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Toxicology Letters Dec 1998We examined the mechanisms of quinolone phototoxicity in vivo and in vitro. Simultaneous p.o. administration of a quinolone and ultraviolet-A (UVA) irradiation for 4 h... (Review)
Review
We examined the mechanisms of quinolone phototoxicity in vivo and in vitro. Simultaneous p.o. administration of a quinolone and ultraviolet-A (UVA) irradiation for 4 h induced auricular skin inflammation in BALB/c mice, including edema and neutrophil infiltration in the dermis. Antioxidants inhibited the inflammation in the early stage and cyclooxygenase inhibitors did in both the early and later stages, whereas 5-lipoxygenase inhibitors or histamine antagonists had no effect. The phototoxic inflammation was also induced in mast cell-deficient WBB6F1-W/Wv mice. Corresponding to the in vivo results, incubation with a quinolone under UVA irradiation stimulated BALB/c 3T3 mouse fibroblast cells to release prostaglandin E2 (PGE2) and 6-keto-PGF1alpha, but not leukotriene B4. In contrast, UVA-pre-irradiated quinolones did not affect PG release from fibroblasts. The PGE2 release was inhibited by cyclooxygenase inhibitors, antioxidants, protein kinase C (PKC) inhibitors and a tyrosine kinase (TK) inhibitor, but not by antibodies against tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1). These results lead to a hypothesis that reactive oxygen species generated from quinolones under UVA irradiation trigger PG release from dermal fibroblasts via PKC and TK activation, resulting in skin inflammation and that 5-lipoxygenase products, histamine, TNF alpha or IL-1 is ruled out from the mechanism.
Topics: 3T3 Cells; Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Dermatitis, Phototoxic; Dinoprostone; Fluoroquinolones; Mice; Mice, Inbred BALB C; Ultraviolet Rays
PubMed: 10022281
DOI: 10.1016/s0378-4274(98)00234-3 -
Annales de Dermatologie Et de... 2009
Topics: Adult; Amoxicillin; Anti-Bacterial Agents; Dermatitis, Phototoxic; Humans; Male
PubMed: 19560618
DOI: 10.1016/j.annder.2009.04.001 -
Current Drug Safety May 2009Drug-induced photoirritation can be defined as an inflammatory reaction of the skin after topical or systemic administration of pharmaceutical substances. In many cases... (Review)
Review
Drug-induced photoirritation can be defined as an inflammatory reaction of the skin after topical or systemic administration of pharmaceutical substances. In many cases of drug-induced phototoxicity, skin reactions can be triggered by doses of sunlight regarded as harmless and most often in the ultraviolet A (320-400 nm). Several classes of drugs including antibacterials, thiazide diuretics, non-steroidal anti-inflammatory drugs, quinolones, and tricyclic antidepressants, even though nontoxic by themselves, may become reactive under exposure to environmental light, leading to undesired side effects. At least three types of drug-induced phototoxic skin reactions, including the photoirritant, photogenotoxic and photoallergic skin responses, have been recognized, and their mechanisms and pathologic features are quite different. The development of effective methodology to evaluate the photochemical/biological properties has been attempted over the past few years, since it would be a key consideration to predict and avoid the phototoxic risk in the early phase of the drug discovery process. The aim of this review is to describe the clinical features, pathogenesis and photochemical characteristics of drug-induced phototoxicity, and the current developments in research tools for predicting phototoxic potential of new drug entities are also addressed.
Topics: Dermatitis, Photoallergic; Dermatitis, Phototoxic; Drug Discovery; Drug-Related Side Effects and Adverse Reactions; Humans; Light; Risk Assessment; Ultraviolet Rays
PubMed: 19442106
DOI: 10.2174/157488609788173044 -
The Journal of Emergency Medicine Mar 2014
Topics: Adult; Antifungal Agents; Dermatitis, Phototoxic; Drug Eruptions; Female; Foot Dermatoses; Humans; Pyrimidines; Skin Diseases, Vesiculobullous; Sunbathing; Triazoles; Voriconazole
PubMed: 24412056
DOI: 10.1016/j.jemermed.2013.09.018 -
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 -
Skinmed 2011Phototoxicity can be either harmful and induce adverse skin reactions or beneficial and be used therapeutically as in psoralen and UV-A or photodynamic therapy. Hundreds... (Review)
Review
Phototoxicity can be either harmful and induce adverse skin reactions or beneficial and be used therapeutically as in psoralen and UV-A or photodynamic therapy. Hundreds of medicinal plants are widely used in Asia and Western countries in oriental medicine, yet the phototoxicity of oriental medicinal plants is an understudied area. In this contribution, the authors discuss some methods used to measure the phototoxicity of plants and give an overview of the results of their previous and ongoing studies into the phototoxicity of medicinal plants. The authors argue that because they found that more than a quarter of oriental medicinal plants can be phototoxic, such research is helpful for dermatologists and that active phototoxic components extracted from oriental medicinal plants may be used therapeutically.
Topics: Animals; Dermatitis, Phototoxic; Humans; Medicine, East Asian Traditional; Photochemotherapy; Photosensitizing Agents; Plant Extracts; Plants, Medicinal
PubMed: 22165044
DOI: No ID Found -
The Journal of Pediatrics Jan 2024
Topics: Humans; Pastinaca; Dermatitis, Phototoxic
PubMed: 37696389
DOI: 10.1016/j.jpeds.2023.113727 -
International Journal of Infectious... Sep 2015
Topics: Adult; Citrus; Dermatitis, Phototoxic; Diagnosis, Differential; Female; Fruit and Vegetable Juices; Humans
PubMed: 26166698
DOI: 10.1016/j.ijid.2015.07.004 -
The Pediatric Infectious Disease Journal Jul 2012Voriconazole is used in antifungal prophylaxis. We performed a retrospective review of immunocompromised children receiving prophylaxis with voriconazole during major...
Voriconazole is used in antifungal prophylaxis. We performed a retrospective review of immunocompromised children receiving prophylaxis with voriconazole during major hospital renovation, who developed phototoxic skin reactions. The overall incidence of phototoxic skin reactions was 33%. A voriconazole dose of ≥6 mg/kg of body weight per dose twice daily was associated with a significantly greater risk to develop phototoxic skin reactions compared with lower doses.
Topics: Chemoprevention; Child; Child, Preschool; Dermatitis, Phototoxic; Female; Humans; Immunocompromised Host; Incidence; Infant; Male; Mycoses; Neoplasms; Pyrimidines; Retrospective Studies; Risk Assessment; Triazoles; Voriconazole
PubMed: 22517339
DOI: 10.1097/INF.0b013e3182566311 -
Regulatory Toxicology and Pharmacology... Nov 2022Phototoxicity testing is required by European regulations for agrochemicals with UV/visible molar extinction/absorption coefficient (MEC) higher than 10 L x mol x cm in...
Phototoxicity testing is required by European regulations for agrochemicals with UV/visible molar extinction/absorption coefficient (MEC) higher than 10 L x mol x cm in the 290-700 nm wavelength range. Furthermore, regulations identify a need of considering human exposure in case of positive results. While in vitro OECD test guidelines are available for hazard characterisation, there is no guidance on how to utilise positive results in human exposure risk assessments. Our goal was to take a first step towards developing a NAM based tiered testing approach and a framework for non-dietary acute human dermal risk assessment for phototoxicity to agrochemicals. The proposed framework can be divided into a few steps: 1) use the OECD updated MEC values of 1000 L x mol x cm as trigger for phototoxicity testing; 2) establish a reference concentration (RfC) from in vitro phototoxicity studies using BMC approach, 3) estimate potential exposure to skin, target organ for phototoxicity, using EFSA exposure models, product specific labels and skin penetration values, and 4) phototoxicity risk assessment; 5) refinement to RfC and/or exposure estimates can be considered. Finally, case studies of a nematicide and an herbicide active substance are provided to illustrate the proposed framework.
Topics: Agrochemicals; Dermatitis, Phototoxic; Herbicides; Humans; Risk Assessment; Skin
PubMed: 36007800
DOI: 10.1016/j.yrtph.2022.105250