Acetaminophen, the Active Ingredient of Tylenol, Protects against Peroxynitrite-Induced DNA Damage: A Chemiluminometric and Electron Paramagnetic Resonance Spectrometric Study

Authors

  • Xueqing Dou Presently at Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China
  • Jason Z. Li Presently at University of Virginia, Charlottesville, VA 22903, USA
  • Igor Danelisen Campbell University School of Osteopathic Medicine, Buies Creek, NC 27506, USA
  • Michael A. Trush Department of Environmental Health Sciences, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA
  • Hara P. Misra Virginia Tech CRC Research Building II, Blacksburg, VA 24060, USA
  • Hong Zhu Campbell University School of Osteopathic Medicine, Buies Creek, NC 27506, USA
  • Zhenquan Jia Campbell University School of Osteopathic Medicine, Buies Creek, NC 27506, USA; Department of Biology, University of North Carolina, Greensboro, NC 27412, USA
  • Y. Robert Li Campbell University School of Osteopathic Medicine, Buies Creek, NC 27506, USA; Department of Biology, University of North Carolina, Greensboro, NC 27412, USA; Virginia Tech‒Wake Forest University School of Biomedical Engineering and Sciences, Blacksburg, VA 24061, USA; Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA

Keywords:

Acetaminophen, Chemiluminometry, DNA damage, Electron paramagnetic resonance, Peroxynitrite, SIN-1, Spin-trapping

Abstract

This study investigated the hypothesis that acetaminophen at pharmacologically relevant concentrations may act as a protector against peroxynitrite toxicity.  Our results showed that acetaminophen inhibited SIN-1 (a peroxynitrite generator)-induced DNA cleavage in a concentration-dependent manner in an in vitro model. With bicarbonate-enhanced luminol-dependent chemiluminometry, we further showed a nearly complete blockage of peroxynitrite-derived chemiluminescence by acetaminophen at 25‒100 µM with minimal effects on SIN-1-mediated oxygen consumption, suggesting acetaminophen as a potent scavenger of peroxynitrite. Electron spin resonance spectrometry in combination with 5,5-dimethyl-1-pyrroline N-oxide (DMPO)-spin-trapping supported the ability of acetaminophen at high concentrations to diminish the production of a free radical species (likely hydroxyl radical) from SIN-1. Fenton chemistry-based DMPO-spin trapping further demonstrated the hydroxyl radical-scavenging capacity of acetaminophen. Collectively, the results of this study for the first time revealed the potential of acetaminophen to protect against peroxyitrite toxicity, which may have important implications in neuroprotection associated with the use of this popular analgesic and antipyretic drug.

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Published

2017-03-01

How to Cite

Dou, X., Li, J. Z., Danelisen, I., Trush, M. A., Misra, H. P., Zhu, H., Jia, Z., & Li, Y. R. (2017). Acetaminophen, the Active Ingredient of Tylenol, Protects against Peroxynitrite-Induced DNA Damage: A Chemiluminometric and Electron Paramagnetic Resonance Spectrometric Study. Reactive Oxygen Species, 3(8), 127–134. Retrieved from https://rosj.org/index.php/ros/article/view/83

Issue

Vol. 3 No. 8 (2017)

Section

ORIGINAL RESEARCH

License

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