Sensitive spectrofluorimetric and mass spectroscopic methods for the determination of nucleic acid damage induced by photosensitized anti-inflammatory drugs: Comparative study

[Display omitted] •Analysis of the DNA damage induced due to interaction of DNA with different NSAIDs.•The studied drugs are diclofenac, ketoprofen, leflunomide, piroxicam and tolmetin.•Using Absorbance, mass spectrometry and fluorimetric probes for DNA damage analysis.•The kinetics of DNA damage in...

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Veröffentlicht in:Journal of pharmaceutical and biomedical analysis 2020-08, Vol.187, p.113326, Article 113326
Hauptverfasser: El-Yazbi, Amira F., Guirguis, Karin M., Belal, Tarek S., Bedair, Mona M.
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Sprache:eng
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Zusammenfassung:[Display omitted] •Analysis of the DNA damage induced due to interaction of DNA with different NSAIDs.•The studied drugs are diclofenac, ketoprofen, leflunomide, piroxicam and tolmetin.•Using Absorbance, mass spectrometry and fluorimetric probes for DNA damage analysis.•The kinetics of DNA damage induced by the drugs after UVA irradiation were studied.•Determination of the minimum amount of the drug that induce DNA damage. Anti-inflammatory drugs are reported to induce changes in nucleic-acids upon UV-irradiation. Such changes have the potential to cause apoptosis, carcinogenesis, and mutagenesis. In this work, the kinetics of the damage induced in DNA by some anti-inflammatory drugs were compared after UV-irradiation. Five commonly used anti-inflammatory drugs; diclofenac, ketoprofen, leflunomide, piroxicam and tolmetin, were studied. Simple, sensitive and eco-friendly methods for the analysis of DNA-damage were proposed including absorption spectroscopy, MALDI-TOF mass spectrometry and fluorescence using TbCl3. Results show that all drugs induced DNA-damage after UV-irradiation. Absorption spectroscopy results demonstrated hyperchromic shift in the absorption band characteristic to DNA, indicating distortion of the double-strand. Mass spectra showed a significant decrease of the molecular-ion-peak of DNA, together with peaks of smaller m/z that indicated the formation of DNA strand-breaks. TbCl3 fluorescence was observed to increase with incubation time of each drug with DNA, indicating the presence of more single-stranded regions in DNA due to damage. TbCl3 fluorescence was used to obtain the kinetics of the induced damage. Results show that DNA-damage occurred via photoinduced oxidative mechanism. Also, the potency of the studied drugs was examined on calf-thymus real DNA samples using TbCl3 fluorescence with ketoprofen and leflunomide being the most photogenotoxic anti-inflammatory drugs.
ISSN:0731-7085
1873-264X
DOI:10.1016/j.jpba.2020.113326