Novel Antioxidant Properties of Doxycycline

• Published in: International journal of molecular sciences Vol. 19; no. 12; p. 4078
• Main Authors: 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, Anderson, Daniel R
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.12.2018; MDPI
• Subjects: Acetaldehyde; Adducts; anti-oxidant; Antibiotics; Antioxidants; Cell-Free System; Doxycycline; Doxycycline - chemistry; Doxycycline - pharmacology; Electron paramagnetic resonance; Electron spin resonance; Free Radical Scavengers - chemistry; Free Radical Scavengers - pharmacology; HEK293 Cells; Humans; Hydrogen peroxide; Hydrogen Peroxide - chemistry; Hydrogen Peroxide - metabolism; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Inflammatory diseases; Lipid peroxidation; Lipids; Malondialdehyde; Malondialdehyde - chemistry; Malondialdehyde - metabolism; NF-E2-Related Factor 2 - metabolism; Oxidative stress; Oxidative Stress - drug effects; Pharmaceuticals; post transnational modification; Protein adducts; Proteins; Spectroscopy; Spectrum analysis; Superoxide; Superoxides - chemistry; Superoxides - metabolism; Transcription factors; post transnational modification; anti-oxidant; electron paramagnetic resonance; doxycycline; oxidative stress
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19124078

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.