Novel Antioxidant Properties of Doxycycline

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.

In silico Potential of Approved Antimalarial Drugs for Repurposing Against COVID-19

“…6). In addition, downregulation of inflammatory cytokines such as TNF-a, interleukin (IL)-6, and IL-1b also inhibits the cytokine storm (Bahrami et al, 2011;Di Caprio et al, 2015;Dormn et al, 2010) and reduces the cell damage by ROS (Clemens et al, 2018).…”

Protection of the transplant kidney during cold perfusion with doxycycline: proteomic analysis in a rat model

“…Doxy can contribute to protection of mitochondria against ischemic damage in different ways. Except for its potential involvement in energy metabolism, it can inhibit MMP activity (by chelating zinc ion in catalytic site of MMPs [41]), as well as Doxy can directly scavenge ROSsuperoxide [42].…”

Novel Polymeric Nanocarriers Reduced Zinc and Doxycycline Toxicity in the Nematode Caenorhabditis elegans

“…Zinc and doxycycline are antibacterial [9,10] and potent matrix metalloproteinases (MMPs) inhibitors [11], they have also been shown to attenuate the oxidative stress [10,12,13,14]. However, even though zinc is essential for life, zinc may also cause toxicity in cells.…”

“…Hence, exposure to any environmental stress will cause abnormally high ROS, which may lead to the appearancd of oxidative stress and some other various toxic reactions [36]. Oxidative stress happens when ROS level surpasses the endogenous antioxidant defense mechanisms capacity [13]. Even more, ROS may result in pathological periodontal tissue destruction [37], and may also hinder remineralization [38].…”

“…Even more, ROS may result in pathological periodontal tissue destruction [37], and may also hinder remineralization [38]. Zinc and doxycycline has been previously shown to be antioxidants [13,14], but it remains to be ascertained whether they may exert this action after being loaded onto NPs.…”