Novel Antioxidant Properties of Doxycycline

Authors

Dahn L. Clemens, University of Nebraska Medical CenterFollow
Michael J. Duryee, University of Nebraska Medical CenterFollow
Cleofes Sarmiento, University of Nebraska Medical CenterFollow
Andrew Chiou, University of Nebraska Medical CenterFollow
Jacob D. McGowan, University of Nebraska Medical CenterFollow
Carlos D. Hunter, University of Nebraska Medical CenterFollow
Sarah L. Schlichte, University of Nebraska Medical CenterFollow
Jun Tian, University of Nebraska Medical CenterFollow
Lynell W. Klassen, University of Nebraska Medical CenterFollow
James R. O'Dell, University of Nebraska Medical CenterFollow
Geoffrey M. Thiele, University of Nebraska Medical CenterFollow
Ted R. Mikuls, University of Nebraska Medical CenterFollow
Matthew C. Zimmerman, University of Nebraska Medical CenterFollow
Daniel R. Anderson, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

International Journal of Molecular Sciences

Publication Date

2018

Volume

19

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.

DOI Link

10.3390/ijms19124078

ISSN

1422-0067

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Clemens, Dahn L.; Duryee, Michael J.; Sarmiento, Cleofes; Chiou, Andrew; McGowan, Jacob D.; Hunter, Carlos D.; Schlichte, Sarah L.; Tian, Jun; Klassen, Lynell W.; O'Dell, James R.; Thiele, Geoffrey M.; Mikuls, Ted R.; Zimmerman, Matthew C.; and Anderson, Daniel R., "Novel Antioxidant Properties of Doxycycline" (2018). Journal Articles: Cellular & Integrative Physiology. 33.
https://digitalcommons.unmc.edu/com_cell_articles/33