Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Alexandria University, Elmessalah, 21521, Alexandria, Egypt; Department of Chemistry, University of Alberta, Edmonton, AB, T6G 2G2, Canada.
Pharmaceutical Chemistry Department, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria, Canal El-Mahmoudia Street, Alexandria, Egypt.
J Pharm Biomed Anal. 2020 Aug 5;187:113326. doi: 10.1016/j.jpba.2020.113326. Epub 2020 Apr 27.
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 TbCl. 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. TbCl 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. TbCl 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 TbCl fluorescence with ketoprofen and leflunomide being the most photogenotoxic anti-inflammatory drugs.
据报道，抗炎药物在紫外线照射下会引起核酸的变化。这些变化有可能导致细胞凋亡、癌变和突变。在这项工作中，比较了五种常用的抗炎药物（双氯芬酸、酮洛芬、来氟米特、吡罗昔康和托美汀）在紫外线照射后诱导 DNA 损伤的动力学。研究了包括吸收光谱、MALDI-TOF 质谱和使用 TbCl 的荧光在内的简单、灵敏和环保的 DNA 损伤分析方法。结果表明，所有药物在紫外线照射后都会引起 DNA 损伤。吸收光谱结果表明，DNA 的特征吸收带发生了增色效应，表明双链发生了扭曲。质谱显示，DNA 的分子离子峰显著降低，同时出现较小 m/z 的峰，表明 DNA 链断裂的形成。随着每种药物与 DNA 孵育时间的增加，观察到 TbCl 荧光增加，表明由于损伤，DNA 中出现更多的单链区域。使用 TbCl 荧光获得了诱导损伤的动力学。结果表明，DNA 损伤是通过光诱导的氧化机制发生的。此外，还使用 TbCl 荧光检查了研究药物在小牛胸腺实际 DNA 样品上的效力，结果表明酮洛芬和来氟米特是最具光毒性的抗炎药物。
