Phototoxicity | |
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Other names | Photoirritation |
Effect of the common rue on skin in hot weather. | |
Specialty | Dermatology |
Phototoxicity, also called photoirritation, is a chemically induced skin irritation, requiring light, that does not involve the immune system. [1] It is a type of photosensitivity. [1] [2]
The skin response resembles an exaggerated sunburn. The involved chemical may enter into the skin by topical administration, or it may reach the skin via systemic circulation following ingestion or parenteral administration. The chemical needs to be "photoactive," which means that when it absorbs light, the absorbed energy produces molecular changes that cause toxicity. Many synthetic compounds, including drug substances like tetracyclines or fluoroquinolones, are known to cause these effects. Surface contact with some such chemicals causes photodermatitis, and many plants cause phytophotodermatitis. Light-induced toxicity is a common phenomenon in humans; however, it also occurs in other animals.
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A phototoxic substance is a chemical compound which becomes toxic when exposed to light.
Phototoxicity is a quantum chemical phenomenon. Phototoxins are molecules with a conjugated system, often an aromatic system. They have a low-lying excited state that can be reached by excitation with visible light photons. This state can undergo intersystem crossing with neighboring molecules in tissue, converting them to toxic free radicals. These rapidly attack nearby molecules, killing cells. A typical radical is singlet oxygen, produced from regular triplet oxygen. Because free radicals are highly reactive, the damage is limited to the body part illuminated.
3T3 Neutral Red Phototoxicity Test – An in vitro toxicological assessment test used to determine the cytotoxicity and photo(cyto)toxicity effect of a test article to murine fibroblasts in the presence or absence of UVA light.
"The 3T3 Neutral Red Uptake Phototoxicity Assay (3T3 NRU PT) can be utilized to identify the phototoxic effect of a test substance induced by the combination of test substance and light. The test compares the cytotoxic effect of a test substance when tested after the exposure, then tested in the absence of exposure to a non-cytotoxic dose of UVA/vis light. Cytotoxicity is expressed as a concentration-dependent reduction of the uptake of the vital dye - Neutral Red.
Substances that are phototoxic in vivo after systemic application and distribution to the skin, as well as compounds that could act as phototoxicants after topical application to the skin can be identified by the test. The reliability and relevance of the 3T3 NRU PT have been evaluated, and the test has been shown to be predictive when compared with acute phototoxicity effects in vivo in animals and humans." Taken with permission from
Several health authorities have issued related guidance documents, which need to be considered for drug development:
When performing microscopy on live samples, one needs to be aware that too high light dose can damage or kill the specimens and lead to experimental artefacts. This is particularly important in confocal and super-resolution microscopy. [7] [8]
Pharmacology is a branch of medicine, biology, and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous molecule which exerts a biochemical or physiological effect on the cell, tissue, organ, or organism. It is the science of drugs including their origin, composition, pharmacokinetics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function. If substances have medicinal properties, they are considered pharmaceuticals.
Tetracycline, sold under various brand names, is an oral antibiotic in the tetracyclines family of medications, used to treat a number of infections, including acne, cholera, brucellosis, plague, malaria, and syphilis.
Sunscreen, also known as sunblock or sun cream, is a photoprotective topical product for the skin that helps protect against sunburn and most importantly prevent skin cancer. Sunscreens come as lotions, sprays, gels, foams, sticks, powders and other topical products. Sunscreens are common supplements to clothing, particularly sunglasses, sunhats and special sun protective clothing, and other forms of photoprotection.
Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder or brown recluse spider.
Photodynamic therapy (PDT) is a form of phototherapy involving light and a photosensitizing chemical substance, used in conjunction with molecular oxygen to elicit cell death (phototoxicity).
An assay is an investigative (analytic) procedure in laboratory medicine, mining, pharmacology, environmental biology and molecular biology for qualitatively assessing or quantitatively measuring the presence, amount, or functional activity of a target entity. The measured entity is often called the analyte, the measurand, or the target of the assay. The analyte can be a drug, biochemical substance, chemical element or compound, or cell in an organism or organic sample. An assay usually aims to measure an analyte's intensive property and express it in the relevant measurement unit.
A fluorescence microscope is an optical microscope that uses fluorescence instead of, or in addition to, scattering, reflection, and attenuation or absorption, to study the properties of organic or inorganic substances. "Fluorescence microscope" refers to any microscope that uses fluorescence to generate an image, whether it is a simple set up like an epifluorescence microscope or a more complicated design such as a confocal microscope, which uses optical sectioning to get better resolution of the fluorescence image.
Photosensitivity is the amount to which an object reacts upon receiving photons, especially visible light. In medicine, the term is principally used for abnormal reactions of the skin, and two types are distinguished, photoallergy and phototoxicity. The photosensitive ganglion cells in the mammalian eye are a separate class of light-detecting cells from the photoreceptor cells that function in vision.
Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used together with other chemotherapy agents. Doxorubicin is given by injection into a vein.
Autofluorescence is the natural emission of light by biological structures such as mitochondria and lysosomes when they have absorbed light, and is used to distinguish the light originating from artificially added fluorescent markers (fluorophores).
Tetracyclines are a group of broad-spectrum antibiotic compounds that have a common basic structure and are either isolated directly from several species of Streptomyces bacteria or produced semi-synthetically from those isolated compounds. Tetracycline molecules comprise a linear fused tetracyclic nucleus to which a variety of functional groups are attached. Tetracyclines are named after their four ("tetra-") hydrocarbon rings ("-cycl-") derivation ("-ine"). They are defined as a subclass of polyketides, having an octahydrotetracene-2-carboxamide skeleton and are known as derivatives of polycyclic naphthacene carboxamide. While all tetracyclines have a common structure, they differ from each other by the presence of chloro, methyl, and hydroxyl groups. These modifications do not change their broad antibacterial activity, but do affect pharmacological properties such as half-life and binding to proteins in serum.
Immunotoxicology is the study of the toxicity of foreign substances called xenobiotics and their effects on the immune system. Some toxic agents that are known to alter the immune system include: industrial chemicals, heavy metals, agrochemicals, pharmaceuticals, drugs, ultraviolet radiation, air pollutants and some biological materials. The effects of these immunotoxic substances have been shown to alter both the innate and adaptive parts of the immune system. Consequences of xenobiotics affect the organ initially in contact. Some commonly seen problems that arise as a result of contact with immunotoxic substances are: immunosuppression, hypersensitivity, and autoimmunity. The toxin-induced immune dysfunction may also increase susceptibility to cancer.
Alitretinoin, or 9-cis-retinoic acid, is a form of vitamin A. It is also used in medicine as an antineoplastic (anti-cancer) agent developed by Ligand Pharmaceuticals. It is a first generation retinoid. Ligand gained Food and Drug Administration (FDA) approval for alitretinoin in February 1999.
Alternatives to animal testing are the development and implementation of test methods that avoid the use of live animals.
Solar urticaria (SU) is a rare condition in which exposure to ultraviolet or UV radiation, or sometimes even visible light, induces a case of urticaria or hives that can appear in both covered and uncovered areas of the skin. It is classified as a type of physical urticaria. The classification of disease types is somewhat controversial. One classification system distinguished various types of SU based on the wavelength of the radiation that causes the breakout; another classification system is based on the type of allergen that initiates a breakout.
Safety pharmacology is a branch of pharmacology specialising in detecting and investigating potential undesirable pharmacodynamic effects of new chemical entities (NCEs) on physiological functions in relation to exposure in the therapeutic range and above.
Phytophotodermatitis, also known as berloque dermatitis or margarita photodermatitis, is a cutaneous phototoxic inflammatory reaction resulting from contact with a light-sensitizing botanical agent followed by exposure to ultraviolet light. Symptoms include erythema, edema, blisters, and delayed hyperpigmentation. Heat and moisture tend to exacerbate the reaction.
Bergapten (5-methoxypsoralen) is a naturally-occurring organic chemical compound produced by numerous plant species, especially from the carrot family Apiaceae and the citrus family Rutaceae. For example, bergapten has been extracted from 24 species of the genus Heracleum in the family Apiaceae. In the family Rutaceae, various Citrus species contain significant amounts of bergapten, especially the bergamot orange, the micrantha, and certain varieties of lime and bitter orange.
Live-cell imaging is the study of living cells using time-lapse microscopy. It is used by scientists to obtain a better understanding of biological function through the study of cellular dynamics. Live-cell imaging was pioneered in the first decade of the 21st century. One of the first time-lapse microcinematographic films of cells ever made was made by Julius Ries, showing the fertilization and development of the sea urchin egg. Since then, several microscopy methods have been developed to study living cells in greater detail with less effort. A newer type of imaging using quantum dots have been used, as they are shown to be more stable. The development of holotomographic microscopy has disregarded phototoxicity and other staining-derived disadvantages by implementing digital staining based on cells’ refractive index.
Bergamot essential oil is a cold-pressed essential oil produced by cells inside the rind of a bergamot orange fruit. It is a common flavoring and top note in perfumes. The scent of bergamot essential oil is similar to a sweet light orange peel oil with a floral note.