Free Radical Species Research Articles

Current State of the Art on the Antioxidant Activity of Sage (Salvia spp.) and Its Bioactive Components.

Common sage (Salvia spp., with the most common species Salvia officinalis) is an important medicinal and aromatic plant due to its bioactive components, secondary products of its metabolism. These components are mainly phenolics, terpenoids, polyphenols, and flavonoids. Many studies have identified their important role in fighting oxidative stress in cells and organisms, together with their anticancer, antimicrobial, and anti-inflammatory role. There are many methods measuring the antioxidant activity of sage phenolic components, usually based on radical scavenging of free radical species, such as 2,2-diphenyl-1-picrylydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and determining the absorbance of the reduced product by a photometric assay. In addition, there are several in vitro and in vivo studies determining the protection of sage extracts in cells in culture or animals, respectively, after induction of oxidative stress. In this review, results from the currently available studies that unravel the significant role of sage bioactive compounds, as antioxidant compounds, and the variety of methods used have been critically analyzed and discussed.

Synthesis, DFT, computational exploration of chemical reactivity, molecular docking studies of novel formazan metal complexes and their biological applications

The computational exploration of chemical reactivity and molecular docking of the synthesized formazan compounds (S1‐S6) were studied. Further, their antimicrobial activity against bacterial strains (S. epidermidis, B. cereus, K. pneumoniae and P. aeruginosa) and against fungal strains (T. mentagrophytes, C. albicans, A. niger, S. cerevisiae and C. glabrata) using agar diffusion method and antioxidant activity following DPPH inhibition assays were evaluated. Anticancer activity was executed in vitro model of human breast carcinoma (MCF‐7) cell line. The superior and enhanced antibacterial and antimycotic activities were exhibited by formazan compound (S4) by presenting maximum ZOIs and MICs values. While enhanced antioxidant in terms of percentage inhibition of DPPH and cytotoxic effect on human breast carcinoma‐cells demonstrated by formazan compound (S1) which was further validated by the results of molecular docking studies of (S1) with the human estrogen receptor protein. In order to compute quantum chemical reactivity descriptors from conceptual density functional theory (CDFT) point of view of this system, including chemical potential (μ), chemical hardness (η), electrophilicity (ω), condensed Fukui function and dual descriptors are calculated at the same level of calculation. The most active sites of these molecules are determined and correlated with experimental data. The present investigation displays that formazans compounds could be potential drug candidate that constrains the growth of microbial strains, possess ability to cause cytotoxic effect on carcinoma cells and act as effective scavenger for free radical species.

Highly Efficient Aerobic Oxidation of Cyclohexene Catalyzed by Iron(III) Porphyrins in Supercritical Carbon Dioxide

Efficient aerobic oxidation of cyclohexene to the corresponding products catalyzed by iron (III) porphyrins in supercritical carbon dioxide (scCO2) has been developed. Compared with the oxidation occurred in dichloroethane, the efficiency was improved significantly in scCO2, in which the cyclohexene conversion increased from 10.5% to 22.4%. Influence of various reaction parameters including catalyst, catalyst dosage, reaction temperature and pressure on the activity and selectivity were investigated in detail. Moreover, a plausible mechanism involving free radical and high-valence iron species was proposed.

An Update on the Role of Nrf2 and its Activators in Diseases Associated with Oxidative Stress

A wide range of experimental and observational studies have established the irrefutable role of oxidative stress in the pathogenesis of a plethora of diseases either directly or indirectly. Several factors ranging from radiation, pollution, high fat and sugar diet, alcohol consumption, smoking, tobacco consumption and even certain drugs contribute to oxidative stress. The imbalance between oxidant and antioxidant levels remain the underlying cause of oxidative stress. When the levels of oxidants outweigh the levels of antioxidants it leads to formation of free radicals like hydroxyl, superoxide, alkoxyl, peroxyl, glutathiyl, tocopheroxyl, hydroperoxyl and ascorbate. These free radical species play a definitive role in the pathogenesis of neurological diseases, malignancies, cardiovascular, respiratory and liver diseases. Nuclear factor erythroid-2-related factor 2 is a master transcription factor belonging to the leucine zipper family. Kelch-like ECH-associated protein 1 is a repressor of nuclear factor erythroid-2-related factor 2 under basal or normal conditions, which is responsible for cytoplasmic sequestration and proteosomal degradation of nuclear factor erythroid-2-related factor 2 via ubiquitination. The activation of nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1/antioxidant response element signalling pathway regulates the expression of numbers of genes that are cytoprotective, antioxidative and detoxificative in action. This article reviews the potential therapeutic role of nuclear factor erythroid-2-related factor 2 activators in prevention and treatment of those diseases in which oxidative stress plays a definitive role in the pathogenesis.

Dietary Phytochemicals as Neurotherapeutics for Autism Spectrum Disorder: Plausible Mechanism and Evidence.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with symptoms ranging from lack of social interaction and communication deficits to rigid, repetitive, and stereotypic behavior. It has also been associated with comorbidities such as anxiety, aggression, epilepsy, deficit in sensory processing, as well as ADHD (attention deficit hyperactivity disorder). Apart from several behavioral and cognitive complications arising as a result of central nervous system dysfunction, there are various physiological comorbidities such as immune system deregulation, neuroinflammation, oxidative stress, mitochondrial dysfunction, and gastrointestinal complications which can worsen existing behavioral complications. There are no available treatments for these physiological comorbidities. The prevalence of gastrointestinal complications in ASD ranges from 9% to 70% and it correlates with behaviors consistent with the autistic endophenotype indicating that these are one of the major comorbidities associated with ASD. A strong connection of gut-brain cross talk occurs as a result of gut dysbiosis responsible for excessive production of short-chain fatty acids such as propanoic acid (PPA) by abnormal gut flora in ASD patients. This worsens behavioral, neurochemical, and mitochondrial dysfunction occurring in ASD. These physiological comorbidities are responsible for the generation of free radical species that cause immune system dysfunction leading to synthesis of various pro-inflammatory cytokines and chemokines. This in turn causes activation of microglia. Dietary phytochemicals are thought to be safer and useful as an alternative neurotherapeutic moiety. These compounds provide neuroprotection by modulating signaling pathways such as Nrf2, NF-κB, MAPK pathway or Sirtuin-FoxO pathway. There has been recent evidence in scientific literature regarding the modulation of gut-brain cross talk responsible for behavioral, biochemical, and mitochondrial dysfunction as well as cellular and behavioral sensory alterations by dietary phytochemicals such as curcumin, resveratrol, naringenin, and sulforaphane. These dietary phytochemicals can be formulated in novel brain-targeted delivery systems which overcome their limitation of low oral bioavailability and short half-life leading to prolonged action. Till date, not much work has been done on the development of brain-targeted neurotherapeutics for ASD. In this chapter we discuss plausible mechanisms and evidence from our own and other scientific research for the utilization of curcumin, resveratrol, naringenin, and sulforaphane as neurotherapeutics for ASD.

A novel efficient visible-light-driven double Z-scheme PANI/Ag3PO4/CNO heterojunction photocatalyst mediated by PANI and in situ grown AgNPs

Degrading organic pollutants from semiconductor photocatalysis technology is an attractive alternative to other advanced oxidation technologies, thanks to its green energy characteristics, mild reaction conditions, freedom from secondary pollution and ability to produce rich free radical species. Herein, we demonstrate the efficient degradation of several organic dyes and their mixture, which is achieved over a double Z-scheme PANI/Ag3PO4/g-C3N4-O (CNO) heterojunction catalyst and driven by visible light. With this degradation, the apparent degradation rate for RhB was up to 0.2668 min−1, which was approximately 1.31, 2.68, 5.28 and 17.12 times faster than those of PANI/Ag3PO4, Ag3PO4/CNO, Ag3PO4 and CNO, respectively. It also exhibited excellent activity for mixed dyes. Furthermore, the double Z-scheme heterojunction photocatalytic system built around Ag3PO4, which was presented and confirmed by researching the band structures of the three semiconductors and conducting radical scavenging experiments, greatly accelerates the transfer of photogenerated electrons on the conduction band of Ag3PO4; thereinto, both PANI and in situ grown AgNPs act as electron mediators, thereby improving the activity and stability of Ag3PO4. This work puts forward a novel perspective for heightening the activity and stability of perishable photocatalysts for organic dye effluent and other organic pollutant treatments.

Antimicrobial Activity of Chamomile Essential Oil: Effect of Different Formulations.

Essential oils (EOs) are highly lipophilic, which makes the measurement of their biological action difficult in an aqueous environment. We formulated a Pickering nanoemulsion of chamomile EO (CPe). Surface-modified Stöber silica nanoparticles (20 nm) were prepared and used as a stabilizing agent of CPe. The antimicrobial activity of CPe was compared with that of emulsion stabilized with Tween 80 (CT80) and ethanolic solution (CEt). The antimicrobial effects were assessed by their minimum inhibitory concentration (MIC90) and minimum effective (MEC10) concentrations. Besides growth inhibition (CFU/mL), the metabolic activity and viability of Gram-positive and Gram-negative bacteria as well as Candida species, in addition to the generation of oxygen free radical species (ROS), were studied. We followed the killing activity of CPe and analyzed the efficiency of the EO delivery for examined formulations by using unilamellar liposomes as a cellular model. CPe showed significantly higher antibacterial and antifungal activities than CT80 and CEt. Chamomile EOs generated superoxide anion and peroxide related oxidative stress which might be the major mode of action of Ch essential oil. We could also demonstrate that CPe was the most effective in donation of the active EO components when compared with CT80 and CEt. Our data suggest that CPe formulation is useful in the fight against microbial infections.

A Nitrogen- and Self-Doped Titania Coating Enables the On-Demand Release of Free Radical Species.

For potential applications such as suppressing the onset of peri-implant infections, a doped titania coating was developed to induce free radical release because of its ability for microbial elimination. The coatability of the sol–gel precursor is robust since the suspension’s rheology can be modified to attain uniform and complete surface coverage. The coating is composed of a mixture of anatase and rutile polymorphs doped with nitrogen (N3–), and it contains substoichiometric Ti2+ and Ti3+ species. Nitrogen doping results in a 0.4 eV band gap shift, while the defects induce photocurrent generation under visible light excitation up to 650 nm. Greater currents were observed in the nitrogen-doped titania at wavelengths above 450 nm vis-à-vis its (singularly) self-doped counterparts. The (photo)electrochemical behavior and photoactivity of the coating were evaluated by assessing redox species formation in a background aqueous solution. In the absence of any illumination, the coating behaved as an insulator and inhibited the activities of both oxidative and reductive species. On the other hand, under illumination, the coating enhances oxidation processes and inhibits reduction reactions within a near-field region wherein release of free radicals occurs and is constrained (delimited).

Evaluating the Efficacy of the Treatment with Benfotiamine and Alpha-lipoic Acid in Distal Symmetric Painful Diabetic Polyneuropathy

Distal symmetric painful diabetic neuropathy is the most frequent clinical form of diabetic neuropathy. The condition appears as a result of alteration of the structure and function of nervous fibres as a consequence of hyperglycaemia. Hyperglycaemia determines the metabolism of glucose on alterative pathways and generates increased oxidative stress, mechanisms that cause an accelerated apoptosis of the neurons and a high intensity of lipid peroxidation. Pathogenic treatment of diabetic neuropathy includes limited options, two of them are: Benfotiamine (inhibits the metabolism of glucose on hexosamine pathway, reducing the formation of advanced glycosylation end products) and alpha-lipoic acid (has a scavenger effect on free radical species). The study included 120 patients with distal symmetric painful diabetic neuropathy randomized in 3 treatment groups. We evaluated the effect of oral administration for 8 weeks of Benfotiamine in a dosage of 300mg/day in monotherapy, of alpha-lipoic acid in a dosage of 600 mg/day in monotherapy, respectively of both -in combined therapy - on the parameters that are used to determine the severity of distal symmetric painful diabetic neuropathy: Diabetic Neuropathy Symptoms score, Neuropathy Disability Score and the intensity of lower limb pain on the visual analogue pain scale. All the three therapies were effective with a statistically significant improvement of these parameters, but the combined therapy with alpha-lipoic acid and Benfotiamine was superior to the monotherapy with alpha-lipoic acid or Benfotiamine.

Ultrasmall platinum nanoparticles enable deep tumor penetration and synergistic therapeutic abilities through free radical species-assisted catalysis to combat cancer multidrug resistance

Despite the significant advancements in the development of a wide-variety of nanocarriers-based delivery systems for cancer therapy, several predominant issues remain unaddressed such as active combat of cancer multidrug resistance (MDR) and the limited penetration efficacy of the delivery systems. To address these issues, herein, we demonstrate the fabrication of a versatile nanoformulation by conveniently wrapping the ultrasmall platinum (Pt) nanoparticles-dispersed chitosan (CS) over the zinc-doped mesoporous silica nanocarriers (Zn-MSNs) through a facile, yet efficient self-assembly approach. These versatile nanocomposites decorated with highly active, ultrasmall Pt nanoparticles potentially facilitate the advanced therapeutic abilities of deep tumor penetration and aphotic (dark) synergistic ablation of the MDR tumors effectively. In this framework, pericellular actin staining results confirmed the effect of decorated Pt species on the integrity of the adherens junctions between cells. Remarkably, the Zn species that are doped in the siliceous frameworks substantially enhanced the loading efficiency of doxorubicin (Dox) molecules without any additional functionalization and facilitated the augmented anticancer efficacy by delivering them precisely in the tumor’s acidic microenvironment through specifically dismantling the established coordination interactions between the host and guest species. Further, the resultant free radical species from the delivered Dox species intracellularly enabled the catalytic conversion of the Pt nanoparticles to their corresponding divalent ionic species, which synergistically participated in the tumor ablation. These consequences of Pt species toward synergistic ablation of MDR cells happened to be favourable only in the presence of Dox species, a free radical generator. In vitro and in vivo investigations confirm augmented antiproliferation and synergistic inhibition effects of designed nanocomposites in the MDR tumors. These nanocomposites decorated with highly active Pt nanoparticles potentially allow for deep tumor penetration and synergistic ablation of the tumor by conveniently combating the MDR efficaciously.

Sumac (Rhus coriaria) for the prevention and treatment of necrotizing enterocolitis.

Leukotrienes, free oxygen radicals, tumor necrosis factor-alpha, and inflammatory mediators play major roles in the development of necrotizing enterocolitis (NEC). Rhus coriaria (RC: sumac) extracts may enhance cell viability by reinforcing defenses against free radical species in several progressive diseases as well as inflammatory diseases. The aim of the present study was to evaluate the effects of RC in a rat NEC model in terms of intestinal damage. Newborn pups were separated into three groups: control, NEC, and NEC treated with RC. Mortality and clinical sickness scores were evaluated. At the end of the study, ileum and proximal colon were obtained from all rats and histopathological and immunohistochemical studies were performed. In this study, the anti-inflammatory, antioxidant, immunomodulatory, and anti-apoptotic activities of RC were demonstrated in a rat NEC model, which suggests RC as a promising treatment option for preventing intestinal tissue damage. PRACTICAL APPLICATIONS: Free oxygen radicals, tumor necrosis factor-alpha, and inflammatory mediators play major roles in the development of NEC. Intestinal tissue damage is caused by necrosis and apoptosis as a result of intestinal inflammation and release of pro-inflammatory cytokines. Anti-inflammatory, antioxidant, immunomodulatory, and anti-apoptotic activities of RC are especially due to its phenolic compounds. In this study, the anti-inflammatory, antioxidant, immunomodulatory, and anti-apoptotic activities of RC were demonstrated in a rat NEC model. RC can suggest as a new treatment option for preventing intestinal injury.

Free Radical Imaging for Visualization of Radiation Treatment Using Dynamic Nuclear Polarization (DNP) MRI

In vivo dynamic nuclear polarization-magnetic resonance imaging (DNP-MRI) enables the anatomical distribution of free radical species to be monitored. DNP enhances the MRI signal from nuclei such as 1H by irradiating tissue at the electron paramagnetic resonance (EPR) frequency of the free radical, before applying the MRI pulse sequence, thus increasing the image intensity where free radicals are present. Low-molecular-weight, stable nitroxyl compounds, including Tempol and carbamoyl-PROXYL (CmP), are organic free radicals that show antioxidant capability, and they have been used as redox sensitive contrast agent. The reduction of the nitroxyl compounds depend on production of free radicals which may be influenced by factors such as overproduction of reactive oxygen species (ROS) after radiation treatment. In this study, we evaluated the feasibility of visualization of free radical generation in solution and redox alteration of mice liver induced by radiation treatment, assessed by DNP-MRI with Tempol and CmP as a molecular imaging probe. Free radical imaging for monitoring of redox reaction was performed with a low magnetic field using an in vivo DNP-MRI system (Keller, Japan Redox Inc.). DNP-MRI image of phantom including Tempol or CmP and glutathion (GSH) as reductants was obtained before and after radiation treatment (0, 5, 10, 20 Gy). Quantification of Tempol and CmP radical was performed by electron paramagnetic resonance (EPR) spectroscopy. Pharmacokinetic DNP-MRI images of liver homogenate or mitochondrial solution with or without radiation (10 or 20 Gy) were obtained at 3, 5, 10, 15, 20, 25, 30, 35 and 40 min after addition of redox probes (1mM Tempol or CmP). The redox map was obtained by the slope of the enhanced DNP image intensity of each pixel from four pharmacokinetic images using a custom Excel macro program. Direct redox reaction between 0.3mM Tempol and 10 mM GSH was observed by EPR experiments. Therefore, we determined that 1mM GSH is suitable concentration for monitoring the redox reaction by radiation treatment. DNP-MRI clearly visualized the reduction of Tempol free radical. The DNP images clearly showed the significant enhancement in tissue homogenate and mitochondrial solution. The enhancement of DNP image was gradually reduced by liver homogenate solution due to reduction of Tempol and the reduction rate of Tempol was increased by the treatment of radiation. Interestingly, reduction of Tempol in both homogenates with or without radiation were completely inhibited by KCN treatment. It is suggested that enhancement of Tempol reduction is related in mitochondrial electron transfer system. We demonstrated that the visualization of ROS production by radiation treatment and mitochondrial redox metabolic change in the electron transfer chain using DNP-MRI.

Myeloperoxidase-mediated oxidation of edaravone produces an apparent non-toxic free radical metabolite and modulates hydrogen peroxide-mediated cytotoxicity in HL-60 cells

Edaravone is considered to be a potent antioxidant drug known to scavenge free radical species and prevent free radical-induced lipid peroxidation. In this study, we investigated the effect of edaravone on the myeloperoxidase (MPO) activity, an enzyme responsible for the production of an array of neutrophil-derived oxidants that can cause cellular damage. The addition of edaravone to the reaction of MPO and hydrogen peroxide (H2O2) significantly enhanced the reduction of MPO Compound II back to native MPO. Interestingly, the MPO-mediated production of toxic hypochlorous acid exhibited a concentration-dependent biphasic effect, with the apparent optimal edaravone concentration at 10 μM. Oxidation of edaravone by MPO was examined by various analytical methods. An MPO-catalyzed product(s) of edaravone was identified at 350 nm by kinetic analysis of UV–Vis spectroscopy. Several MPO-catalyzed metabolites of edaravone were proposed from the LC-MS analyses, including oxidized dimers from edaravone radicals. Electron spin resonance (ESR) spin trapping detected a carbon-centred radical metabolite of edaravone. NMR studies revealed that there are two exchangeable hydrogens, one of which is on the α-carbon, justifying the carbon-centred edaravone radical produced from MPO. Despite the formation of an edaravone carbon-radical metabolite, it did not appear to effectively oxidize GSH (in comparison with phenoxyl radicals). Viability (ATP) and cytotoxicity (LDH release) assays showed a concentration-dependent effect of edaravone on HL-60 cells treated with either a bolus concentration of 30 μM H2O2 or a flux of H2O2 generated by 5 mM glucose and 10 mU/mL glucose oxidase. The H2O2-induced toxicity was ameliorated at high edaravone concentrations (100–200 μM). In contrast, low concentrations of edaravone (1–10 μM) exacerbated the H2O2-induced toxicity. However, the effect of edaravone at low concentration (0–10 μM) appeared more prominent with the LDH assay only. The cellular findings correlated with the biochemical studies with respect to hypochlorous acid formation. These findings provide interesting perspectives regarding the duality of edaravone as an antioxidant drug.

Direct Observation of Photochemical Free Radical Production from the Sunscreen 2‐Phenylbenzimidazole‐5‐Sulfonic Acid via Laser‐Interfaced Mass Spectrometry

AbstractThe common sunscreen molecule 2‐phenylbenzimidazole‐5‐sulfonic acid (PBSA) is studied in its gas‐phase deprotonated form ([PBSA‐H]−) for the first time as an important step in achieving a better understanding of its behavior as a photosensitizer. UV laser‐interfaced mass spectrometry is employed, revealing that [PBSA‐H]− photofragments into three ionic products (m/z 208, 193, and 80) with distinctive wavelength‐dependent production profiles. Both the m/z 208 and 80 channels produce associated neutral free radical species. Collision‐induced dissociation is performed on [PBSA‐H]−, showing that its hot ground‐state dissociates only into m/z 193 (statistical fragment). Therefore, the m/z 208 and 80 fragments which are produced strongly through the UVA/UVB are characterized as non‐statistical photofragments associated with non‐ergodic excited‐state decay. Our observation of non‐statistical photofragments reveal that [PBSA‐H]− is not behaving as a model sunscreen molecule. Further, our results indicate that the T1 state, associated with photosensitization, decays with direct free radical production.

3D Bombax-structured carbon nanotube sponge coupling with Ag3PO4 for tetracycline degradation under ultrasound and visible light irradiation

A novel photocatalytic carbon nanotube sponge with three-dimensional Bombax-structure was fabricated by a facile chemical vapor deposition followed by in situ ion-exchange approach. The as-prepared sponge achieved both high-efficiency adsorption and photocatalysis towards antibiotics, which can remove up to 90% of tetracycline within an hour. The morphology and mechanism of the photocatalytic CNT sponge were explored by multiple measures. Results show the functional groups and high specific surface area of CNT sponge play vital roles in preparing this Bombax-structured Ag3PO4/CNT sponge, the band gap of which can be tuned by varying the ration between Ag3PO4 and CNT. The photodegradation experiments of tetracycline with the assistance of ultrasound irradiation were performed, Ag3PO4/CNT sponge exhibits preferable photocatalytic activity, which can be attributed to both the enhancement of specific surface area of Ag3PO4 and the cavitation effect on CNT surface. The efficiency contributed by ultrasound could account for more than half of the degradation efficiency when the ultrasound power was 100 W. The improvement in transfer efficiency and the delay in charge recombination of Ag3PO4/CNT sponge were further verified by Electrochemical impedance spectra (EIS) and Photoluminescence tests (PL). Reactive free-radical species were detected by the Electron Spin Resonance (ESR). The intermediates and possible pathway were analyzed by gas chromatography-mass spectrometer (GC–MS) technique.

Mechanically Initiated Bulk-Scale Free-Radical Polymerization.

Mechanical initiation of polymerization offers the chance to generate polymers in new environments using an energy source with unique capabilities. Recently, a renewed interest in mechanically controlled polymerization has yielded many techniques for controlled radical polymerization by ultrasound. However, other types of polymerizations induced by mechanical activation are rare, especially for generating high-molecular-weight polymers. Herein is an example of using piezoelectric ZnO nanoparticles to generate free-radical species that initiate chain-growth polymerization and polymer crosslinking. The fast generation of high amounts of reactive radicals enable the formation of polymer/gel by ultrasound activation. This chemistry can be used to harness mechanical energy for constructive purposes in polymeric materials and for controlled polymerizations for bulk-scale reactions.

Template-free microspheres decorated with Cu-Fe-NLDH for catalytic removal of gentamicin in heterogeneous electro-Fenton process

Nano-layered double hydroxide (NLDH) decorated with Fe and Cu was applied as a novel heterogeneous catalyst for catalytic degradation of gentamicin by the electro-Fenton (EF) process. The EF process was equipped with graphite plate under aeration to electrochemically generate hydrogen peroxide in the solution. The characterization analyses confirmed the suitable structure of as-synthesized Cu-Fe-NLDH to be acted as catalyst for treating the target pollutant. The comparative study showed the highest removal efficiency of 91.3% when the Cu-Fe-NLDH-equipped EF process was applied in comparison with the Fenton (50%) and the electro-oxidation alone (25.6%). The acidic pHs favored the degradation of gentamicin. Increasing the current resulted in the enhanced degradation of gentamicin, while the excessive electrolyte concentration (0.1 mol/L) and catalyst dosage (1.5 g/L) led to the tangible drop in the reactor performance. At a specified reaction time, the injection of O3 gas enhanced the efficiency of the Cu-Fe-NLDH-equipped EF process. The presence of ethanol led to more suppressing effect than benzoquinone, indicating the dominant role of OH radical in the degradation of gentamicin compared with other free radical species such as O2- radical. Only 10% drop in the degradation efficiency of gentamicin was observed within 10 operational runs. The mineralization efficiency of about 77% was achieved after 300 min in terms of chemical oxygen demand (COD) removal. The intermediate byproducts generated during the destructive removal of gentamicin were also identified.

Up-regulation of HIF-1α is associated with neuroprotective effects of agmatine against rotenone-induced toxicity in differentiated SH-SY5Y cells.

Agmatine, a metabolite generated by arginine decarboxylation, has been reported as neuromodulator and neuroactive substance. Several findings suggest that agmatine displays neuroprotective effects in several models of neurodegenerative disorders, such as Parkinson's disease (PD). It has been hypothesized that biogenic amines may be involved in neuroprotection by scavenging oxygen radicals, thus preventing the generation of oxidative stress. Mitochondrial dysfunction, that leads to a reduction of oxygen consumption, followed by activation of prolyl hydroxylase and decrease of hypoxia-inducible factor 1 alpha (HIF-1α) levels, has been demonstrated to play a role in PD pathogenesis. Using rotenone-treated differentiated SH-SY5Y cells as the in vitro PD model, we here investigated the molecular mechanisms underlying agmatine neuroprotective effects. Our results showed that the preliminary addition of agmatine induces HIF-1α activation, and prevents the rotenone-induced production of free radical species, and the activation of apoptotic pathways by inhibiting mitochondrial membrane potential decrease and caspase 3 as well as cytochrome c increase. Notably, these effects are mediated by HIF-1α, as indicated by experiments using a HIF-1α inhibitor. The present findings suggest that the treatment with agmatine is able to counteract the neuronal cell injury evoked by mitochondrial toxins.

Study of Influence of Free Radical Species on Antioxidant Activity of Selected 1,2,4‐Triazole‐3‐thiones

AbstractThe free radical scavenging potency of four 1,2,4‐triazole‐3‐thione compounds towards ten chosen radicals was investigated. The thermodynamic parameters, Gibbs free energies of reactions and reaction enthalpies, were used to determine the most probable mechanism of action. The results indicated that the favourable mechanism of antiradical action was dependent both on the polarity of solvents and a nature of free radical species. The results suggested that Sequential Proton Loss Electron Transfer (SPLET) is the most probable for reaction in benzene, while Hydrogen Atom Transfer (HAT) was favorized for reaction occurring in methanol. The constant competition between these mechanisms of antioxidative action was present. The molecular docking study, obtained for parent molecules of chosen 1,2,4‐triazole‐3‐thiones compounds and their corresponding anionic species, showed their inhibitory nature against histidine kinase inhibitor Sda. Except in the case of compound 4 a, all the anionic species (4 d‐4 h) showed the lower inhibition constants, indicating better inhibition potency of Sda, than corresponding parent molecules.

Formation of methyl radicals derived from cumene hydroperoxide in reconstructed human epidermis: an EPR spin trapping confirmation by using 13C-substitution

Dermal exposure to cumene hydroperoxide (CumOOH) during manufacturing processes is a toxicological issue for the industry. Its genotoxicity, mutagenic action, ability to promote skin tumour, capacity to induce epidermal hyperplasia, and aptitude to induce allergic and irritant skin contact dermatitis are well known. These toxic effects appear to be mediated through the activation to free radical species such as hydroxyl, alkoxyl, and alkyl radicals characterised basically by electron paramagnetic resonance (EPR) and spin-trapping (ST) techniques. To be a skin sensitiser CumOOH needs to covalently bind to skin proteins in the epidermis to form the antigenic entity triggering the immunotoxic reaction. Cleavage of the O–O bond allows formation of unstable CumO•/CumOO• radicals rearranging to longer half-life specific carbon-centred radicals R• proposed to be at the origin of the antigen formation. Nevertheless, it is not still clear which R• is precisely formed in the epidermis and thus involved in the sensitisation process. The aim of this work was to elucidate in conditions closer to real-life sensitisation which specific R• are formed in a 3D reconstructed human epidermis (RHE) model by using 13C-substituted CumOOH at carbon positions precursors of potentially reactive radicals and EPR-ST. We demonstrated that most probably methyl radicals derived from β-scission of CumO• radicals occur in RHE through a one-electron reductive pathway suggesting that these could be involved in the antigen formation inducing skin sensitisation. We also describe a coupling between nitroxide radicals and β position 13C atoms that could be of an added value to the very few examples existing for the coupling of radicals with 13C atoms.