Accumulation Of Hydroxyl Radicals Research Articles

Ferrocene-Conjugated Paclitaxel Prodrug for Combined Chemo-Ferroptosis Therapy of Cancer.

Herein, we developed a paclitaxel prodrug (PSFc) through the conjugation of paclitaxel (PTX) and ferrocene via a redox-responsive disulfide bond. PSFc displays acid-enhanced catalytic activity of Fenton reaction and is capable of forming stable nanoparticles (PSFc NPs) through the assembly with distearoyl phosphoethanolamine-PEG2000. After being endocytosed, PSFc NPs could release PTX to promote cell apoptosis in response to overexpressed redox-active species of tumor cells. Meanwhile, the ferrocene-mediated Fenton reaction promotes intracellular accumulation of hydroxyl radicals and depletion of glutathione, thus leading to ferroptosis. Compared with the clinically used Taxol, PSFc NPs exhibited more potent in vivo antitumor outcomes through the combined effect of chemotherapy and ferroptosis. This study may offer insight into a facile design of a prodrug integrating different tumor treatment methods for combating malignant tumors.

Prospecting toxicity of the avobenzone sunscreen in plants.

Avobenzone (AVO) is a sunscreen with high global production and is constantly released into the environment. Incorporating sewage biosolids for fertilization purposes, the leaching from cultivated soils, and the use of wastewater for irrigation explain its presence in the soil. There is a lack of information about the impact of this sunscreen on plants. In the present study, the ecotoxicity of AVO was tested at concentrations 1, 10, 100, and 1,000ng/L. All concentrations caused a reduction in root growth of Allium cepa, Cucumis sativus, and Lycopersicum esculentum seeds, as well as a mitodepressive effect, changes in the mitotic spindle and a reduction in root growth of A. cepa bulbs. The cell cycle was disturbed because AVO disarmed the enzymatic defense system of root meristems, leading to an accumulation of hydroxyl radicals and superoxides, besides lipid peroxidation in cells. Therefore, AVO shows a high potential to cause damage to plants and can negatively affect agricultural production and the growth of non-cultivated plants.

Expanding Mn2+ loading capacity of BSA via mild non-thermal denaturing and cross-linking as a tool to maximize the relaxivity of water protons

Development of nanoparticles (NPs) serving as contrast enhancing agents in MRI requires a combination of high contrasting effect with the biosafety and hemocompatibility. This work demonstrates that bovine serum albumin (BSA) molecules bound to paramagnetic Mn2+ ions are promising building blocks of such NPs. The desolvation-induced denaturation of BSA bound with Mn2+ ions followed by the glutaraldehyde-facilitated cross-linking provides the uniform in size 102.0 ± 0.7 nm BSA-based nanoparticles (BSA-NPs) loaded with Mn2+ ions, which are manifested in aqueous solutions as negatively charged spheres with high colloid stability. The optimal loading of Mn2+ ions into BSA-NPs provides maximum values of longitudinal and transverse relaxivity at 98.9 and 133.6 mM−1 s−1, respectively, which are among the best known from the literature. The spin trap EPR method indicates that Mn2+ ions bound to BSA-NPs exhibit poor catalytic activity in the Fenton-like reaction. On the contrary, the presence of BSA-NPs has an antioxidant effect by preventing the accumulation of hydroxyl radicals produced by H2O2. The NPs exhibit remarkably low hemolytic activity and hemagglutination can be avoided at concentrations lower than 110 μM. Thus, BSA-NPs bound with Mn2+ ions are promising candidates for combining high contrast effect with biosafety and hemocompatibility.

Trisulfide Bond-Mediated Molecular Phototheranostic Platform for "Activatable" NIR-II Imaging-Guided Enhanced Gas/Chemo-Hypothermal Photothermal Therapy.

Tumor microenvironment (TME)-triggered phototheranostic platform offers a feasible strategy to improve cancer diagnosis accuracy and minimize treatment side effects. Developing a stable and biocompatible molecular phototheranostic platform for TME-activated second near-infrared (NIR-II) fluorescence imaging-guided multimodal cascade therapy is a promising strategy for creating desirable anticancer agents. Herein, a new NIR-II fluorescence imaging-guided activatable molecular phototheranostic platform (IR-FEP-RGD-S-S-S-Fc) is presented for actively targeted tumor imaging and hydrogen sulfide (H2 S) gas-enhanced chemodynamic-hypothermal photothermal combined therapy (CDT/HPTT). It is revealed for the first time that the coupling distance between IR-FE and ferrocene is proportional to the photoinduced electron transfer (PET), and the aqueous environment is favorable for PET generation. The part of Cyclic-RGDfK (cRGDfk) peptides can target the tumor and benefit the endocytosis of nanoparticles. The high-concentration glutathione (GSH) in the TME will separate the fluorescence molecule and ferrocene by the GSH-sensitive trisulfide bond, realizing light-up NIR-II fluorescence imaging and a cascade of trimodal synergistic CDT/HPTT/gas therapy (GT). In addition, the accumulation of hydroxyl radicals (•OH) and down-regulation of glutathione peroxidase 4 (GPX4) can produce excessive harmful lipid hydroperoxides, ultimately leading to ferroptosis.

Highly dispersed natural Goethite/Fe3O4 heterogeneous Fenton-like catalyst for efficient tetracycline degradation: Rapid accumulation of hydroxyl radicals by Fe–O–Si bonds

A highly dispersed catalyst (Fe3O4/NFe) was prepared with Fe3O4 and natural goethite (NFe) to remove TC in the heterogeneous Fenton-like system. A large amount of ≡Si–O–Si on NFe could be destroyed by the grinding method to produce ≡SiO• on the surface. Fe3O4 nanoparticles were successfully grown on the NFe with the formation of Fe–O–Si bonds, the Fe3O4/NFe retained the magnetic performance and the larger dispersion from predecessors. In the Fe3O4/NFe/H2O2 process, the degradation performance of tetracycline (TC) could reach 90.1% in 30 min. Moreover, the toxicity of TC and its intermediates was estimated in ECOSAR software. The ESR analysis and quenching experiments revealed the contribution of •OH, HO2•, and ≡SiO• in TC removal. A part of •OH, HO2• in solution could decompose TC, and the ≡SiO• on surface also directly remove TC. The strong interactions of Fe–O–Si bonds improved the generation of abundant •OH, and the total concentration of •OH by Fe3O4/NFe in 30 min is 244.7 μmol/L. In DFT analysis, the electrons redistribution between Fe3O4 and NFe could easily provide the electrons to activate H2O2, and improved the adsorption of H2O2 in Fe3O4/NFe/H2O2 system. The removal rate of TC still reached 73.3% by Fe3O4/NFe after five cycles. In the present work, this Fe3O4/NFe has been shown to be a promising alternative to traditional homogeneous Fenton method.

CCCP Facilitates Aminoglycoside to Kill Late Stationary-Phase Escherichia coli by Elevating Hydroxyl Radical.

Improving the efficacy of existing antibiotics is significant for combatting antibiotic resistance that poses a major threat to human health. Carbonyl cyanide m-chlorophenylhydrazine (CCCP), a well-known protonophore for dissipating proton motive force (PMF), has been widely used to block the PMF-dependent uptake of aminoglycoside antibiotics and thus suppress aminoglycoside lethality. Here, we report that CCCP and its functional analog FCCP, but not other types of protonophores, unprecedently potentiate aminoglycosides (e.g., tobramycin and gentamicin) by 3-4 orders of magnitude killing of Escherichia coli, Staphylococcus aureus, Shigella flexneri, and Vibrio alginolyticus cells in stationary phase but not these cells in exponential phase nor other 12 bacterial species we examined. Overall, the effect of CCCP on aminoglycoside lethality undergoes a gradual transition from suppression against E. coli exponential-phase cells to potentiation against late stationary-phase cells, with the cell growth status and culture medium being crucial. Consistently, disturbance of the PMF by changing transmembrane proton gradient (ΔpH) or electric potential (ΔΨ) also potentiates tobramycin. Nevertheless, CCCP neither increases the intracellular concentration of tobramycin nor decreases the MIC of the antibiotic, thus excluding that CCCP acts as an efflux pump inhibitor to potentiate aminoglycosides. Rather, we show that the combined treatment dramatically enhances the cellular level of hydroxyl radical under both aerobic and anaerobic culturing conditions, under which the antioxidant N-acetyl cysteine fully suppresses both hydroxyl radical accumulation and cell death. Together, these findings open a new avenue to develop certain protonophores as aminoglycoside adjuvants against pathogens in stationary phase and also illustrate an essential role of hydroxyl radical in aminoglycoside lethality regardless of aerobic respiration.

A gold nanoparticle engineered metal-organic framework nanoreactor for combined ferroptosis and mild photothermal therapy.

We demonstrate a gold nanoparticle engineered metal-organic framework nanoreactor with photothermal, glucose oxidase-like and GSH-consuming performance to achieve the accumulation of hydroxyl radicals and the enhancement of the thermal sensitivity for combined ferroptosis and mild photothermal therapy.

Nanocatalytic Medicine of Iron-Based Nanocatalysts

Iron can be found in all mammalian cells and is of critical significance to diverse cellular activities within human bodies. Widespread applications and the underlying chemical and biological funda...

LncRNA GABPB1-AS1 and GABPB1 regulate oxidative stress during erastin-induced ferroptosis in HepG2 hepatocellular carcinoma cells

Ferroptosis is a non-apoptotic, iron-dependent oxidative form of cell death that is specifically induced by erastin in RAS mutant cancer cells. Ferroptotic cell death is the result of membrane lipid peroxide damage caused by the accumulation of hydroxyl radicals derived from H2O2 by the Fenton reaction. Peroxidases are key cellular antioxidant enzymes that block such damaging processes. Few studies have examined the roles of long non-coding RNAs (lncRNAs) in the regulation of cellular oxidative stress, especially in ferroptosis. Here, we demonstrated that erastin upregulated the lncRNA GABPB1-AS1, which downregulated GABPB1 protein levels by blocking GABPB1 translation, leading to the downregulation of the gene encoding Peroxiredoxin-5 (PRDX5) peroxidase and the eventual suppression of the cellular antioxidant capacity. Such effects critically inhibited the cellular antioxidant capacity and cell viability. Additionally, high expression levels of GABPB1 were correlated with poor prognosis of hepatocellular carcinoma (HCC) Patients, while high GABPB1-AS1 levels in HCC patients correlated with improved overall survival. Collectively, these data demonstrate a mechanistic link between GABPB1 and its antisense lncRNA GABPB1-AS1 in erastin-induced ferroptosis and establish GABPB1 and GABPB1-AS1 as attractive therapeutic targets for HCC.

Improvement of the Electrochemical Behavior of (Sb, Sn, Cu)O Ceramic Electrodes as Electrochemical Advanced Oxidation Anodes

AbstractThis work explores the possibility of increasing the active surface of a Sb‐doped SnO2 ceramic electrode using CuO as sintering aid, by incorporating petroleum coke as a pore generator. In order to fulfil this goal, three series of (Sb, Sn, Cu)O electrodes with different coke contents were synthetized. The properties of the electrodes, and their microstructure, change significantly as a function of the coke content before sintering. The electrochemical characterization of the synthesized electrodes showed that the coke addition before sintering causes two antagonist effects on the performance of the (Sn, Sb, Cu)O as anodes in electrochemical advanced oxidation processes (EAOP). On one hand, it significantly improves the electrochemical roughness factor of the electrode, solving the densification problem in this way. On the other hand, it worsens the electrochemical behavior of the electrode: narrowing its electrochemical window; and “activating” it slightly. The addition of coke before sintering changes the kinetic parameters, leading to a kinetic situation in which the accumulation of hydroxyl radicals is slightly lower. A balance must be sought: an intermediate coke content will improve significantly the electrochemical roughness factor of the electrode, but will only worsen slightly its electrochemical behavior, leading to an optimum (Sn, Sb, Cu)O EAOP anode.

CuO improved (Sn,Sb)O2 ceramic anodes for electrochemical advanced oxidation processes

AbstractAntimony‐doped tin oxide electrodes with CuO as sintering aid are presented as an economical alternative to metal‐based electrodes, intended for the electrooxidation process of emerging and recalcitrant organic contaminants in wastewaters. The CuO proportion has been optimized to obtain densified electrodes with a mild thermal cycle (Tmax = 1200°C). One of the manufactured electrodes (97.8 mol.% of SnO2, 1.0 mol.% of Sb2O3, and 1.2 mol.% of CuO) was selected for electrochemical characterization from a physical and morphological analysis. The electrochemical behavior of the selected electrode showed that the addition of CuO as sintering aid widens the electrochemical window and increases the electrode “inactivity”, with respect to an (Sn, Sb)O2 electrode synthesized in the same conditions. In return, the (Sn,Sb,Cu)O2 electrode presents a significantly lower electrochemical rugosity factor. Moreover, the addition of CuO does not change the oxygen evolution reaction mechanism, but it modifies the kinetic parameters, leading to a larger accumulation of hydroxyl radicals. Consequently, the addition of CuO as sintering aid significantly improves the electrochemical properties of the electrode as an electrochemical advanced oxidation process anode with respect to the (Sn,Sb)O2 electrode, at the expense of worsening its electrochemical roughness factor. The results of the electrochemical characterization were confirmed by Norfloxacin degradation tests.

Hydrogen-rich pure water prevents cigarette smoke-induced pulmonary emphysema in SMP30 knockout mice

Chronic obstructive pulmonary disease (COPD) is predominantly a cigarette smoke (CS)-triggered disease with features of chronic systemic inflammation. Oxidants derived from CS can induce DNA damage and stress-induced premature cellular senescence in the respiratory system, which play significant roles in COPD. Therefore, antioxidants should provide benefits for the treatment of COPD; however, their therapeutic potential remains limited owing to the complexity of this disease. Recently, molecular hydrogen (H2) has been reported as a preventive and therapeutic antioxidant. Molecular H2 can selectively reduce hydroxyl radical accumulation with no known side effects, showing potential applications in managing oxidative stress, inflammation, apoptosis, and lipid metabolism. However, there have been no reports on the efficacy of molecular H2 in COPD patients. In the present study, we used a mouse model of COPD to investigate whether CS-induced histological damage in the lungs could be attenuated by administration of molecular H2. We administered H2-rich pure water to senescence marker protein 30 knockout (SMP30-KO) mice exposed to CS for 8 weeks. Administration of H2-rich water attenuated the CS-induced lung damage in the SMP30-KO mice and reduced the mean linear intercept and destructive index of the lungs. Moreover, H2-rich water significantly restored the static lung compliance in the CS-exposed mice compared with that in the CS-exposed H2-untreated mice. Moreover, treatment with H2-rich water decreased the levels of oxidative DNA damage markers such as phosphorylated histone H2AX and 8-hydroxy-2′-deoxyguanosine, and senescence markers such as cyclin-dependent kinase inhibitor 2A, cyclin-dependent kinase inhibitor 1, and β-galactosidase in the CS-exposed mice. These results demonstrated that H2-rich pure water attenuated CS-induced emphysema in SMP30-KO mice by reducing CS-induced oxidative DNA damage and premature cell senescence in the lungs. Our study suggests that administration of molecular H2 may be a novel preventive and therapeutic strategy for COPD.

ZntR positively regulates T6SS4 expression in Yersinia pseudotuberculosis.

The type VI secretion system (T6SS) is a widespread and versatile protein secretion system found in most Gram-negative bacteria. Studies of T6SS have mainly focused on its role in virulence toward host cells and inter-bacterial interactions, but studies have also shown that T6SS4 in Yersinia pseudotuberculosis participates in the acquisition of zinc ions to alleviate the accumulation of hydroxyl radicals induced by multiple stressors. Here, by comparing the gene expression patterns of wild-type and zntR mutant Y. pseudotuberculosis cells using RNA-seq analysis, T6SS4 and 17 other biological processes were found to be regulated by ZntR. T6SS4 was positively regulated by ZntR in Y. pseudotuberculosis, and further investigation demonstrated that ZntR regulates T6SS4 by directly binding to its promoter region. T6SS4 expression is regulated by zinc via ZntR, which maintains intracellular zinc homeostasis and controls the concentration of reactive oxygen species to prevent bacterial death under oxidative stress. This study provides new insights into the regulation of T6SS4 by a zinc-dependent transcriptional regulator, and it provides a foundation for further investigation of the mechanism of zinc transport by T6SS.

Potentiostatic activation of as-made graphene electrodes for high-rate performance in supercapacitors

Abstract A thermally expanded graphene oxide (EGO) electrode is electrochemically activated to simultaneously introduce electrolyte-accessible mesopores and oxygen functional groups. The former is produced via O 2 evolution and the latter is incorporated by the intermediate hydroxyl radicals generated during the potentiostatic oxidation of H 2 O in 1 M H 2 SO 4 at 1.2 V (vs. Ag/AgCl). When applied as a supercapacitor, the potentiostatically treated EGO (EGO-PS) shows significant enhancement in an electric-double layer (EDL) process with a noticeable Faradaic reaction and delivers high capacitance at fast charge/discharge (C/D) rates (334 F g −1 at 0.1 A g −1 and 230 F g −1 at 50 A g −1 ). In contrast to EGO-PS, EGO that is oxidized potentiodynamically (EGO-PD) shows negligible enhancement in EDL currents. EGO that is subjected to successive potential pulses also shows behaviors similar to EGO-PD, which indicates the importance of hydroxyl radical accumulation via a potentiostatic method for simultaneous functionalization and microstructural control of graphenes. The potentiostatic post-treatment presented here is a convenient post-treatment strategy that could be used to readily increase capacitance and simultaneously improve the high-rate performance of carbon-based electrodes.

Haptoglobin: an emerging candidate for phenotypic modulation of sickle cell anemia?

Sickle cell anemia (SCA) is characterized by a single homozygous mutation (A→T) in the sixth codon of the -globin gene that results in hemoglobin S (Hb S), in which a glutamic acid residue is substituted by valine in the sixth position of the -globin chain (HBB; glu(E)6val(A); GAG-GTG; rs334).1 This change leads to a wide variety of symptoms, including chronic intravascular hemolysis, increased cell-free plasma hemoglobin (Hb) and heme levels and vascular alterations.2 SCA has been characterized as a chronic inflammatory state with abnormal endothelial activation as a result of various associated factors. The mechanisms that induce the production of inflammatory mediators and the effects of these molecules on the inflammatory response are little understood in this disease.3 Sickled red blood cells are stiff and therefore have a predisposition to hemolysis; one third of the cells are destroyed in the intravascular space leading to increased cell-free plasma Hb and heme levels.4 The pathophysiological effects associated with free Hb/heme are acute hemodynamic instability and acute or chronic vascular injury.5 The toxicity and inflammatory nature of free Hb are a result of the greater nitric oxide consumption it promotes and the consequent accumulation of hydroxyl radicals and reactive oxygen species in the blood vessels. The organism’s first defense mechanism against the harmful effects of free Hb involves haptoglobin (Hp), whose primary function is to bind to free Hb in the plasma, thereby preventing the excretion of iron by the kidneys and protecting blood vessels from its oxidative effects.6,7 In addition to being an antioxidant, Hp is a positive acute-phase glycoprotein present in plasma with immunomodulatory properties.6,7

Delayed hyperoxic ventilation attenuates oxygen-induced free radical accumulation during early reperfusion after global brain ischemia.

To compare the effect of immediate and delayed administration of oxygen on the accumulation of free radicals in ischemia-reperfusion animal models. Thirty-two adult male Mongolian gerbils with microdialysis probes implanted in the right hippocampal CA1 were divided randomly into four groups (eight each). One group was sham-operated (Sham group) whereas the other three groups were subjected to 10 min bilateral carotid artery occlusion (BCAO). BCAO-treated animals were then subjected to the following: (a) immediate 30% O2 (near normoxia, NO group), (b) immediate 100% O2 (hyperoxia, HO group), and (c) 30% O2 for 60 min, followed by 100% O2 for 60 min (delayed hyperoxia, DHO group). Hippocampal accumulation of hydroxyl radicals (•OH) during reperfusion was estimated by measuring 2,3-dihydroxybenzoic acid (DHBA) and 2,5-DHBA in microdialysis perfusate. Hippocampi were removed 2 h after perfusion to measure malondialdehyde, pyruvate dehydrogenase activity, indices of lipid peroxidation, and cellular respiration. At 24 h after BCAO, the histology of hippocampi was analyzed to rate the injury. Immediately after the onset of reperfusion, all groups showed markedly elevated DHBA, which returned to baseline over 1-2 h. Compared with the NO group, the HO group showed significantly higher peak DHBA and slower recovery. In contrast, the DHO group was not significantly different from the NO group in terms of the DHBA level. DHO animals also showed significantly lower hippocampal malondialdehyde accumulation and higher pyruvate dehydrogenase activity at 2 h after reperfusion versus the HO group. Histology analysis also showed animals in the DHO group with ameliorated injury compared with the HO group. Hydroxyl radical accumulation was more sensitive to O2 during early reperfusion. Delayed hyperoxia may re-establish oxidative metabolism while minimizing oxidative stress after CA.

Ribosomal elongation factor 4 promotes cell death associated with lethal stress.

ABSTRACTRibosomal elongation factor 4 (EF4) is highly conserved among bacteria, mitochondria, and chloroplasts. However, the EF4-encoding gene, lepA, is nonessential and its deficiency shows no growth or fitness defect. In purified systems, EF4 back-translocates stalled, posttranslational ribosomes for efficient protein synthesis; consequently, EF4 has a protective role during moderate stress. We were surprised to find that EF4 also has a detrimental role during severe stress: deletion of lepA increased Escherichia coli survival following treatment with several antimicrobials. EF4 contributed to stress-mediated lethality through reactive oxygen species (ROS) because (i) the protective effect of a ΔlepA mutation against lethal antimicrobials was eliminated by anaerobic growth or by agents that block hydroxyl radical accumulation and (ii) the ΔlepA mutation decreased ROS levels stimulated by antimicrobial stress. Epistasis experiments showed that EF4 functions in the same genetic pathway as the MazF toxin, a stress response factor implicated in ROS-mediated cell death. The detrimental action of EF4 required transfer-messenger RNA (tmRNA, which tags truncated proteins for degradation and is known to be inhibited by EF4) and the ClpP protease. Inhibition of a protective, tmRNA/ClpP-mediated degradative activity would allow truncated proteins to indirectly perturb the respiratory chain and thereby provide a potential link between EF4 and ROS. The connection among EF4, MazF, tmRNA, and ROS expands a pathway leading from harsh stress to bacterial self-destruction. The destructive aspect of EF4 plus the protective properties described previously make EF4 a bifunctional factor in a stress response that promotes survival or death, depending on the severity of stress.

Moving forward with reactive oxygen species involvement in antimicrobial lethality.

Support for the contribution of reactive oxygen species (ROS) to antimicrobial lethality has been refined and strengthened. Killing by diverse antimicrobials is enhanced by defects in genes that protect against ROS, inhibited by compounds that block hydroxyl radical accumulation, and is associated with surges in intracellular ROS. Moreover, support has emerged for a genetic pathway that controls the level of ROS. Since some antimicrobials kill in the absence of ROS, ROS must add to, rather than replace, known killing mechanisms. New work has addressed many of the questions concerning the specificity of dyes used to detect intracellular ROS and the specificity of perturbations that influence ROS surges. However, complexities associated with killing under anaerobic conditions remain to be resolved. Distinctions among primary lesion formation, resistance, direct lesion-mediated killing and a self-destructive stress response are discussed to facilitate efforts to potentiate ROS-mediated bacterial killing and improve antimicrobial efficacy.

Lethal Hydroxyl Radical Accumulation by a Lactococcal Bacteriocin, Lacticin Q

The antimicrobial mechanism of a lactococcal bacteriocin, lacticin Q, can be described by the toroidal pore model without any receptor. However, lacticin Q showed different degrees of activity (selective antimicrobial activity) against Gram-positive bacteria even among related species. The ability of lacticin Q to induce pore formation in liposomes composed of lipids from different indicator strains indicated that its selective antimicrobial activity could not be attributed only to membrane lipid composition. We investigated the accumulation of deleterious hydroxyl radicals after exposure to lacticin Q as a contributing factor to cell death in the indicator strains. When lacticin Q of the same concentration as the MIC or minimum bactericidal concentration was added to the indicator cultures, high levels of hydroxyl radical accumulation were detected. Treatment with hydroxyl radical scavengers, thiourea and 2,2'-bipyridyl, decreased the levels of hydroxyl radical accumulation and recovered cell viability. These results suggest that, with or without pore formation, the final antimicrobial mechanism of lacticin Q is the accumulation of hydroxyl radicals, which varies by strain, resulting in the selective antimicrobial activity of lacticin Q.

Inhibitors of Reactive Oxygen Species Accumulation Delay and/or Reduce the Lethality of Several Antistaphylococcal Agents

Perturbation of hydroxyl radical accumulation by subinhibitory concentrations of 2,2'-bipyridyl plus thiourea protects Escherichia coli from being killed by 3 lethal antimicrobial classes. Here, we show that 2,2'-bipyridyl plus thiourea delays and/or reduces antimicrobial killing of Staphylococcus aureus by daptomycin, moxifloxacin, and oxacillin. While the protective effect of 2,2'-bipyridyl plus thiourea varied among strains and compounds, the data support the hypothesis that hydroxyl radical enhances antimicrobial lethality.