Abstract
Doxycycline (DOXY) is an antibiotic routinely prescribed in human and veterinary medicine for antibacterial treatment, but it has also numerous side effects that include oxidative stress, inflammation, cancer or hypoxia-induced injury. Endogenously produced hydrogen sulfide (H2S) and polysulfides affect similar biological processes, in which reactive oxygen species (ROS) play a role. Herein, we have studied the interaction of DOXY with H2S (Na2S) or polysulfides (Na2S2, Na2S3 and Na2S4) to gain insights into the biological effects of intermediates/products that they generate. To achieve this, UV-VIS, EPR spectroscopy and plasmid DNA (pDNA) cleavage assay were employed. Na2S or Na2S2 in a mixture with DOXY, depending on ratio, concentration and time, displayed bell-shape kinetics in terms of producing/scavenging superoxide and hydroxyl radicals and decomposing hydrogen peroxide. In contrast, the effects of individual compounds (except for Na2S2) were hardly observable. In addition, DOXY, as well as oxytetracycline and tetracycline, interacting with Na2S or other studied polysulfides reduced the •cPTIO radical. Tetracyclines induced pDNA cleavage in the presence of Na2S. Interestingly, they inhibited pDNA cleavage induced by other polysulfides. In conclusion, sulfide and polysulfides interacting with tetracyclines produce/scavenge free radicals, indicating a consequence for free radical biology under conditions of ROS production and tetracyclines administration.
Highlights
IntroductionProduced hydrogen sulfide (H2 S) and polysulfides (H2 Sn ) affect many physiological and pathological processes, such as hypertension, atherosclerosis, heart failure, diabetes, inflammation, asthma, burn injuries, sepsis, angiogenesis, cancer, and neurodegenerative diseases.H2 S and H2 Sn have the beneficial effects under conditions of oxidative stress by reacting with reactiveMolecules 2019, 24, 1148; doi:10.3390/molecules24061148 www.mdpi.com/journal/moleculesMolecules 2019, 24, 1148 oxygen (ROS) and nitrogen (RNS) species, causing radical-induced DNA damage or possessing anti-cancer and, in some cases, pro-cancer activities [1,2,3,4,5,6,7,8,9,10,11,12,13]
Do hydrogen sulfide (H2 S) and/or polysulfides interact with tetracyclines (DOXY, OXYT or TETR)? Since both tetracyclines and H2 S/polysulfides were reported to induce reactive oxygen species (ROS) or, in contrary, have the beneficial effects against ROS-caused damage [8,29,30,31,32,33], we wondered whether interaction of
If H2 S/polysulfides interact with tetracyclines, do intermediates/products of the interaction have the biological effects in vitro and in vivo? We found that H2 S/polysulfides interact with tetracyclines leading to free radical producing/scavenging processes
Summary
Produced hydrogen sulfide (H2 S) and polysulfides (H2 Sn ) affect many physiological and pathological processes, such as hypertension, atherosclerosis, heart failure, diabetes, inflammation, asthma, burn injuries, sepsis, angiogenesis, cancer, and neurodegenerative diseases.H2 S and H2 Sn have the beneficial effects under conditions of oxidative stress by reacting with reactiveMolecules 2019, 24, 1148; doi:10.3390/molecules24061148 www.mdpi.com/journal/moleculesMolecules 2019, 24, 1148 oxygen (ROS) and nitrogen (RNS) species, causing radical-induced DNA damage or possessing anti-cancer and, in some cases, pro-cancer activities [1,2,3,4,5,6,7,8,9,10,11,12,13]. DOXY induces cell death, has an anti-apoptotic function or induces apoptosis, reduces or induces ROS, triggers inflammation, reduces cardiac attack, protects cells or renal function from hypoxia-induced injury, prevents proliferation, reduces tumor growth, and suppresses a process of metastasis in human breast or prostate cancer models (for a review see [22,23,24,25,26,27]). Molecular mechanisms of these tetracyclines’ side effects are not fully understood yet and remain to be examined thoroughly
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