Abstract

Doxycycline (DOX), a derivative of tetracycline, is a broad-spectrum antibiotic that exhibits a number of therapeutic activities in addition to its antibacterial properties. For example, DOX has been used in the management of a number of diseases characterized by chronic inflammation. One potential mechanism by which DOX inhibits the progression of these diseases is by reducing oxidative stress, thereby inhibiting subsequent lipid peroxidation and inflammatory responses. Herein, we tested the hypothesis that DOX directly scavenges reactive oxygen species (ROS) and inhibits the formation of redox-mediated malondialdehyde-acetaldehyde (MAA) protein adducts. Using a cell-free system, we demonstrated that DOX scavenged reactive oxygen species (ROS) produced during the formation of MAA-adducts and inhibits the formation of MAA-protein adducts. To determine whether DOX scavenges specific ROS, we examined the ability of DOX to directly scavenge superoxide and hydrogen peroxide. Using electron paramagnetic resonance (EPR) spectroscopy, we found that DOX directly scavenged superoxide, but not hydrogen peroxide. Additionally, we found that DOX inhibits MAA-induced activation of Nrf2, a redox-sensitive transcription factor. Together, these findings demonstrate the under-recognized direct antioxidant property of DOX that may help to explain its therapeutic potential in the treatment of conditions characterized by chronic inflammation and increased oxidative stress.

Original languageEnglish (US)
Article number4078
JournalInternational journal of molecular sciences
Volume19
Issue number12
DOIs
StatePublished - Jan 1 2018

Fingerprint

Acetaldehyde
Doxycycline
acetaldehyde
antioxidants
Antioxidants
adducts
Oxidative stress
inorganic peroxides
hydrogen peroxide
Hydrogen peroxide
Oxygen
Malondialdehyde
oxygen
tetracyclines
proteins
Proteins
Transcription factors
antibiotics
peroxides
Antibiotics

Keywords

  • Anti-oxidant
  • Doxycycline
  • Electron paramagnetic resonance
  • Oxidative stress
  • Post transnational modification

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Novel antioxidant properties of doxycycline. / Clemens, Dahn L; Duryee, Michael J.; Sarmiento, Cleofes; Chiou, Andrew; McGowan, Jacob D.; Hunter, Carlos D.; Schlichte, Sarah L.; Tian, Jun; Klassen, Lynell Warren; O'Dell, James Robert; Thiele, Geoffrey Milton; Mikuls, Ted R; Zimmerman, Matthew C; Anderson, Daniel R.

In: International journal of molecular sciences, Vol. 19, No. 12, 4078, 01.01.2018.

Research output: Contribution to journalArticle

Clemens DL, Duryee MJ, Sarmiento C, Chiou A, McGowan JD, Hunter CD et al. Novel antioxidant properties of doxycycline. International journal of molecular sciences. 2018 Jan 1;19(12). 4078. https://doi.org/10.3390/ijms19124078
Clemens, Dahn L ; Duryee, Michael J. ; Sarmiento, Cleofes ; Chiou, Andrew ; McGowan, Jacob D. ; Hunter, Carlos D. ; Schlichte, Sarah L. ; Tian, Jun ; Klassen, Lynell Warren ; O'Dell, James Robert ; Thiele, Geoffrey Milton ; Mikuls, Ted R ; Zimmerman, Matthew C ; Anderson, Daniel R. / Novel antioxidant properties of doxycycline. In: International journal of molecular sciences. 2018 ; Vol. 19, No. 12.
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