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Photodermatology, Photoimmunology &... Apr 2002Potential phototoxicity has been described for a number of drugs and chemical substances. Psoralens, chlorpromazines and fluoroquinolones have been described as inducing...
Phototoxicity to diuretics and antidiabetics in the cultured keratinocyte cell line HaCaT: evaluation by clonogenic assay and single cell gel electrophoresis Comet assay).
BACKGROUND
Potential phototoxicity has been described for a number of drugs and chemical substances. Psoralens, chlorpromazines and fluoroquinolones have been described as inducing photomutagenicity and photocarcinogenicity in vitro and in vivo. We wanted to investigate oral antidiabetics and diuretics for potential phototoxicity and possible DNA damage in the HaCaT cell line.
METHODS
: The oral antidiabetics tolbutamide, glibenclamide and glipizide, and the diuretics bendroflumethiazide, butizide, furosemide, hydrochlorothiazide and trichlormethiazide were dissolved in DMSO to final concentrations of 1 mM, 0.1 mM, and 0.01 mM, incubated together with the cells, and exposed to UVA1 (23 or 48 J/cm2). Cell survival was evaluated in a clonogenic assay and phototoxic DNA damage was investigated by single cell gel electrophoresis (comet assay). To investigate possible inhibiting effects of antioxidants, L-ascorbic acid and alpha-tocopherol were added at a final concentration of 1 mM 24 h before treatment with the drugs.
RESULTS
Bendroflumethiazide, furosemide, hydrochlorothiazide, trichlormethiazide and tolbutamide induced dose-dependent phototoxicity in the clonogenic assay. Cells incubated with bendroflumethiazide, tolbutamide and glibenclamide and irradiated with UVA1 demonstrated increased oxidative DNA damage, revealed as alkali-labile sites in the comet assay. Pretreatment with L-ascorbic acid or alpha-tocopherol suppressed the UVA-induced DNA damage in cells incubated with 1 mM bendroflumethiazide, furosemide, glibenclamide, glipizide, tolbutamide or trichloromethiazide.
CONCLUSION
Several oral antidiabetics and diuretics show phototoxic effects in the HaCaT cell line. Inhibiting effects of antioxidants point towards involvement of reactive oxygen species in phototoxic DNA damage, suggesting a link between the phototoxic and photocancerogenic potential of the sulfonamide-derived oral antidiabetic and diuretic drugs. Excessive exposure to UV light may be deleterious for patients treated with oral antidiabetic and diuretic drugs.
Topics: Cell Death; Cell Line; DNA Damage; Dermatitis, Phototoxic; Diuretics; Hypoglycemic Agents; Keratinocytes; Ultraviolet Rays
PubMed: 12147042
DOI: 10.1034/j.1600-0781.2002.180206.x -
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 -
International Journal of Pharmaceutics Feb 2016The purpose of this study was to examine skin irritation and phototoxicity potentials of several microemulsions (ME), all comprising approximately the same percentage of... (Comparative Study)
Comparative Study
The purpose of this study was to examine skin irritation and phototoxicity potentials of several microemulsions (ME), all comprising approximately the same percentage of surfactant mixture, but varying oil/water content and consequently inner structure being either droplet-like (o/w ME, o/w ME carbomer, w/o ME and w/o ME white wax) or lamellar (gel-like ME). Two different in vitro methods were used: MTT assay (performed either on reconstructed human epidermis (RHE) or NCTC 2544 cells) and pig ear test. Neither assay revealed the difference among ME with droplet-like structure. Then again, pig ear test and MTT assay performed on RHE indicated that gel-like ME is more irritant compared to other tested ME, whereas no difference among formulations were observed by MTT assay on NCTC 2544 cells. The reasonable explanation is destruction and consequently uniform structure of ME upon dilution that is inevitable for testing on cell cultures. The results of phototoxicity test again indicated the increased potential of gel-like ME to cause adverse effects on skin. It can be concluded that for ME consisting of the same amount of identical surfactants but having different structure the latter represent a crucial factor that determines their dermal toxicity.
Topics: Animals; Cell Line; Chemistry, Pharmaceutical; Dermatitis, Phototoxic; Emulsions; Humans; Keratinocytes; Skin; Skin Irritancy Tests; Surface-Active Agents; Swine
PubMed: 26757147
DOI: 10.1016/j.ijpharm.2015.12.064 -
Journal of Medicinal Chemistry Jul 2023Phototoxicity is a common safety concern encountered by project teams in pharmaceutical research and has the potential to stop progression of an otherwise promising... (Review)
Review
Phototoxicity is a common safety concern encountered by project teams in pharmaceutical research and has the potential to stop progression of an otherwise promising candidate molecule. This perspective aims to provide an overview of the approaches toward mitigation of phototoxicity that medicinal chemists have taken during the lead optimization phase in the context of regulatory standards for photosafety evaluation. Various strategies are laid out based on available literature examples in order to highlight how structural modification can be utilized toward successful mitigation of a phototoxicity liability. A proposed flowchart is presented as a guidance tool to be used by the practicing medicinal chemist when facing a phototoxicity risk. The description of available tools to consider in the drug design process will include an overview of the evolution of in silico methods and their application as well as structure alerts for consideration as potential phototoxicophores.
Topics: Humans; Drug Discovery; Drug Design; Dermatitis, Phototoxic; Chemistry, Pharmaceutical
PubMed: 37450689
DOI: 10.1021/acs.jmedchem.3c00749 -
Acta Clinica Croatica Jun 2017When taking different drugs, their possible side effects on the skin should be considered, including skin reactions connected to photosensitivity. This photosensitivity... (Review)
Review
When taking different drugs, their possible side effects on the skin should be considered, including skin reactions connected to photosensitivity. This photosensitivity caused by drugs can appear as phototoxic reactions (which occur more often) or photoallergic reactions (which occur less often and include allergic mechanisms). The following drugs stand out as medications with a high photosensitivity potential: nonsteroidal anti-inflammatory drugs (NSAIDs), cardiovascular drugs (such as amiodarone), phenothiazines (especially chlorpromazine), retinoids, antibiotics (sulfonamides, tetracyclines, especially demeclocycline and quinolones), etc. In recent years, photosensitive reactions to newer drugs have appeared, e.g., targeted anticancer therapies such as BRAF kinase inhibitors (vemurafenib, dabrafenib), EGFR inhibitors, VEGFR inhibitors, MEK inhibitors, Bcr-Abl tyrosine kinase inhibitors, etc. In patients taking drugs over a longer period of time (e.g., NSAIDs, cardiovascular drugs, etc.), a particular problem arises when an unrecognized drug-induced photosensitivity on the skin manifests in summer months. When taking patient histories, the physician/dermatovenereologist should bear in mind that any drug the patient is currently taking may be the cause of skin reactions. Therefore, patients who use potentially photosensitive drugs and treatments on a long term basis should be warned of the possibility of these side effects on their skin and advised to avoid direct exposure to sunlight and to use adequate photoprotection. If patients carefully protect themselves from the sun, it is often not necessary to stop treatments that include photosensitive drugs. If such reactions appear, anti-inflammatory and antiallergic therapies should be introduced.
Topics: Dermatitis, Photoallergic; Dermatitis, Phototoxic; Diagnosis, Differential; Drug-Related Side Effects and Adverse Reactions; Humans; Photosensitivity Disorders; Sunlight
PubMed: 29485795
DOI: 10.20471/acc.2017.56.02.11 -
PloS One 2018Many chemicals have been reported to induce phototoxicity. The absorbance of light energy within the sunlight range is a common characteristic of phototoxicity. The 3T3...
Exploration of alternative test methods to evaluate phototoxicity of ophthalmic agents by using Statens Seruminstitut Rabbit Cornea cell lines and 3D human reconstituted cornea models.
Many chemicals have been reported to induce phototoxicity. The absorbance of light energy within the sunlight range is a common characteristic of phototoxicity. The 3T3 NRU phototoxicity test (PT) in 3T3 mouse skin fibroblasts has been used to identify the phototoxic potential induced by excited chemicals after exposure to ultra violet (UV). However, as phototoxicity may occur in ocular cells, it is necessary to develop a more suitable test for cornea-derived cells. In this study, we attempted to establish a new in vitro PT method in rabbit corneal cell lines (SIRC). We evaluated five ophthalmic agents, ciprofloxacin, levofloxacin, lomefloxacin, norfloxacin, and tetracycline, for their cytotoxic potential and in vitro phototoxicity. The results obtained using 3D human corneal models revealed that the UV-induced eye tissue toxicity by the test substances showed good correlation with those obtained using the in vitro phototoxicity test. However, the results from the 3D PT for ciprofloxacin, norfloxacin, and tetracycline in the 3D human cornea model were only partially comparable. Therefore, we suggest the SIRC cell line as a new phototoxicity test model; however, a sequential testing strategy, such as 3D PT, was also proposed to obtain relevant information for topical eye agents.
Topics: 3T3 Cells; Animals; Biological Assay; Cell Line; Cornea; Dermatitis, Phototoxic; Fibroblasts; Humans; Mice; Ophthalmic Solutions; Rabbits; Ultraviolet Rays
PubMed: 29782497
DOI: 10.1371/journal.pone.0196735 -
Medicina (Kaunas, Lithuania) 2006Photosensitive skin reactions occur when human skin reacts to ultraviolet radiation or visible light abnormally. The forms of photosensitivity are phototoxicity and... (Comparative Study)
Comparative Study Review
Photosensitive skin reactions occur when human skin reacts to ultraviolet radiation or visible light abnormally. The forms of photosensitivity are phototoxicity and photoallergy. Phototoxic disorders have a high incidence, whereas photoallergic reactions are much less frequent in human population. Several hundred substances, chemicals, or drugs may invoke phototoxic and photoallergic reactions. In order to avoid photosensitive reactions it is essential to determine the photosensitizing properties of such substances before drugs are introduced in therapy or products made available on the market. The article reviews the mechanisms of photosensitization, explains the most important differences between phototoxic and photoallergic reactions, summarizes the most common photosensitizers, and presents the clinical features and diagnostic procedures of phototoxic and photoallergic reactions.
Topics: Adult; Child; Dermatitis, Photoallergic; Dermatitis, Phototoxic; Diagnosis, Differential; Drug-Related Side Effects and Adverse Reactions; Humans; Photosensitivity Disorders; Skin Tests; Sunburn; Sunscreening Agents
PubMed: 16963827
DOI: No ID Found -
Romanian Journal of Morphology and... 2014Vision is based on the sensitivity of the eye to visible rays of the solar spectrum, which allows the recording and transfer of visual information by photoelectric... (Review)
Review
Vision is based on the sensitivity of the eye to visible rays of the solar spectrum, which allows the recording and transfer of visual information by photoelectric reaction. Any electromagnetic radiation, if sufficiently intense, may cause damages in living tissues. In a changing environment, the aim of this paper is to point out the impact of light radiation on ocular cells, with its phototoxicity potential on eye tissues. In fact, faced with light and oxygen, the eye behaves like an ephemeral aggregate of unstable molecules, like a temporary crystallization threatened with entropia.
Topics: Cornea; Dermatitis, Phototoxic; Electromagnetic Radiation; Eye; Humans; Lens, Crystalline; Light; Ultraviolet Rays; Vision, Ocular
PubMed: 24969972
DOI: No ID Found -
Drugs 1995The main types of adverse effects associated with quinolones are uncommon and reversible and vary in frequency among different agents. Phototoxicity appears more... (Review)
Review
The main types of adverse effects associated with quinolones are uncommon and reversible and vary in frequency among different agents. Phototoxicity appears more frequent with lomefloxacin than with some other quinolones. Three mechanisms have been proposed to explain the neurotoxic effects, including rare proconvulsant activity, associated with quinolone therapy. Arthropathy remains a dilemma for paediatricians deciding whether to use quinolones in growing children. Importantly, the experience with temafloxacin, which has now been withdrawn from the market, emphasises the need for thorough postmarketing surveillance. Nonetheless, it should be remembered that the fluoroquinolones as a group are effective and very well tolerated antimicrobial drugs.
Topics: Anti-Infective Agents; Dermatitis, Phototoxic; Fluoroquinolones; Humans; Joint Diseases; Nervous System Diseases; Quinolones
PubMed: 8549287
DOI: 10.2165/00003495-199500492-00026 -
Photodermatology, Photoimmunology &... 2007Exposure to ultraviolet radiation (UVR) has been shown to induce cutaneous biological changes and phototoxic reactions.
BACKGROUND
Exposure to ultraviolet radiation (UVR) has been shown to induce cutaneous biological changes and phototoxic reactions.
OBJECTIVE
This study was designed to evaluate the usefulness of artificial skin (AS) composed of keratinocytes and melanocytes as an in vitro phototoxicity model for topical agents.
MATERIALS AND METHODS
AS was manufactured with three-dimensionally cultured keratinocytes and melanocytes on a de-epidermized dermis (DED). The photobiological responses in AS with and without melanocytes were comparatively examined after ultraviolet A (UVA) exposure. Three test chemicals (8-methoxypsoralen, 6-methylcoumarin and tetracycline) were topically applied onto the AS with melanocytes and after UVA irradiation, the released inflammatory cytokines (IL-1alpha, IL-beta and IL-6) were analyzed.
RESULTS
AS with melanocytes showed better epidermal structures, stronger resistance to UVA exposure and photobiological responses closer to in vivo human skin. Releases of inflammatory cytokines were well correlated with the increased phototoxicities of test chemicals. Among the measured cytokines, IL-6 could be the most reliable in vitro marker indicative of phototoxic potential, because it showed statistically significant increase only in case of concurrent exposure to chemicals and UVA.
CONCLUSION
The AS with melanocytes may be a useful tool especially for examining UV-induced cutaneous changes and a promising in vitro phototoxicity test model for topical agents.
Topics: Administration, Cutaneous; Biomarkers; Cell Culture Techniques; Coumarins; Cytokines; Dermatitis, Phototoxic; Humans; Interleukin-6; Keratinocytes; Melanocytes; Methoxsalen; Skin, Artificial; Tetracycline; Ultraviolet Rays
PubMed: 17523928
DOI: 10.1111/j.1600-0781.2007.00279.x