1. Role of type I & type II reactions in DNA damage and activation of caspase 3 via mitochondrial pathway induced by photosensitized benzophenone.
- Author
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Amar SK, Goyal S, Mujtaba SF, Dwivedi A, Kushwaha HN, Verma A, Chopra D, Chaturvedi RK, and Ray RS
- Subjects
- Apoptosis radiation effects, Benzophenones radiation effects, Cell Line, Cell Survival drug effects, Cytochromes c metabolism, Dose-Response Relationship, Drug, Enzyme Activation, Humans, Hydroxyl Radical metabolism, Keratinocytes enzymology, Keratinocytes pathology, L-Lactate Dehydrogenase metabolism, Lipid Peroxidation drug effects, Membrane Potential, Mitochondrial drug effects, Mitochondria enzymology, Mitochondria pathology, Photolysis, Proto-Oncogene Proteins c-bcl-2 metabolism, Risk Assessment, Signal Transduction, Sunscreening Agents radiation effects, Superoxides metabolism, Ultraviolet Rays, bcl-2-Associated X Protein metabolism, Apoptosis drug effects, Benzophenones toxicity, Caspase 3 metabolism, DNA Breaks, Single-Stranded, Keratinocytes drug effects, Mitochondria drug effects, Oxidative Stress drug effects, Sunscreening Agents toxicity
- Abstract
Sunscreen users have been increased, since excessive sun exposure increased the risk of skin diseases. Benzophenone (BP) and its derivatives are commonly used in sunscreens as UV blocker. Its photosafety is concern for human health. Our study showed the role of type-I and type-II radicals in activation of caspase 3 and phototoxicity of BP under sunlight/UV radiation. BP photodegraded and formed two photoproducts. BP generates reactive oxygen species (ROS) singlet oxygen ((1)O2), superoxide anion (O2˙(-)) and hydroxyl radical (˙OH) through type-I and type-II photodynamic mechanisms. Photocytotoxicity significantly reduced cell viability under sunlight, UVB and UVA. DCF fluorescence confirmed intracellular ROS generation. BP showed single strand DNA breakage, further proved by cyclobutane pyrimidine dimmers (CPDs) formation. Lipid peroxidation and LDH leakage were enhanced by BP. P21 dependent cell cycle study showed sub G1 population which advocates apoptotic cell death, confirmed through AO/EB and annexin V/PI staining. BP decreased mitochondrial membrane potential, death protein released and activated caspase. We proposed cytochrome c regulated caspase 3 dependent apoptosis in HaCaT cell line through down regulation of Bcl2/Bax ratio. Phototoxicity potential of its photoproducts is essential to understand its total environmental fate. Hence, we conclude that BP may replace from cosmetics preparation of topical application., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2015
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