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Toxicology and Applied Pharmacology Jun 2024The OECD has approved two similar methods for testing the phototoxic potency of chemicals. The first method, OECD 432, is based on the cytotoxicity properties of...
The OECD has approved two similar methods for testing the phototoxic potency of chemicals. The first method, OECD 432, is based on the cytotoxicity properties of materials to the mouse 3 T3 (clone A31) cell line (fibroblasts) after exposure to light. The second method, OECD 498, is based on the same properties but using reconstructed human epidermis - EpiDerm (stratified keratinocytes). The aim of this study was to compare these two methods using statistical tests (specificity, sensitivity, negative predictive value, positive predictive value and accuracy) and non-statistical characteristics (e.g. price and experimental duration, amount of material, level of complications, cell type, irradiation dose). Both tests were performed according to the relevant guidelines using the same 11 control substances. Higher performance values were observed for OECD 432 in both phototoxic and non-phototoxic classifications. The accuracy of OECD 432 was 90.9%, while that of OECD 498 was 72.7%. OECD 432 was also shorter and less expensive. On the other hand, OECD 498 was less complicated, and used human cells with stratum corneum, which better reflects real skin. This method can also be used with oily substances that are poorly soluble in water. However, both methods are important for testing the phototoxic properties of materials, and can be used alone or in a tiered strategy.
PubMed: 38914165
DOI: 10.1016/j.taap.2024.117014 -
Toxicological Research Jul 2024Cocamidopropyl betaine (CAPB) is a surfactant derived from coconut oil that is widely used in cosmetics and personal products for several purposes, such as a surfactant,...
Cocamidopropyl betaine (CAPB) is a surfactant derived from coconut oil that is widely used in cosmetics and personal products for several purposes, such as a surfactant, foam booster, mildness, and viscosity control. Cocamidopropyl betaine is used at concentrations up to 30% in cosmetics. The acute toxicity, skin irritation, eye irritation, skin sensitization, repeated dose toxicity, genotoxicity, carcinogenicity, and phototoxicity of cocamidopropyl betaine were evaluated. Cocamidopropyl betaine was observed to induce mild skin irritation, eye irritation and skin sensitization. The NOAEL of cocamidopropyl betaine was determined to be 250 mg/kg/day based on the results of a 92-day repeated-dose oral toxicity study in rats. The systemic exposure dose of cocamidopropyl betaine was estimated to range from 0.00120 to 0.93195 mg/kg/day when used in cosmetic products. The margin of safety of cocamidopropyl betaine was calculated to be greater than 100 when used at a maximum concentration of 6% in leave-on products and 30% in rinse-off products, suggesting that its use in cosmetic products is safe under current usage conditions.
PubMed: 38911545
DOI: 10.1007/s43188-024-00243-2 -
Alternatives To Laboratory Animals :... Jun 2024Phototoxicity testing is crucial for evaluating the potential harmful effects of pharmaceuticals and chemicals on human skin when exposed to sunlight. Traditional...
Phototoxicity testing is crucial for evaluating the potential harmful effects of pharmaceuticals and chemicals on human skin when exposed to sunlight. Traditional models involving mice, rats, guinea pigs, as well as assays such as the 3T3 Neutral Red Uptake phototoxicity assay and methods based on the use of reconstructed human epidermis, have been established for phototoxicity testing. While these approaches are extremely valuable, they are costly in terms of both time and resources. Consequently, approaches based on the use of predictive software tools can offer more rapid and cost-effective phototoxicity screening solutions. With this goal in mind, the current study evaluated two tools - Derek Nexus 6.1.0/Derek Knowledge Base 2020 1.0 (Lhasa Limited, UK) and the QSAR Toolbox (v 4.5) developed by the Organisation for Economic Co-operation and Development (OECD) - for their capacity to predict the phototoxicity of several substances from diverse classes. Derek Nexus and the QSAR Toolbox were both found to be very useful for predicting the phototoxicity of drugs and other chemicals. Derek Nexus predicted phototoxicity of the compounds, with a sensitivity of 63%, specificity of 93%, Positive Predictive Values of 90% and Negative Predictive Value of 69%, overall accuracy of 77% and balanced accuracy of 78%. The QSAR Toolbox achieved sensitivity of 73%, specificity of 85%, Positive Predictive Value of 85% and Negative Predictive Value of 74%, overall accuracy of 79% and balanced accuracy of 79%. The results show that Derek Nexus and the QSAR Toolbox can be usefully incorporated in the workflow of phototoxicity testing for pharmaceuticals and chemicals.
PubMed: 38910363
DOI: 10.1177/02611929241256040 -
Photodiagnosis and Photodynamic Therapy Jun 2024Photodynamic therapy (PDT) has been utilized as a promising alternative cancer treatment due to its minimum invasiveness over the years. Exogenous 5-aminolevulinic acid...
BACKGROUND
Photodynamic therapy (PDT) has been utilized as a promising alternative cancer treatment due to its minimum invasiveness over the years. Exogenous 5-aminolevulinic acid (ALA) triggers protoporphyrin IX (PpIX) accumulation, which happens in cancer cells. However, certain types of cancer exhibit reduced effectiveness in the PpIX accumulation mechanism. This study aimed to determine the effect of ALA-PDT combination with hemin on gastric carcinoma TMK-1 cells.
METHODS
This study utilized TMK-1 gastric cancer cell line to evaluate PpIX, ROS, and Fe accumulation following the administration of ALA, hemin, and a combination of ALA and hemin PDT. We also evaluate the mRNA expressions related to iron homeostasis and treatment impacts on cell viability.
RESULTS
The co-addition of ALA and hemin PDT for 4 hours of treatment resulted in a significant decrease in cell viability by up to 18%. While ALA-PDT enhanced PpIX metabolism, the addition of hemin influenced both the production of reactive oxygen species (ROS) and cellular iron homeostasis by inducing Fe accumulation and affecting mRNA levels of IRP, Tfr1, Ferritin, NFS1, and SDHB.
CONCLUSION
These findings suggest that the addition of ALA and hemin enhances phototoxicity in TMK-1 cells. The combination of ALA and hemin with PDT induces cell death, evidenced by increased cytotoxicity properties such as PpIX and ROS, along with significant changes in TMK-1 gastric cancer iron homeostasis. Therefore, the combination of ALA and hemin could be one of the alternatives in photodynamic therapy for cancer in the future.
PubMed: 38901716
DOI: 10.1016/j.pdpdt.2024.104253 -
Photochemistry and Photobiology Jun 2024Exposure to phototoxicants and photosensitizers can result in the generation of reactive oxygen species (ROS), leading to oxidative stress, DNA damage, and various...
Exposure to phototoxicants and photosensitizers can result in the generation of reactive oxygen species (ROS), leading to oxidative stress, DNA damage, and various skin-related issues such as aging, allergies, and cancer. While several photo-protectants offer defense against ultraviolet radiation (UV-R), their effectiveness is often limited by photo-instability. Sunset Yellow (SY), an FDA-approved food dye, possesses significant UV-R and visible light absorption properties. However, its photoprotective potential has remained unexplored. Our investigation reveals that SY exhibits remarkable photostability for up to 8 h under both UV-R and sunlight. Notably, SY demonstrates the ability to quench ROS, including singlet oxygen (O), superoxide radicals ( ), and hydroxyl radicals (·OH) induced by rose bengal, riboflavin and levofloxacin, respectively. Moreover, SY proves effective in protecting against the apoptotic and necrotic cell death induced by the phototoxicant chlorpromazine (CPZ) in HaCaT cells. Further, it was observed that SY imparts photoprotection by inhibiting intracellular ROS generation and calcium release. Genotoxicity evaluation provides additional evidence supporting SY's photoprotective effects against CPZ-induced DNA damage. In conclusion, these findings underscore the potential of SY as a promising photoprotective agent against the toxic hazards induced by phototoxicants, suggesting its prospective application in the formulation of broad-spectrum sunscreens.
PubMed: 38899585
DOI: 10.1111/php.13966 -
RSC Advances Jun 2024In recent years, photodynamic therapy (PDT) has garnered significant attention in cancer treatment due to its increased potency and non-invasiveness compared to...
In recent years, photodynamic therapy (PDT) has garnered significant attention in cancer treatment due to its increased potency and non-invasiveness compared to conventional therapies. Active-targeted delivery of photosensitizers (PSs) is a mainstay strategy to significantly reduce its off-target toxicity and enhance its phototoxic efficacy. The anti-melanoma inhibitory activity (MIA) antibody is a targeting biomolecule that can be integrated into a nanocarrier system to actively target melanoma cells due to its specific binding to MIA antigens that are highly expressed on the surface of melanoma cells. Gold nanoparticles (AuNPs) are excellent nanocarriers due to their ability to encapsulate a variety of therapeutics, such as PSs, and their ability to bind with targeting moieties for improved bioavailability in cancer cells. Hence, we designed a nanobioconjugate (NBC) composed of zinc phthalocyanine tetrasulfonic acid (ZnPcS), AuNPs and anti-MIA Ab to improve ZnPcS bioavailability and phototoxicity in two and three-dimensional tumour models. In summary, we demonstrated that this nanobioconjugate showed significant inhibitory effects on both melanoma models due to increased ROS yields and bioavailability of the melanoma cells compared to free ZnPcS
PubMed: 38895533
DOI: 10.1039/d4ra03858d -
Trends in Molecular Medicine Jun 2024Protoporphyrias are caused by pathogenic variants in genes encoding enzymes involved in heme biosynthesis. They induce the accumulation of a hydrophobic phototoxic... (Review)
Review
Protoporphyrias are caused by pathogenic variants in genes encoding enzymes involved in heme biosynthesis. They induce the accumulation of a hydrophobic phototoxic compound, protoporphyrin (PPIX), in red blood cells (RBCs). PPIX is responsible for painful cutaneous photosensitivity, which severely impairs quality of life. Hepatic elimination of PPIX increases the risk of cholestatic liver disease, requiring lifelong monitoring. Treatment options are scarce and mainly limited to supportive care such as protection from visible light. Here, we review the pathophysiology of protoporphyrias, their diagnosis, and current recommendations for medical care. We discuss new therapeutic strategies, some of which are currently undergoing clinical trials and are likely to radically alter the severity of the disease in the years to come.
PubMed: 38890030
DOI: 10.1016/j.molmed.2024.05.006 -
Analytical Chemistry Jun 2024Single-molecule localization microscopy (SMLM) requires high-intensity laser irradiation, typically exceeding kW/cm, to yield a sufficient photon count. However, this...
Single-molecule localization microscopy (SMLM) requires high-intensity laser irradiation, typically exceeding kW/cm, to yield a sufficient photon count. However, this intense visible light exposure incurs substantial cellular toxicity, hindering its use in living cells. Here, we developed a class of near-infrared (NIR) spontaneously blinking fluorophores for SMLM. These NIR fluorophores are a combination of rhodamine spirolactams and merocyanine derivatives, where the rhodamine spirolactam component converts between a bright and dark state based on pH-dependent spirocyclization and merocyanine derivatives shift the excitation wavelength into the infrared. Single-molecule characterizations demonstrated their potential for SMLM. At a moderate power density of 3.93 kW/cm, these probes exhibit duty cycle as low as 0.18% and an emission rate as high as 26,700 photons/s. Phototoxicity assessment under single-molecule imaging conditions reveals that NIR illumination (721 nm) minimizes harm to living cells. Employing these NIR fluorophores, we successfully captured time-lapse super-resolution tracking of mitochondria at a Fourier ring correlation (FRC) resolution of 69.4 nm and reconstructed the ultrastructures of endoplasmic reticulum (ER) in living cells.
PubMed: 38889184
DOI: 10.1021/acs.analchem.4c02445 -
Advanced Science (Weinheim,... Jun 2024Activatable type I photosensitizers are an effective way to overcome the insufficiency and imprecision of photodynamic therapy in the treatment of hypoxic tumors,...
Activatable type I photosensitizers are an effective way to overcome the insufficiency and imprecision of photodynamic therapy in the treatment of hypoxic tumors, however, the incompletely inhibited photoactivity of pro-photosensitizer and the limited oxidative phototoxicity of post-photosensitizer are major limitations. It is still a great challenge to address these issues using a single and facile design. Herein, a series of totally caged type I pro-photosensitizers (Pro-I-PSs) are rationally developed that are only activated in tumor hypoxic environment and combine two oxygen-independent therapeutic mechanisms under single-pulse laser irradiation to enhance the phototherapeutic efficacy. Specifically, five benzophenothiazine-based dyes modified with different nitroaromatic groups, BPN 1-5, are designed and explored as latent hypoxia-activatable Pro-I-PSs. By comparing their optical responses to nitroreductase (NTR), it is identified that the 2-methoxy-4-nitrophenyl decorated dye (BPN 2) is the optimal Pro-I-PSs, which can achieve NTR-activated background-free fluorescence/photoacoustic dual-modality tumor imaging. Furthermore, upon activation, BPN 2 can simultaneously produce an oxygen-independent photoacoustic cavitation effect and a photodynamic type I process at single-pulse laser irradiation. Detailed studies in vitro and in vivo indicated that BPN 2 can effectively induce cancer cell apoptosis through synergistic effects. This study provides promising potential for overcoming the pitfalls of hypoxic-tumor photodynamic therapy.
PubMed: 38885361
DOI: 10.1002/advs.202400462 -
Italian Journal of Dermatology and... Jun 2024Despite the promising results in terms of effectiveness of anticancer treatments, a wide range of dermatologic adverse reactions have been reported. Among them, skin...
INTRODUCTION
Despite the promising results in terms of effectiveness of anticancer treatments, a wide range of dermatologic adverse reactions have been reported. Among them, skin photosensitivity, defined as a range of dermatologic conditions caused or exacerbated by sunlight exposure, is an emerging adverse event.
EVIDENCE ACQUISITION
A review of the current literature was performed to report the most characteristic phototoxic and photoallergic reactions associated with anticancer therapies, as well as other characteristic manifestations potentially related to photo-exposure, including UV recall, vitiligo-like reactions, drug-induced cutaneous lupus erythematosus, and UV-induced hyperpigmentation.
EVIDENCE SYNTHESIS
A total of 30 manuscripts were collected in the present review, reporting several phototoxic and photoallergic reactions associated with anticancer therapies.
CONCLUSIONS
Photosensitivity reactions are an increasing challenge in cancer management. The raising awareness about this adverse event has increased the identification of potential photosensitizing drugs as well as its prevention and the management. However, more studies are required to improve the knowledge of this cutaneous toxicity and to define a personalized treatment strategy.
PubMed: 38884533
DOI: 10.23736/S2784-8671.24.07782-X