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

Saumya Shukla, Deepti Chopra, Sunil Kumar Patel, Sandeep Negi, Ajeet K Srivastav, Ratnasekhar Ch, Lakshmi Bala, Ashish Dwivedi, Ratan Singh Ray

Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 2022;164():112990

PMID: 35398180

Full Text on Elsevier Science View on PubMed

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 (O) 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.

Address: Photobiology Laboratory, Systems Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India; Department of Biochemistry, College of Dental Sciences, Babu Banarasi Das University, BBD City, Faizabad Road, Lucknow, 226028, Uttar Pradesh, India.; Photobiology Laboratory, Systems Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India.; Photobiology Laboratory, Systems Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India.; CSIR-Central Institute of Medicinal and Aromatic Plants, Kukrail, Picnic Spot Road, Lucknow, 226015, Uttar Pradesh, India.; Department of Biochemistry, College of Dental Sciences, Babu Banarasi Das University, BBD City, Faizabad Road, Lucknow, 226028, Uttar Pradesh, India.; Photobiology Laboratory, Systems Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India. Electronic address: [email protected].; Photobiology Laboratory, Systems Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India; Department of Biochemistry, College of Dental Sciences, Babu Banarasi Das University, BBD City, Faizabad Road, Lucknow, 226028, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India. Electronic address: [email protected].

DOI: 10.1016/j.fct.2022.112990

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MeSH Terms: Apoptosis, Chromatography, Liquid, DNA Damage, Dermatitis, Phototoxic, Hair Dyes, Humans, Keratinocytes, Reactive Oxygen Species, Sulfates, Superoxides, Tandem Mass Spectrometry, Ultraviolet Rays