Superoxide anion radical induced phototoxicity of 2, 4, 5, 6-Tetraminopyrimidine sulfate via mitochondrial-mediated apoptosis in human skin keratinocytes at ambient UVR exposure. (June 2022)

• Record Type: Journal Article
• Authors: Shukla, Saumya; Chopra, Deepti; Patel, Sunil Kumar; Negi, Sandeep; Srivastav, Ajeet K.; Ch, Ratnasekhar; Bala, Lakshmi; Dwivedi, Ashish; Ray, Ratan Singh
• Is Part Of: Food and chemical toxicology. Volume 164(2022)
• Publication Date: 2022-06
• Subjects: 2, 4, 5, 6-Tetraaminopyrimidine sulfate -- Oxidative stress -- Phototoxicity -- Apoptosis -- DNA damage -- Reactive oxygen species; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2022.112990
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: 2, 4, 5, 6-Tetraaminopyrimidine sulfate (TAPS) is worldwide the most commonly used developer in hair dyes. As skin is the major organ, which is directly exposed to these permanent hair dyes, a comprehensive dermal safety assessment is needed. Hereto, we studied the photosensitization potential and mechanism involved in dermal phototoxicity of TAPS exposed to the dark and UVA/UVB/Sunlight by using different in-chemico and mammalian (HaCaT) cells, as test systems. Our experimental outcomes illustrate that TAPS get photodegraded (LC-MS/MS) and specifically generated superoxide anion radical (O2 − ) under UVA and UVB via type-I photodynamic reaction. The phototoxic potential of TAPS is measured through MTT, NRU, and LDH assays that depicted a significant cell viability reduction at 25 μg/ml concentration and higher. Different cellular stainings (PI uptake, AO/EB, JC-1, NR uptake) suggested the role of mitochondrial-mediated apoptosis. Further, the transcriptomics study revealed upregulation of Apaf-1, Bax, Cytochrome c, Caspase 3, Caspase 9 and downregulation of Catalase and Bcl-2 by TAPS treated cells that strengthen our findings. Thus, the above findings suggest that chronic application of TAPS may be hazardous for human skin and promote various skin diseases. Graphical abstract: The phototoxicity mechanisms showed loss of membrane integrity, reactive oxygen species (ROS)-mediated oxidative stress, photo-induced genotoxicity and mitochondrial-mediated apoptosis, due to photosensitized 2, 4, 5, 6-Tetraaminopyrimidine sulfate (TAPS) treatment under ambient UVR in human skin keratinocytes (HaCaT cell line). Image 1 Highlights: Photodegrdation of TAPS under ambient UVA/UVB and Sunlight. Type –I photodynamic reaction involving superoxide anion radical generation. Cell cycle arrest and cellular organelles (mitochondria, lysosome) membrane damage. Photosensitized TAPS involved in intrinsic mitochondria mediated apoptosis pathway. Apoptosis pathway involved Cytochrome c and caspase cascade pathway.