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BMJ Case Reports Mar 2020
Topics: Agricultural Workers' Diseases; Dermatitis, Phototoxic; Ficus; Furocoumarins; Humans; Male; Middle Aged; Trees
PubMed: 32139449
DOI: 10.1136/bcr-2019-233392 -
Pharmaceutics Nov 2020Photosensitivity induced by drugs is a widely experienced problem, concerning both molecule design and clinical practice. Indeed, photo-induced cutaneous eruptions... (Review)
Review
Photosensitivity induced by drugs is a widely experienced problem, concerning both molecule design and clinical practice. Indeed, photo-induced cutaneous eruptions represent one of the most common drug adverse events and are frequently an important issue to consider in the therapeutic management of patients. Phototoxicity and photoallergy are the two different pathogenic mechanisms involved in photosensitization. Related cutaneous manifestations are heterogeneous, depending on the culprit drug and subject susceptibility. Here we report an updated review of the literature with respect to pathogenic mechanisms of photosensitivity, clinical manifestations, patient management, and prediction and evaluation of drug-induced photosensitivity. We present and discuss principal groups of photosensitizing drugs (antimicrobials, nonsteroidal anti-inflammatory drugs, anti-hypertensives, anti-arrhythmics, cholesterol, and glycemia-lowering agents, psychotropic drugs, chemotherapeutics, etc.) and their main damage mechanisms according to recent evidence. The link between the drug and the cutaneous manifestation is not always clear; more investigations would be helpful to better predict drug photosensitizing potential, prevent and manage cutaneous adverse events and find the most appropriate alternative therapeutic strategy.
PubMed: 33213076
DOI: 10.3390/pharmaceutics12111104 -
Biomedicine & Pharmacotherapy =... Nov 2023Talazoparib (TLZ) is a poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor employed for the treatment of breast cancer. This drug displays an absorption band...
Talazoparib (TLZ) is a poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor employed for the treatment of breast cancer. This drug displays an absorption band in the UVA region, and therefore investigation of the possible phototoxic side-effects associated to its administration results of enormous relevance. In this context, we describe here a photochemical and photobiological study to ascertain the photosafety profile of TLZ. Concerning transient species, the singlet and triplet excited states of TLZ were detected by fluorescence (λ = 440 nm) and laser flash photolysis experiments (λ = 400 nm), respectively. Remarkably, TLZ irradiation with UVA light in aqueous solution resulted in formation of a stable photooxidated product, TLZ-P, whose absorption band is extended until the visible region. From in vitro experiments, phototoxicity was revealed for the parent drug by neutral red uptake (NRU) assays, with a PIF value of ca 7; besides, TLZ induced formation of reactive oxygen species (ROS) and produced significant damage to both proteins and DNA. By contrast, the singlet and triplet excited states of TLZ-P were not detected, and no photodamage was observed in the NRU experiments. Overall, the results indicate that TLZ induces phototoxicity, whereas its photoproduct exhibits photosafety.
Topics: Humans; Poly(ADP-ribose) Polymerase Inhibitors; Dermatitis, Phototoxic; Light; Reactive Oxygen Species; Photosensitizing Agents; Pharmaceutical Preparations
PubMed: 37793275
DOI: 10.1016/j.biopha.2023.115593 -
Journal of Photochemistry and... Apr 2020Recent studies focus on usage of blue light of λ = 450 nm in combination with photosensitizers to treat surface skin disorders, including cancers. In search of...
Recent studies focus on usage of blue light of λ = 450 nm in combination with photosensitizers to treat surface skin disorders, including cancers. In search of convenient therapeutic factor we studied riboflavin analogue 3-methyl-tetraacetylriboflavin (3MeTARF) as potential sensitizer. Riboflavin (Rfl) itself, non -toxic in the darkness, upon absorption of UVA and blue light, may act as photosensitizer. However, Rfl efficiency is limited due to its susceptibility to photodecomposition. Riboflavin's acetylated analogue, 3MeTARF, bears substituents in ribose chain, which inhibit intramolecular processes leading to degradation. Upon excitation, this compound, reveals higher photochemical resistance, remaining a good singlet oxygen generator. Thus, being more stable as the sensitizer, might be much more efficient in photodynamic processes. The objective of undertaken study was to elucidate mechanisms of 3MeTARF photoreactivity under the irradiation with blue light in comparison to its mater compound, riboflavin. We approached this goal by using spectroscopic methods, like direct singlet oxygen phosphorescence detection at 1270 nm, EPR spin trapping and oximetry. Additionally, we tested both riboflavin and 3MeTARF phototoxicity against melanoma cells (WM115) and we studied mechanism of photodynamic cell death, as well. Moreover, 3MeTARF induces apoptosis in melanoma cells at ten times lower concentration than riboflavin itself. Our studies confirmed that 3MeTARF remains stable upon blue light activation and is more efficient photosensitizer than Rfl.
Topics: Cell Line, Tumor; Cell Survival; Dermatitis, Phototoxic; Humans; Hydrogen Peroxide; Light; Radiation-Sensitizing Agents; Riboflavin; Singlet Oxygen
PubMed: 32065959
DOI: 10.1016/j.jphotobiol.2020.111820 -
Biochimica Et Biophysica Acta May 2011The mitochondrial permeability transition is an increase of permeability of the inner mitochondrial membrane to ions and solutes with an exclusion size of about 1500Da.... (Review)
Review
The mitochondrial permeability transition is an increase of permeability of the inner mitochondrial membrane to ions and solutes with an exclusion size of about 1500Da. It is generally accepted that the permeability transition is due to opening of a high-conductance channel, the permeability transition pore. Although the molecular nature of the permeability transition pore remains undefined, a great deal is known about its regulation and role in pathophysiology. This review specifically covers the characterization of the permeability transition pore by chemical modification of specific residues through photoirradiation of mitochondria after treatment with porphyrins. The review also illustrates the basic principles of the photodynamic effect and the mechanisms of phototoxicity and discusses the unique properties of singlet oxygen generated by specific porphyrins in discrete mitochondrial domains. These experiments provided remarkable information on the role, interactions and topology of His and Cys residues in permeability transition pore modulation and defined an important role for the outer membrane 18kDa translocator protein (formerly known as the peripheral benzodiazepine receptor) in regulation of the permeability transition.
Topics: Animals; Dermatitis, Phototoxic; Humans; Light; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Photosensitizing Agents; Porphyrins; Receptors, GABA; Singlet Oxygen
PubMed: 21377443
DOI: 10.1016/j.bbabio.2011.02.012 -
Molecules (Basel, Switzerland) Aug 2023Thienopyrimidines are structural analogs of quinazolines, and the creation of new 2-alkyl derivatives of ethyl 4-aminothienopyrimidine-6-carboxylates for the study of...
Thienopyrimidines are structural analogs of quinazolines, and the creation of new 2-alkyl derivatives of ethyl 4-aminothienopyrimidine-6-carboxylates for the study of their anti-proliferative properties is of great pharmacological interest. Some 2-alkyl-4-amino-thieno[2,3-]pyrimidines - were synthesized, and their cyto- and phototoxicity against BALB 3T3 cells were established by an in vitro 3T3 NRU test. The obtained results indicate that the tested compounds are not cytotoxic or phototoxic, and that they are appropriate to be studied for their anti-proliferative and anti-tumor properties. The anti-proliferative potential of the compounds was investigated on MCF-7 and MDA-MB-231 cancer cells, as well as a MCF-10A cell line (normal human mammary epithelial cells). The most toxic to MCF-7 was thienopyrimidine with IC 13.42 μg/mL (IC 0.045 μM), followed by compound (IC 28.89 μg/mL or IC 0.11 μM). The thienopyrimidine revealed higher selectivity to MCF-7 and lower activity (IC 367 μg/mL i.e., 1.4 μM) than compound with MCF-10A cells. With respect to MDA-MB-231 cells, ester manifested the highest effect with IC 52.56 μg/mL (IC 0.16 μM), and 2-ethyl derivative revealed IC 62.86 μg/mL (IC 0.24 μM). It was estimated that the effect of the substances on the cell cycle progression was due to cell cycle arrest in the G2 stage for MDA-MB-231, while arrest in G1 was detected for the estrogen (ER)-positive MCF-7 cell line. The tested compound's effects on the change of the zeta potential in the tumorigenic cells utilized in this study were determined. The calculation which we performed of the physicochemical properties and pharmacokinetic parameters influencing the biological activity suggested high intestinal absorption, as well as drug-likeness.
Topics: Animals; Mice; Humans; Estrogens; BALB 3T3 Cells; Carboxylic Acids; Carcinogenesis; Dermatitis, Phototoxic; MCF-7 Cells
PubMed: 37687177
DOI: 10.3390/molecules28176347 -
Clinics in Dermatology 1998
Review
Topics: Dermatitis, Phototoxic; Diagnosis, Differential; Humans; Porphyrias
PubMed: 9554238
DOI: 10.1016/s0738-081x(97)00205-8 -
Turkish Journal of Pharmaceutical... Feb 2022Tattooing is an ancient practice and its popularity has been increasing in the recent years. After tattooing, complications may occur related to compose tattoo inks. In...
OBJECTIVES
Tattooing is an ancient practice and its popularity has been increasing in the recent years. After tattooing, complications may occur related to compose tattoo inks. In this study, the phototoxicity potential of the blue, red and black colors of the most commonly used three different commercially-available tattoo ink brands have been examined by performing 3T3-neutral red uptake (NRU) phototoxicity test.
MATERIALS AND METHODS
In the study, the phototoxicity of serial diluted concentrations of tattoo inks were evaluated with 3T3-NRU phototoxicity test method according to OECD guide 432. The data obtained from the NRU test result were uploaded to Phototox software (version 2.0) and the phototoxicity potentials of tattoo inks were determined via the calculation of the mean photo effect (MPE) and photo irritation factor (PIF) values.
RESULTS
The red, black and blue colors of three different commercially available tattoo inks did not cause a cytotoxic activity on BALB/c 3T3 cells with 3T3-NRU test. The IC values could not be determined +ultraviolet (UV) and -UV conditions. PIF values could not be calculated and MPE values were <0.1, which predicts the absence of phototoxic effect for all of the tested tattoo inks.
CONCLUSION
All tested inks were evaluated as non-phototoxic according to the results of MPE values calculated using Phototox software. However, test results should be verified by other phototoxicity test methods to obtain a comprehensive evaluation of phototoxic complications of different tattoo inks.
PubMed: 35227052
DOI: 10.4274/tjps.galenos.2021.86344 -
Scientific Reports Mar 2022Rucaparib (RCP) is a potent selective inhibitor of both PARP-1 and PARP-2 enzymes that induces synthetic lethality in cancer cells. It is used for the treatment of...
Rucaparib (RCP) is a potent selective inhibitor of both PARP-1 and PARP-2 enzymes that induces synthetic lethality in cancer cells. It is used for the treatment of breast and ovarian tumors harboring deleterious germline or somatic cancer susceptibility genes mutations. Although RCP has an indole chromophore in its structure, it displays a bathochromic shift of the absorption band towards the UVA region of sunlight, thus extending the active fraction of solar light able to produce photosensitivity reactions. In this context, it is highly interesting to study the photo(geno)toxicity disorders associated with this drug, bearing in mind that, for dermatologists it is crucial to understand the toxicity mechanism to improve clinical management. In the present work, RCP has shown to be potentially phototoxic, as observed in the neutral red uptake phototoxicity test. Moreover, this significant phototoxicity is attributed to both proteins and genomic DNA, as revealed in the protein photooxidation and comet assays. The results obtained are highly relevant concerning RCP photosafety and become clinically important in the context of identification of the cutaneous adverse events that can be associated with the targeted therapies. Interestingly, this is the first example of a PARP inhibitor able to induce photosensitized damage to biomolecules.
Topics: Antineoplastic Agents; Comet Assay; Dermatitis, Phototoxic; Humans; Indoles; Poly(ADP-ribose) Polymerase Inhibitors
PubMed: 35236893
DOI: 10.1038/s41598-022-07319-9 -
The British Journal of Ophthalmology Dec 2000To assess the retinal phototoxicity hazards of and to provide safety margins for endoillumination during vitrectomy.
AIM
To assess the retinal phototoxicity hazards of and to provide safety margins for endoillumination during vitrectomy.
METHODS
The absolute power and spectral distribution from various light sources and filter combinations that are commercially available for vitreous surgery were measured. The maximal exposure times based on the ICNIRP safety guidelines for photochemical and thermal injury of the aphakic eye were calculated. Additionally, the effect of various measures that reduce the risk of phototoxicity was evaluated.
RESULTS
Measurements of the spectrum and energy indicated that the ICNIRP safety guidelines for photochemical retinal damage are exceeded within 1 minute for nine out of 10 combinations tested. With an additional 475 nm long pass filter, light levels below 10 mW, and a distance from light probe to retina of at least 10 mm, the allowable exposure time can be increased up to 13 minutes. Thermal damage can be anticipated when the light probe touches the retina.
CONCLUSION
Commercially available light sources for endoillumination during vitrectomy are not safe with respect to photochemical retinal damage. Even with maximal precautions macular phototoxic damage remains a factual danger during vitrectomy.
Topics: Hot Temperature; Humans; Intraoperative Period; Lighting; Practice Guidelines as Topic; Radiation Dosage; Radiation Injuries; Retina; Vitrectomy
PubMed: 11090475
DOI: 10.1136/bjo.84.12.1372