ultimately led to cellular apoptosis. Moreover, the effects of UVB were higher than UVA, probably due to its direct interaction with various macromolecules. We propose that photoexcited PYR may be harmful to human health even at normal sunlight exposure. Therefore, protective procedures should be practiced during PYR medication.
Topics: Dermatitis, Phototoxic; HIV Infections; Humans; Keratinocytes; Lysosomes; Phosphatidylserines; Pyrimethamine; Reactive Oxygen Species; Signal Transduction; Sunlight; Ultraviolet Rays
PubMed: 36108988
DOI: 10.1016/j.tox.2022.153320 -
The Science of the Total Environment Dec 2023The increased use of agrochemicals raises concerns about environmental, animal, and mainly human toxicology. The development of New Approach Methodologies (NAMs) for...
The increased use of agrochemicals raises concerns about environmental, animal, and mainly human toxicology. The development of New Approach Methodologies (NAMs) for toxicological risk assessment including new in vitro tests and in silico protocols is encouraged. Although agrochemical mutagenicity testing is well established, a complementary alternative approach may contribute to increasing reliability, with the consequent reduction of false-positive results that lead to unnecessary use of animals in follow-up in vivo testing. Additionally, it is unreasonable to underestimate the phototoxic effects of an accidental dermal exposure to agrochemicals during agricultural work or domestic application in the absence of adequate personal protection equipment, especially in terms of photomutagenicity. In this scenario, we addressed the integration of in vitro and in silico techniques as NAMs to assess the mutagenic and phototoxic potential of agrochemicals. In the present study we used the yno1 S. cerevisiae strain as a biomodel for in vitro assessment of agrochemical mutagenicity, both in the absence and in the presence of simulated sunlight. In parallel, in silico predictions were performed using a combination of expert rule-based and statistical-based models to assess gene mutations and phototoxicity. None of the tested agrochemicals showed mutagenic potential in the two proposed approaches. The Gly and 2,4D herbicides were photomutagenic in the in vitro yeast test despite the negative in silico prediction of phototoxicity. Herein, we demonstrated a novel experimental approach combining both in silico and in vitro experiments to address the complementary investigation of the phototoxicity and (photo)mutagenicity of agrochemicals. These findings shed light on the importance of investigating and reconsidering the photosafety assessment of these products, using not only photocytotoxicity assays but also photomutagenicity assays, which should be encouraged.
Topics: Humans; Animals; Mutagens; Saccharomyces cerevisiae; Agrochemicals; Reproducibility of Results; Risk Assessment; In Vitro Techniques
PubMed: 37748613
DOI: 10.1016/j.scitotenv.2023.167320 -
The Journal of Pediatrics Dec 2021
Topics: Child; Dermatitis, Phototoxic; Female; Ficus; Humans; Plant Leaves; Trees
PubMed: 34428434
DOI: 10.1016/j.jpeds.2021.08.029 -
Journal of Cosmetic Dermatology Dec 2017Bee (Apis mellifera L.) venom (BV) has been used as a cosmetic ingredient owing to its anti-aging, anti-inflammatory, and antibacterial effects. The aim of this study...
OBJECTIVE
Bee (Apis mellifera L.) venom (BV) has been used as a cosmetic ingredient owing to its anti-aging, anti-inflammatory, and antibacterial effects. The aim of this study was to assess the skin safety of BV.
METHODS
For this purpose, skin phototoxicity and sensitization tests were conducted in healthy male Hartley guinea pigs. The animals were divided into three groups (n=5) for the phototoxicity test: G1 (negative control), G2 (BV gel treatment), and G3 (positive control). After specified treatments, the animals were irradiated with ultraviolet A (15 J/cm ). The photosensitivity test was also performed in three groups: G4 (negative control, n=5), G5 (BV gel treatment, n=10), and G6 (positive control, n=5).
RESULTS
Erythema and edema were observed after 24, 48, and 72 hours in the positive control group, but not in the negative control and BV gel groups. Application of BV to the guinea pig skin had no toxic effects on any clinical signs, body weight, or mortality. In addition, it did not evoke a skin reaction in both either the skin phototoxicity and skin photosensitization tests.
CONCLUSION
Therefore, it can be concluded that BV has the potential to be developed as a drug ingredient for topical uses.
Topics: Animals; Bee Venoms; Body Weight; Dermatitis, Photoallergic; Dermatitis, Phototoxic; Edema; Erythema; Guinea Pigs; Male; Ultraviolet Rays
PubMed: 28509378
DOI: 10.1111/jocd.12350 -
Journal of the American Academy of... Feb 2015Voriconazole, an antifungal agent, is associated with various cutaneous reactions, including phototoxicity, accelerated photoaging, and skin cancer. Incidence and risk...
BACKGROUND
Voriconazole, an antifungal agent, is associated with various cutaneous reactions, including phototoxicity, accelerated photoaging, and skin cancer. Incidence and risk factors for these reactions in children have not been well described.
OBJECTIVE
We sought to determine the incidence of and factors associated with phototoxic reactions and nonmelanoma skin cancer in pediatric patients treated with voriconazole.
METHODS
This was a retrospective analysis of 430 pediatric patients treated with voriconazole between 2003 and 2013 at Boston Children's Hospital.
RESULTS
Incidence of phototoxicity was 20% in all children treated with voriconazole and 47% in children treated for 6 months or longer. Factors associated with phototoxicity included white race, cystic fibrosis, cumulative treatment time, and cumulative dose. Four patients (1%) had nonmelanoma skin cancer; all experienced a phototoxic reaction during voriconazole treatment. Of those with phototoxicity, 5% were discontinued on voriconazole, 6% were referred to dermatology, and 26% received counseling about sun protection from their primary physician.
LIMITATIONS
Our study is limited by its retrospective design and potential referral bias associated with a tertiary-care center.
CONCLUSIONS
Voriconazole-associated phototoxicity is relatively common in children and may lead to nonmelanoma skin cancer. However, those with phototoxic reactions are often continued on therapy, rarely referred to dermatology, and infrequently counseled on sun protection.
Topics: Adolescent; Antifungal Agents; Boston; Carcinoma, Squamous Cell; Causality; Child; Comorbidity; Cystic Fibrosis; Dermatitis, Phototoxic; Female; Humans; Immunocompromised Host; Incidence; Male; Mycoses; Retrospective Studies; Risk Factors; Skin Neoplasms; Voriconazole; White People
PubMed: 25481710
DOI: 10.1016/j.jaad.2014.10.023 -
Journal of the American Academy of... Sep 2014
Topics: Anti-Bacterial Agents; Ciprofloxacin; Dermatitis, Phototoxic; Disease Progression; Female; Humans; Stevens-Johnson Syndrome; Young Adult
PubMed: 25128136
DOI: 10.1016/j.jaad.2014.02.033 -
Photochemistry and Photobiology Jul 2021A challenge for cosmetic and dermatologic products is to develop new high-performance and safer anti-aging products based on new compounds to enhance the stability of...
A challenge for cosmetic and dermatologic products is to develop new high-performance and safer anti-aging products based on new compounds to enhance the stability of retinyl palmitate combined with broad-spectrum UV-filters. Consequently, the aim of this work was to evaluate the effects of three often used avobenzone photostabilizers-ethylhexyl methoxycrylene (EHMCR), tris(tetramethylhydroxypiperidinol) citrate (TTMHP) and tris-biphenyl triazine (TBPT)-on the photostability and phototoxicity of the combination of avobenzone (AVO), octyl methoxycinnamate (OMC) and retinyl palmitate (RP). The photostability studies were performed by the exposure of formulations to UVA radiation. The phototoxicity was evaluated by the 3T3 neutral red uptake phototoxic assay (OECD TG 432). The addition of EHMCR, TBPT, and TTMHP in the formulations, with/or without RP, improved the photostability of AVO and RP, but EHMCR was the most effective in stabilizing RP. In the phototoxicity assay, the combinations AVO-OMC containing or not RP showed phototoxic potential. EHMCR and TTMHP reduced the phototoxicity of the combination AVO-OMC, whereas EHMCR also decreased the phototoxicity of the combination containing RP. Therefore, EHMCR might be used to the photostabilization of formulations of AVO-OMC with/or not RP, while TTMHP can be added to this photounstable UV-filter combination.
Topics: Dermatitis, Phototoxic; Diterpenes; Drug Stability; Humans; Propiophenones; Retinyl Esters; Sunscreening Agents; Ultraviolet Rays
PubMed: 33621371
DOI: 10.1111/php.13407 -
Free Radical Biology & Medicine Sep 2019Phototoxic effects of 6,8 dihalogenated quinolones confers to this type of molecules a potential property as photochemotherapeutic agents. Two photodehalogenation...
Phototoxic effects of 6,8 dihalogenated quinolones confers to this type of molecules a potential property as photochemotherapeutic agents. Two photodehalogenation processes seem to be involved in the remarkable photoinduced cellular damage. In this context, a new 6,8 dihalogenated quinolone 1 (1-methyl-6,8-difluoro-4-oxo-7-aminodimethyl-1,4-dihydroquinoline-3-carboxylic acid) was synthetized looking for improving the phototoxic properties of fluoroquinolones (FQ) and to determine the role of the photodegradation pathways in the FQ phototoxicity. With this purpose, fluorescence emissions, laser flash photolysis experiments and photodegradation studies were performed with compound 1 using 1-ethyl-6,8-difluoro-4-oxo-7-aminodimethyl-1,4-dihidroquinoline-3-carboxylic acid (2) and lomefloxacin (LFX) as reference compounds. The shortening of alkyl chain of the N(1) of the quinolone ring revealed a lifetime increase of the reactive aryl cation generated from photolysis of the three FQ and a significant reduction of the FQ photodegradation quantum yield. The fact that these differences were smaller when the same study was done using a hydrogen donor solvent (ethanol-aqueous buffer, 50/50 v/v) evidenced the highest ability of the reactive intermediate arising from 1 to produce intermolecular alkylations. These results were correlated with in vitro 3T3 NRU phototoxicity test. Thus, when Photo-Irritation-Factor (PIF) was determined for 1, 2 and LFX using cytotoxicity profiles of BALB/c 3T3 fibroblasts treated with each compound in the presence and absence of UVA light, a PIF more higher than 30 was obtained for 1 while the values for 2 and LFX were only higher than 8 and 10, respectively. Thereby, the present study illustrates an approach to modulate the photosensitizing properties of FQ with the purpose to improve the chemotherapeutic properties of antitumor quinolones. Moreover, the results obtained in this study also evidence that the key pathway responsible for the phototoxic properties associated with dihalogenated quinolones is the aryl cation generation.
Topics: 3T3 Cells; Animals; Antineoplastic Agents; Dermatitis, Phototoxic; Drug Design; Fluoroquinolones; Halogens; Lasers; Methane; Mice; Mice, Inbred BALB C; Microscopy, Confocal; Photochemistry; Quinolones; Singlet Oxygen
PubMed: 31195085
DOI: 10.1016/j.freeradbiomed.2019.06.010 -
Food and Chemical Toxicology : An... Oct 2020The existing information supports the use of this material as described in this safety assessment. The material (phenylacetaldehyde) was evaluated for genotoxicity,... (Review)
Review
The existing information supports the use of this material as described in this safety assessment. The material (phenylacetaldehyde) was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity, skin sensitization, and environmental safety. Data show that phenylacetaldehyde is not genotoxic and provide a calculated margin of exposure (MOE) > 100 for the repeated dose and developmental and reproductive toxicity endpoints. Data from phenylacetaldehyde provided a No Expected Sensitization Induction Level (NESIL) of 590 μg/cm for the skin sensitization endpoint. The local respiratory toxicity endpoint was completed using the threshold of toxicological concern (TTC) for a Cramer Class I material, and the exposure to phenylacetaldehyde was below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). The phototoxicity/photoallergenicity endpoint was completed based on data and ultraviolet (UV) spectra; phenylacetaldehyde is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; phenylacetaldehyde was not found 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: Acetaldehyde; Animals; Dermatitis, Phototoxic; Humans; Mutagenicity Tests; Perfume; Registries; Risk Assessment
PubMed: 32835729
DOI: 10.1016/j.fct.2020.111658