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The Journal of Investigative Dermatology Sep 1993Doxycycline (DOTC) is a photosensitizing drug whose mechanism of phototoxicity is complicated by the large variety of stable photoproducts formed. To assess the role of...
Doxycycline (DOTC) is a photosensitizing drug whose mechanism of phototoxicity is complicated by the large variety of stable photoproducts formed. To assess the role of a DOTC photoproduct, lumidoxycycline (LuDOTC), in the photosensitization mechanism of DOTC, MGH-U1 human bladder carcinoma cells were treated in vitro with either DOTC or LuDOTC, and irradiated with the 351-nm emission of an argon-ion laser. Both DOTC and LuDOTC were phototoxic and caused radiant-exposure-dependent inhibition of cellular incorporation of tritiated thymidine. On an absorbed-photon basis, DOTC was about five times as phototoxic as LuDOTC. Cellular uptake of DOTC was about five times as great as that of LuDOTC. Epifluorescence microscopy showed localization of LuDOTC predominantly within cellular membranes, particularly of mitochondria, as well as a low level of LuDOTC fluorescence diffusely within the cytoplasm. Epifluorescence microscopy of cells labeled with the mitochondrial probe, rhodamine 123, showed mitochondrial fragmentation and altered mitochondrial membrane integrity after LuDOTC photosensitization; these effects depended on radiant exposure and were partially reversible by 24 h after irradiation. For both DOTC and LuDOTC, phototoxicity was increased by irradiation in the presence of deuterium oxide and decreased in the presence of sodium azide, effects consistent with an important mechanistic role for singlet oxygen, O2(1 delta g), in the injury. In solution, LuDOTC and DOTC had similar quantum yields for generation of O2(1 delta g) as measured by time-resolved spectroscopy and by O2(1 delta g) trapping. LuDOTC was photostable in solution, but DOTC underwent significant photodegradation. These data demonstrate that DOTC photo-products such as LuDOTC have significant photobiologic activity and may play an important role in the phototoxicity mechanism of DOTC.
Topics: Doxycycline; Humans; Intracellular Fluid; Lasers; Nitrogen; Photochemistry; Photosensitivity Disorders; Photosensitizing Agents; Tumor Cells, Cultured; Water
PubMed: 8370969
DOI: 10.1111/1523-1747.ep12365484 -
Toxicology Research Nov 2018Phototoxicity can cause toxic responses such as edemas and lesions, and is one of the severe adverse effects that largely limit the use of these phototoxic drugs. Some... (Review)
Review
Phototoxicity can cause toxic responses such as edemas and lesions, and is one of the severe adverse effects that largely limit the use of these phototoxic drugs. Some traditional Chinese medicines (TCMs) and their constituents have been reported to be phototoxic. However, to date, their phototoxicity information is still very limited, and lacks systemic investigation. This article presents the phototoxicity potential of various types of TCMs and their active components in an effort to provide valuable information for drug research and discovery to mitigate phototoxicity concerns. Some potential mechanisms of action (MoAs) of phototoxicity are discussed. In addition, and phototoxicity assays are summarized this review.
PubMed: 30542599
DOI: 10.1039/c8tx00141c -
ACS Nano Jun 2023Intratumoral pathogens can contribute to cancer progression and affect therapeutic response. , a core pathogen of colorectal cancer (CRC), is an important cause of low...
Intratumoral pathogens can contribute to cancer progression and affect therapeutic response. , a core pathogen of colorectal cancer (CRC), is an important cause of low therapeutic efficacy and metastasis. Thus, the modulation of intratumoral pathogens may provide a target for cancer therapy and metastasis inhibition. Herein, we propose an intratumoral -modulating strategy for enhancing the therapeutic efficacy of CRC and inhibiting lung metastasis by designing an antibacterial nanoplatform (Au@BSA-CuPpIX), which produced reactive oxygen species (ROS) under ultrasound and exhibited strong antibacterial activity. Importantly, Au@BSA-CuPpIX reduced the levels of apoptosis-inhibiting proteins by inhibiting intratumoral , thereby enhancing ROS-induced apoptosis. results demonstrated that Au@BSA-CuPpIX effectively eliminated to enhance the therapeutic efficacy of sonodynamic therapy (SDT) for orthotopic CRC and inhibit lung metastasis. Notably, entrapped gold nanoparticles reduced the phototoxicity of metalloporphyrin accumulated in the skin during tumor treatment, preventing severe inflammation and damage to the skin. Therefore, this study proposes a strategy for the elimination of in CRC to enhance the therapeutic effect of SDT, thus providing a promising paradigm for improving cancer treatment with fewer toxic side effects and promoting the clinical translational potential of SDT.
Topics: Humans; Fusobacterium nucleatum; Colorectal Neoplasms; Gold; Reactive Oxygen Species; Metal Nanoparticles
PubMed: 37201179
DOI: 10.1021/acsnano.3c01308 -
Deutsches Arzteblatt International Mar 2020
Topics: Antimalarials; Dermatitis, Phototoxic; Doxycycline; Female; Humans; Young Adult
PubMed: 32343652
DOI: 10.3238/arztebl.2020.0196 -
Advances in Colloid and Interface... Dec 2015Cancer treatment using conventional drug delivery platforms may lead to fatal damage to normal cells. Among various intelligent delivery platforms, photoresponsive... (Review)
Review
Cancer treatment using conventional drug delivery platforms may lead to fatal damage to normal cells. Among various intelligent delivery platforms, photoresponsive delivery platforms are becoming popular, as light can be easily focused and tuned in terms of power intensity, wavelength, and irradiation time, allowing remote and precise control over therapeutic payload release both spatially and temporally. This unprecedented controlled delivery manner is important to improve therapeutic efficacy while minimizing side effects. However, most of the existing photoactive delivery platforms require UV/visible excitation to initiate their function, which suffers from phototoxicity and low level of tissue penetration limiting their practical applications in biomedicine. With the advanced optical property of converting near infrared (NIR) excitation to localized UV/visible emission, upconversion nanoparticles (UCNPs) have emerged as a promising photoactive delivery platform that provides practical applications for remote spatially and temporally controlled release of therapeutic payload molecules using low phototoxic and high tissue penetration NIR light as the excitation source. This article reviews the state-of-the-art design, synthesis and therapeutic molecular payload encapsulation strategies of UCNP-based photoactive delivery platforms for cancer therapy. Challenges and promises for engineering of advanced delivery platforms are also highlighted.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; DNA; Drug Delivery Systems; Humans; Infrared Rays; Neoplasms; Photochemotherapy; RNA, Small Interfering
PubMed: 26520243
DOI: 10.1016/j.cis.2015.10.003 -
Redox Biology 2014Reactive Oxygen Species (ROS) are known to cause oxidative damage to DNA, proteins and lipids. In addition, recent evidence suggests that ROS can also initiate signaling... (Review)
Review
Reactive Oxygen Species (ROS) are known to cause oxidative damage to DNA, proteins and lipids. In addition, recent evidence suggests that ROS can also initiate signaling cascades that respond to stress and modify specific redox-sensitive moieties as a regulatory mechanism. This suggests that ROS are physiologically-relevant signaling molecules. However, these sensor/effector molecules are not uniformly distributed throughout the cell. Moreover, localized ROS damage may elicit site-specific compensatory measures. Thus, the impact of ROS can be likened to that of calcium, a ubiquitous second messenger, leading to the prediction that their effects are exquisitely dependent upon their location, quantity and even the timing of generation. Despite this prediction, ROS signaling is most commonly intuited through the global administration of chemicals that produce ROS or by ROS quenching through global application of antioxidants. Optogenetics, which uses light to control the activity of genetically-encoded effector proteins, provides a means of circumventing this limitation. Photo-inducible genetically-encoded ROS-generating proteins (RGPs) were originally employed for their phototoxic effects and cell ablation. However, reducing irradiance and/or fluence can achieve sub-lethal levels of ROS that may mediate subtle signaling effects. Hence, transgenic expression of RGPs as fusions to native proteins gives researchers a new tool to exert spatial and temporal control over ROS production. This review will focus on the new frontier defined by the experimental use of RGPs to study ROS signaling.
Topics: Animals; Antioxidants; Green Fluorescent Proteins; Optogenetics; Photochemotherapy; Reactive Oxygen Species
PubMed: 24563855
DOI: 10.1016/j.redox.2014.01.019 -
Wideochirurgia I Inne Techniki... Jun 2022Erythropoietic protoporphyria is a hereditary defect in heme synthesis, causing protoporphyrin deposition and phototoxic reactions after exposure to light, especially at...
Erythropoietic protoporphyria is a hereditary defect in heme synthesis, causing protoporphyrin deposition and phototoxic reactions after exposure to light, especially at a wavelength of about 400 nm. Sensitivity to light may cause postoperative complications. Therefore, in open surgery protective filters are employed on surgical luminaires. The dangers of laparoscopy are little understood and the intensity of the light used can be high. To protect against phototoxic injury, we inserted an OG 530 filter in the video track. This filter blocks wavelengths below 470 nm. Three cholecystectomies and one sigmoidectomies were performed laparoscopically. The procedures were uneventful, and the patients suffered no adverse reactions, including phototoxic symptoms. The filter had a moderate influence on color perception and caused no significant restrictions on working conditions. We consider that it is appropriate to develop a relevant design to meet the suitable requirements for a durable filter holder in the laparoscopic video track.
PubMed: 35707342
DOI: 10.5114/wiitm.2022.115003 -
Molecules (Basel, Switzerland) Dec 2021Polyphenols are a large family of natural compounds widely used in cosmetic products due to their antioxidant and anti-inflammatory beneficial properties and their...
Polyphenols are a large family of natural compounds widely used in cosmetic products due to their antioxidant and anti-inflammatory beneficial properties and their ability to prevent UV radiation-induced oxidative stress. Since these compounds present chromophores and are applied directly to the skin, they can react with sunlight and exert phototoxic effects. The available scientific information on the phototoxic potential of these natural compounds is scarce, and thus the aim of this study was to evaluate the photoreactivity and phototoxicity of five phenolic antioxidants with documented use in cosmetic products. A standard ROS assay was validated and applied to screen the photoreactivity of the natural phenolic antioxidants caffeic acid, ferulic acid, -coumaric acid, 3,4-dihydroxyphenylacetic acid (DOPAC), and rutin. The phototoxicity potential was determined by using a human keratinocyte cell line (HaCaT), based on the 3T3 Neutral Red Uptake phototoxicity test. Although all studied phenolic antioxidants absorbed UV/Vis radiation in the range of 290 to 700 nm, only DOPAC was able to generate singlet oxygen. The generation of reactive oxygen species is an early-stage chemical reaction as part of the phototoxicity mechanism. Yet, none of the studied compounds decreased the viability of keratinocytes after irradiation, leading to the conclusion that they do not have phototoxic potential. The data obtained with this work suggests that these compounds are safe when incorporated in cosmetic products.
Topics: Animals; Antioxidants; Biological Assay; Biological Products; Cell Line; Cell Survival; Dermatitis, Phototoxic; Humans; Mice; Molecular Structure; Polyphenols; Reactive Oxygen Species
PubMed: 35011420
DOI: 10.3390/molecules27010189 -
The Study on Timolol and Its Potential Phototoxicity Using Chemical, In Silico and In Vitro Methods.Pharmaceuticals (Basel, Switzerland) Jan 2024Timolol (TIM) is a non-selective ß-adrenergic receptor antagonist used orally for the treatment of hypertension and heart attacks, and topically for treating glaucoma;...
Timolol (TIM) is a non-selective ß-adrenergic receptor antagonist used orally for the treatment of hypertension and heart attacks, and topically for treating glaucoma; lately, it has also been used in some specific dermatological problems. In the present study, its photodegradation and potential risk of phototoxicity were examined using chemical, in silico and in vitro methods. The UV/VIS irradiated solutions of TIM at pH 1-13 were subjected to LC-UV and UPLC-HRMS/MS analyses showing pseudo first-order kinetics of degradation and several degradation products. The structures of these photodegradants were elucidated by fragmentation path analysis based on high resolution (HR) fragmentation mass spectra, and then used for toxicity evaluation using OSIRIS Property Explorer and Toxtree. Potential risk of phototoxicity was also studied using chemical tests for detecting ROS under UV/VIS irradiation and in vitro tests on BALB/c 3T3 mouse fibroblasts (MTT, NRU and Live/Dead tests). TIM was shown to be potentially phototoxic because of its UV/VIS absorptive properties and generation ROS during irradiation. As was observed in the MTT and NRU tests, the co-treatment of fibroblasts with TIM and UV/VIS light inhibited cell viability, especially when concentrations of the drug were higher than 50 µg/mL.
PubMed: 38256931
DOI: 10.3390/ph17010098 -
Actas Dermo-sifiliograficas May 2014Thiazides are widely used diuretics that first became available in the 1950s. The first reports of photosensitivity reactions to thiazides were published shortly after... (Review)
Review
Thiazides are widely used diuretics that first became available in the 1950s. The first reports of photosensitivity reactions to thiazides were published shortly after the introduction of these drugs, but few cases have been described since. We review all the cases of photosensitivity due to thiazides published up to December 2011. We found 62 cases, 33 in women and 29 in men. The most common presentation was eczematous lesions in a photodistributed pattern, and the most common causative agent was hydrochlorothiazide. The results of photobiological studies were published in only some of the cases reviewed. In most cases, phototesting revealed an abnormal response to UV-A alone or to both UV-A and UV-B. In some cases, the results of phototesting were normal and only photopatch testing yielded abnormal results. Diagnosis of photosensitivity due to thiazides requires a high degree of suspicion. Ideally, diagnosis should be confirmed by a photobiological study.
Topics: Dermatitis, Phototoxic; Female; Humans; Male; Thiazides
PubMed: 23664250
DOI: 10.1016/j.ad.2013.01.010