Superoxide Dismutase Mimetic Activity Research Articles

Tungsten-rosmarinic acid nanoenzyme with SOD mimetic activity for the treatment of psoriasis by eliminating ROS and relieving inflammation

Psoriasis is a refractory skin disease that seriously affects the physical and mental health of patients. It is easy to relapse and cannot be cured, which seriously harms the physical and mental health of patients. Oxidative stress, driven by increased reactive oxygen species (ROS), plays a critical role in excessive keratinocyte proliferation and local inflammation in psoriasis. In this study, we successfully synthesized a tungsten-rosmarinic acid nanoenzyme (WRA-PEG), which demonstrates promising therapeutic potential for psoriasis. Our findings demonstrate that WRA-PEG effectively scavenges ROS, reduces the proliferation of keratinocytes, and mitigates the release of pro-inflammatory cytokines in vitro. In a psoriasis-like mouse model induced by imiquimod (IMQ), WRA-PEG significantly improved clinical manifestations and prevented recurrence, as evidenced by reduced epidermal thickness and inhibited inflammatory cytokine expression, outperforming traditional treatments like Benvitimod. Bioinformatics analysis revealed the modulation of key inflammatory and oxidative stress-related pathways, highlighting the involvement of crucial genes such as CCL20 and TNFSF10 in its mechanism of action. Furthermore, WRA-PEG exhibited excellent biocompatibility and stability without adverse effects on liver or kidney function. These results underscore the potential of WRA-PEG as a novel therapeutic strategy for managing psoriasis.

Recombinant Human Heavy Chain Ferritin Nanoparticles Serve as ROS Scavengers for the Treatment of Ischemic Stroke.

Ischemic stroke is a high-incidence disease that threatens human well-being. The potent neuroprotective effects render reactive oxygen species (ROS) scavengers potential agents for acute ischemic stroke therapy. Challenges such as inadequate permeability across the blood-brain barrier (BBB), limited half-life, and adverse effects hinder the widespread utilization of small molecule and inorganic ROS scavengers. Thus, there is an urgent demand for efficacious neuroprotective agents targeting ischemic stroke. Our study discovered the superoxide dismutase (SOD)-mimetic activity of recombinant human heavy chain ferritin (rHF) nanoparticles expressed from Escherichia coli (E. coli). Subsequent investigations delved into the ROS-scavenging proficiency of rHF within neural cells, its therapeutic efficacy against ischemic stroke, and the elucidation of its neuroprotective mechanisms. rHF protein nanoparticles were expressed in E. coli and purified via size-exclusion chromatography. The superoxide anion (•O2-) scavenging SOD-mimetic activity of rHF nanoparticles was measured using a SOD detection kit. The ROS scavenging ability and protection effects against oxidative damage of rHF nanoparticles were studied in H2O2-induced PC12 cells. Therapeutic effects and neuroprotective mechanisms of rHF against ischemic stroke were investigated with transient middle cerebral artery occlusion (MCAO) reperfusion mice model. rHF nanoparticles can eliminate excessive ROS in nerve cells and alleviate oxidative damage. The results of animal experiments demonstrated that rHF nanoparticles passed across BBB, reduced infarct areas in brain tissue, and lowered the neurological deficit score of ischemia-reperfusion model mice. Additionally, rHF nanoparticles mitigated neuronal apoptosis and ferroptosis, suppressed microglial activation, maintained oxygen homeostasis, and exhibited negligible organ toxicity. rHF nanoparticle could be developed as a new ROS scavenger for nerve cells and has therapeutic potential as a drug for cerebral ischemia-reperfusion injury.

Multifunctional bimetallic MOF with oxygen vacancy synthesized by microplasma for rapid total antioxidant capacity assessment in agricultural products

The assessment of total antioxidant capacity (TAC) is crucial for evaluating overall antioxidant potential, predicting the risk of chronic diseases, guiding dietary and nutritional interventions, and studying the effectiveness of antioxidants. However, achieving rapid TAC assessment with high sensitivity and stability remains a challenge. In this study, Ce/Fe-MOF with abundant oxygen vacancies was synthesized using microplasma for TAC determination. The microplasma synthesis method was rapid (30 min) and cost-effective. The presence of oxygen vacancies and the collaboration between iron and cerium in Ce/Fe-MOF not only enhanced the catalyst's efficiency but also conferred multiple enzyme-like properties: peroxidase-like, oxidase-like, and superoxide dismutase mimetic activities. Consequently, a simple colorimetric assay was established for TAC determination in vegetables and fruits, featuring a short analysis time of 15 min, a good linear range of 5–60 μM, a low detection limit of 1.3 μM and a good recovery of 91 %-107 %. This method holds promise for rapid TAC assessment in agricultural products.

Investigating temperature variability on antioxidative behavior of synthesized cerium oxide nanoparticle for potential biomedical application.

Cerium oxide nanoparticles (CNP) have garnered significant attention due to their versatile redox properties and wound-healing applications. The antioxidative nature of CNP is due to its ability to be oxidized and reduced, followed by the capture or release of oxygen which is used for scavenging reactive oxygen species (ROS). Herein, CNP is produced through a wet chemistry approach and its tunable redox property is tested across a range of temperatures. The synthesized CNP was observed to reveal the signature peak at 245nm indicating a high Ce+3/Ce+4 ratio. Towards evaluating the redox antioxidative behavior, CNPs were subjected to a comprehensive analysis for superoxide dismutase mimetic analysis with riboflavin-mediated nitroblue tetrazolium scavenging assay. The results demonstrated that the redox activity of cerium oxide nanoparticles was strongly influenced by the different temperature ranges. Superoxide dismutase mimetic activity was observed to be reduced with a decrease in temperature as we moved from 4°C (80% activity) to -80°C (47% activity) at 1mM conc of CNP. Similarly, the SOD mimetic activity increased with an increase in temperature from 40°C (72% activity) to 70°C (94% activity). Further, CNP was found to inhibit E. coli (gram+ve) and Enterobacter (gram-ve) beyond 70% simultaneously at 1mM conc, indicating its potential application as a remarkable antimicrobial agent. CNP also inhibited the alpha-amylase activity up to the 60% at 1mM conc suggesting its potential application in antidiabetic wound healing therapy. Overall, the CNP finds its application in mitigating the oxidative stress-related disorder exhibited by its high antioxidative, antimicrobial, and antidiabetic behavior.

Synthesis and characterization of nano crystallite carboxamide-based iron(III) complexes: SOD mimetic activity, antibacterial and anticancer activity and molecular docking study

Three carboxamide-based ligands and their iron(III) complexes were prepared and structurally characterized. Analytical, thermal and mass spectra measurements showed a 1:1 stoichiometric (M:L) of the synthesized iron(III) complexes. The distorted octahedral geometry of the present iron(III) complexes was assigned based on the results of spectroscopy and magnetometry. Processing of X-ray diffraction data for powder samples by the software Expo 2014 confirmed the octahedral geometry of the three iron(III) complexes. Electrochemical properties of the present iron(III) complexes were studied by cyclic voltammetric measurements. The present iron(III) complexes exhibit SOD like activity with IC50 values of 16.45, 15.24 and 9.70 μM. The drive forces (−λ or ΔG°) controlling these biocatalytic reactions were determined and correlated with catalytic activity. The proposed catalytic mechanistic implications for the conversion of O2 •− to H2O2 and H2O were discussed. The antimicrobial activity has been studied in vitro against G(+) and G(−) pathogenic bacteria. The in vitro anticancer activity of the carboxamide-based ligands and their iron(III) complexes against human Hepatocellular carcinoma (HepG-2) cell lines was examined. The obtained results demonstrated the potent anticancer activity of iron(III) complexes with increased safety on normal cells compared to cisplatin. Molecular docking calculations confirmed the experimental findings of the antibacterial and anticancer activities of both free ligands and their iron(III) chelates. Communicated by Ramaswamy H. Sarma

Self-assembled hemin-conjugated heparin with dual-enzymatic cascade reaction activities for acute kidney injury

Nanozymes have prominent catalytic activities with high stability as a substitute for unstable and expensive natural enzymes. However, most nanozymes are metal/inorganic nanomaterials, facing difficulty in clinical translation due to their unproven biosafety and limited biodegradability issues. Hemin, an organometallic porphyrin, was newly found to possess superoxide dismutase (SOD) mimetic activity along with previously known catalase (CAT) mimetic activity. However, hemin has poor bioavailability due to its low water solubility. Therefore, a highly biocompatible and biodegradable organic-based nanozyme system with SOD/CAT mimetic cascade reaction activity was developed by conjugating hemin to heparin (HepH) or chitosan (CS-H). Between them, Hep-H formed a smaller (<50 nm) and more stable self-assembled nanostructure and even possessed much higher and more stable SOD and CAT activities as well as the cascade reaction activity compared to CS-H and free hemin. Hep-H also showed a better cell protection effect against reactive oxygen species (ROS) compared to CS-H and hemin in vitro. Furthermore, Hep-H was selectively delivered to the injured kidney upon intravenous administration at the analysis time point (24 h) and exhibited excellent therapeutic effects on an acute kidney injury model by efficiently removing ROS, reducing inflammation, and minimizing structural and functional damage to the kidney.

Binuclear Cu(II), Ni(II) and Zn(II) complexes of hydrazone Schiff bases: Synthesis, spectroscopy, DFT calculations, and SOD mimetic activity

Two new salicylaldimine-based N-heterocyclic hydrazone ligands, N'-[(2-hydroxyphenyl) methylene]-2-(2-phenyl-1H-benzimidazol-1-yl)acetohydrazone (H2L1) and 2-[2-(3-chlorobenzyl)-1H-benzimidazol-1-yl]-N'-[(2-(hydroxyimino)-1-ethylpropylidene]aceto hydrazone (H2L2) and their homo-binuclear nickel(II), copper(II) and zinc(II) complexes have been synthesized and their structures were identified by using spectroscopic techniques and elemental analysis. The two ligands in both the solid state and solution state show tautomerism, but their complexes don't show tautomerism due to the deprotonation and metal ion(s) binding the ligand in the enol-imine-enol form. The stoichiometries of the complexes were also confirmed by thermal analysis with formation of the corresponding metal oxides. TD-DFT calculations have also been performed to correlate geometrical parameters with the spectral properties of compounds and to assign vibrations and electronic transitions. Evaluations of the mimetic catalytic activities of the complexes for the superoxide dismutase (SOD) enzyme were also performed through in vitro tests. All of the complexes studied exhibit activity and the Cu(II) complex (3b) shows the highest activity with the lowest IC50 value (2.50 ± 0.60 µM).

Phenolic Profiles, Antioxidant and Anti-Inflammatory Activities of Hydrodistillation Wastewaters from Five Lamiaceae Species.

Distillation is the most widely used method to obtain an essential oil from plant material. The biomass used in the process is returned as a solid residue together with variable amounts of water rich in water-soluble compounds, which currently are not addressed to any further application. The scope of this work was to evaluate the phytochemical composition of wastewaters coming from hydrodistillation (DWWs) of five aromatic plants belonging to the Lamiaceae family, and to assess their in vitro antioxidant and anti-inflammatory activities. The phenolic profiles of the DWWs were determined by HPLC-DAD and HPLC-ESI/MS. Free radical scavenging ability, oxygen radical antioxidant capacity and superoxide dismutase mimetic activity of the samples under study were measured. Moreover, to investigate the anti-inflammatory activity of the DWWs, an in vitro experimental model of intestinal inflammation was used. The DWW samples' phytochemical analysis allowed the identification of 37 phenolic compounds, all exhibiting good antioxidant and anti-inflammatory activity. Our study contributes to the knowledge on the polyphenolic composition of the DWWs of five aromatic plants of the Lamiaceae family. The results highlight the presence of compounds with proven biological activity, and therefore of great interest in the pharmaceutical and nutraceutical fields.

THE CERIUM OXIDE GENERATED RADICAL ELIMINATION PROPERTIES OF PEG-NANOCERIA

Reactive oxygen species (ROS) have been linked to cellular degeneration, irreversible DNA damage, and various diseases. Cerium oxide nanoparticles have shown promising medical applications for their SOD mimetic activity to catalyze the breakdown of various ROS. Increasing the biocompatibility, longevity of residence, and rate of internalization of nanoceria are essential to increase its range of biomedical applications. Polyethylene glycol’s (PEG) hydrophilic, nonimmunogenic, and antioxidative properties make it an ideal coating for increasing cerium nanoparticle’s applicability. Gelatin’s low cost and versatility have made it widely employed as an antioxidant drug carrier in a variety of physiological systems. Because of gelatin’s susceptibility to ROS denaturation and well-researched structure, it is a useful tool for assessing conformational damage in applications that involve acute oxidative stress. PEG-nanoceria of various molar weights was synthesized from Ce (III) nitrate and incorporated into gelatin hydrogels that were exposed to hydrogen peroxide to provide oxidative stress damage. This study aims to assess changes to gelatin conformation were assessed using Fourier transform infrared spectroscopy. PEGNanoceria showed radical damage mitigation in hydrogels as evident by the decreased change in transmittance over its nonPEG counterpart. There was notably exceptional damage mitigation in the amide A and amide II regions. These promising findings suggest more research should be done to examine polymer-coated nanoceria’s antioxidative properties in more biologically relevant models.

New Cu+2 Complexes with N-Sulfonamide Ligands: Potential Antitumor, Antibacterial, and Antioxidant Agents.

Nowadays, the discovery of a new non-toxic metal complex with biological activity represents a very active area of research. Two Cu+2 complexes, [Cu(L1)2(H2O)3] (C1) (HL1= N-(5-(4-methylphenyl)-[1,3,4]–thiadiazole–2-yl)-naphtalenesulfonamide) and [Cu(L2)2(py)2(H2O)] (C2) (HL2= N-(5-ethyl-[1,3,4]–thiadiazole–2-yl)-naphtalenesulfonamide), with two new ligands were synthesized. The X-ray crystal structures of the complexes were determined. In both complexes, Cu+2 is five-coordinated, forming a CuN2O3 and CuN4O chromophore, respectively. The ligands act as monodentate, coordinating the metal ion through a single Nthiadiazole atom; for the C2 complex, the molecules from the reaction medium (pyridine and water) are also involved in the coordination of Cu+2. The complexes have a distorted square pyramidal square-planar geometry. The compounds were characterized by FT-IR, electronic EPR spectroscopy, and magnetic methods. The nuclease activity studies confirm the complexes’ capacity to cleave the DNA molecule. Using a xanthine-xanthine oxydase system, the SOD mimetic activity of the complexes was demonstrated. Cytotoxicity studies were carried out on two tumor cell lines (HeLa, WM35) and on a normal cell line (HFL1) using the MTT method, with cisplatin used as a positive control. The antibacterial activity of the complexes was investigated against two Gram-positive and two Gram-negative bacteria, and compared with Amoxicillin and Norfloxacin using the disk diffusion method. Both complexes showed in vitro biological activity but the C2 complex was more active. A lack of in vivo toxicity was demonstrated for the C2 complex by performing hepatic, renal, and hematological studies on Swiss mice.

Mono- and binuclear copper(II) complexes with different structural motifs and geometries: Synthesis, spectral characterization, DFT calculations and superoxide dismutase enzymatic activity

Several new copper(II) mono- and binuclear complexes, [Cu(HL)(ClO4)(H2O)]CH3OH (1), [Cu(HL)(DMF)](ClO4)CH3OH (2), [Cu2(HL)2(pyrazine)](ClO4)2(3) and [Cu2(HL)2(4,4-bipy)(ClO4)2]2H2O (4) (HL = 4-bromo-2-(pyridine-2-ylhydrazonomethyl)-phenol, 4,4-bipy = 4,4-bipyridyl) have been synthesized and characterized by elemental analysis, FTIR, UV–vis and electron paramagnetic resonance (Epr) spectroscopy. Molecular structures of all complexes have been obtained using single crystal X-ray analysis. The geometry of copper(II) in 1 is distorted square pyramidal and distorted square planar in 2. In binuclear complexes each copper(II) centre has distorted square planar and distorted square pyramidal geometry in 3 and 4, respectively. The complexes 1–4 possess the self-assembled supramolecular structures via different molecular interactions (hydrogen bondings, CH ⋯π and π⋯π stacking interactions). The possible intermolecular interactions were explored using 3D Hirshfeld surface and related 2D fingerprint plots, spectroscopic properties were studied using UV–visible and electron paramagnetic resonance techniques. Optimized geometry, frontier molecular orbital (FMO) and natural bond order (NBO) analysis were performed using density functional theory (DFT) calculations. To predict the chemical reactivity of complexes some global reactivity descriptors (chemical potential μ, electronegativity χ, hardness η and electrophilicity index ω) have been evaluated using DFT. The low temperature magnetic susceptibility measurements of binuclear complexes have been obtained predicts the magnetic exchange coupling value (J) by variable temperature measurements. The magnetic exchange coupling value (J) obtained are −8.1 and −2.4 cm−1 for 3 and 4, respectively. The superoxide dismutases (SOD) of all complexes were measured using NBT assay method. The complexes show moderate superoxide dismutase (SOD) mimetic activity.

Copper hydrazone complexes with different nuclearties and geometries: Synthesis, characterization, single crystal structures, Hirshfeld analysis and superoxide dismutase mimetic activities

Three new copper(II) hydrazone complexes [Cu(L)(neocuproine)]NO31, [Cu(L)(6-benzylaminopurine)ClO4] 2 and [Cu(L)μ(1,1-N3)Na(H2O)2] 3 with different nuclearties and geometries using acetic acid(2‑hydroxy-3‑methoxy-benzylidene)-hydrazide (HL) as proligand and neucuproine, 6-benzylaminopurine and sodium azide as co-ligands have been synthesized and characterized using several physico-chemical and spectral methods. Molecular structures of complexes were obtained by single crystal diffraction technique. The coordination sphere in complexes 1 and 2 can be illustrated as distorted square pyramidal geometry whereas 3 has distorted square planar geometry. Supramolecular structures were formed via different intermolecular interactions like hydrogen bondings and CH⋯π in 1, hydrogen bondings, CH⋯π and lp⋯π in 2 and hydrogen bondings, CH⋯π, lp⋯π and π⋯π(chelate-chelate) interactions in 3. The Hirshfeld surface analysis exhibited O⋯H, N⋯H and C⋯H interactions in all complexes. The optimized geometry of newly synthesized complexes were obtained by B3LYP/LANL2DZ model. From the differences in energies of frontier molecular orbitals (ΔEg), reactivity parameters like, ionization potential (IP), electron affinity (EA), electronegativity (χ), softness (S), hardness (η) and electrophilicity index (ω) were determined. In these complexes the Epr parameters (g-) showed the trend g∥>g⊥>2.0023, which is consistent with a dx2−y2 ground state in a square based geometry. Electrochemical properties also determined using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Additionally, superoxide dismutase catalytic activity measurements were performed by nitro blue tetrazolium chloride (NBT) assay in phosphate buffer. All complexes catalyzed the dismutation of superoxide at biological pH. Enhancement in the SOD activity of 2 can be credited to the coordinated poorly bound ClO4− ion which is easily replaced by O2·− ion.

Systemic Administration of Tempol, a Superoxide Dismutase Mimetic, Augments Upper Airway Muscle Activity in Obese Zucker Rats.

Obstructive sleep apnea (OSA) is characterized by repetitive partial/complete collapse of the pharynx during sleep, which results in apnea/hypopnea leading to arterial oxygen desaturations and arousals. Repetitive apnea/hypopnea-arousal episodes cause hypoxia/reoxygenation cycles, which increase free radical generation and oxidative stress that cause motor/sensory nerve impairments and muscle damage. We hypothesize that antioxidants may protect and/or reverse from oxidative stress-induced damage in OSA patients. To understand the acute protective effects of antioxidants on respiratory muscles, we studied the systemic effects of a membrane permeable superoxide dismutase mimetic, Tempol, on genioglossus (EMGGG) and diaphragmatic (EMGDIA) electro-myographic activities, hypoglossal motoneuron (HMN) nerve activity and cardiorespiratory parameters (mean arterial blood pressure, heart rate) in adult isoflurane-anesthetized obese Zucker rats (OZR) and age-matched lean Zucker rats (LZR). Tempol dose-dependently (1–100 mg/kg) increased EMGGG without changing EMGDIA in OZR and LZR. Tempol increased respiratory rate and tidal volume in OZR and LZR. Tempol (1–25 mg/kg) dose-dependently increased HMN nerve activity in healthy Sprague Dawley rats. Tempol (100 mg/kg) increased EMGGG output by 189% in OZR and 163% in LZR. With respect to mechanisms of effect, Tempol (100 mg/kg) did not augment EMGGG after bilateral HMN transection in Sprague Dawley rats. Although future studies are warranted, available data suggest that in addition to its antioxidant and antihypertensive properties, Tempol can selectively augment EMGGG through modulating HMN and this effect may prevent collapsibility and/or improve stability of the upper airway pharyngeal dilator muscles during episodes of partial and/or complete collapse of the upper airway in OSA human subjects.

Determination of catechin and glutathione using copper aspartate nanofibers with multiple enzyme-like activities.

Copper aspartate nanofibers were facilely prepared based on aspartic acid and copper (CuAsp nanofibers). It is found that the prepared CuAsp nanofibers have catalytic activities of five enzymes, including peroxidase, laccase, catalase, ascorbate oxidase, and superoxide dismutase mimetic activities. The kinetic and catalytic properties of CuAsp nanofibers were systematically investigated, showing their high catalytic activity, excellent stability, and reusability. The laccase mimetic activity of nanofibers could be used to detect catechin in the range 20-1200µM with a detection limit of 5.88µM. In addition, a sensing platform for glutathione with a detection limit of 0.25µM and a detection range of 1-50µM was established based on CuAsp nanofibers which have the peroxidase-mimicking activity. The sensor had good selectivity and could detect glutathione in actual samples of human serum. Therefore, CuAsp nanofibers with multi-enzyme activity have broad application prospects such as biosensing, environmental management, and disease diagnosis.

The therapeutic effect of cerium oxide nanoparticle on ischaemia/reperfusion injury in rat testis

Testicular torsion is a dangerous urogenital disorder which is caused by twisting of spermatic cord, and unless immediate treatments happen at a proper time, oxidative stress, occurred during ischaemia reperfusion, finally leads to irreversible disintegration of testicular tissue. One of the first preventive lines is to administrate antioxidant factors. In the present study, we investigate the therapeutic effect of cerium oxide nanoparticle on the injury. We divided 45 rats into nine groups, subjected eight groups to testicular torsion-detorsion, injected different doses of cerium oxide nanoparticle into the peritoneum of six groups and analysed all the groups regarding spermatogenetic indices including sperm count, sperm viability and Johnson mean. Our results showed that cerium oxide nanoparticle can alleviate oxidative stress in testis, and this alleviation promotes the reproductive indices as the concentration of cerium oxide nanoparticles increases. The catalase-mimetic and superoxide dismutase-mimetic activities of cerium oxide nanoparticle are the most probable theories to explain the antioxidant effect of the nanoparticle.

High-performance SOD mimetic enzyme Au@Ce for arresting cell cycle and proliferation of acute myeloid leukemia

SOD-like activity of CeO2 nanoparticles (Ce NPs) is driven by Ce3+/Ce4+, high oxidative stress can oxidize Ce3+ to reduce the ratio of Ce3+/Ce4+, inactivating the SOD activity of Ce NPs. Herein, we found Au@Ce NPs, assembled by Au NPs and Ce NPs, exhibited high-performance of SOD mimetic enzyme activity even upon the oxidation of H2O2. Ce NPs supported by nano-Au can acquire the electrons from Au NPs through the enhanced localized surface plasmon resonance (LSPR), maintaining the stability of Ce3+/Ce4+ and SOD-like activity. Meanwhile, Au@Ce NPs retained the peroxidase function and catalase function. As a result, Au@Ce NPs effectively scavenged O2•- and the derived ROS in AML cells, which are the important signaling source that drives AML cell proliferation and accelerates cell cycle progression. When HL-60 cells were treated by Au@Ce NPs, the removal of endogenous ROS signal significantly arrested cell cycle at G1 phase and suppressed the cell proliferation by blocking the mitogen-activated protein kinases (MAPKs) signaling and the Akt/Cyclin D1 cell cycle signaling. Importantly, this treatment strategy showed therapeutic effect for subcutaneous transplantation of AML model as well as a satisfactory result in diminishing the leukocyte infiltration of liver and spleen particularly. Thus, assembled Au@Ce NPs show the high-performance SOD-like activity, promising the potential in treating AML and regulating abnormal ROS in other diseases safely and efficiently.

Engineered nanoceria modulate neutrophil oxidative response to low doses of UV-B radiation through the inhibition of reactive oxygen species production.

To avoid aging and ultraviolet mediated skin disease the cell repair machinery must work properly. Neutrophils, also known as polymorphonuclear leukocytes, are the first and most abundant cell types which infiltrate sites of irradiation and play an important role in restoring the microenvironment homeostasis. However, the infiltration of neutrophils in ultraviolet-B (UV-B) irradiated skin might also contribute to the pathophysiology of skin disease. The polymorphonuclear leukocytes activation induced by UV-B exposure may lead to prolonged, sustained NADPH oxidase activation followed by an increase in reactive oxygen species (ROS) production. Our previous work showed that cerium oxide nanoparticles can protect L929 fibroblasts from ultraviolet-B induced damage. Herein, we further our investigation of engineered cerium oxide nanoparticles (CNP) in conferring radiation protection specifically in modulation of neutrophils' oxidative response under low dose of UV-B radiation. Our data showed that even low doses of UV-B radiation activate neutrophils' oxidative response and that the antioxidant, ROS-sensitive redox activities of engineered CNPs are able to inhibit the effects of NADPH oxidase activation while conferring catalase and superoxide dismutase mimetic activity. Further, our investigations revealed similar levels of total ROS scavenging for both CNP formulations, despite substantial differences in cerium redox states and specific enzyme-mimetic reaction activity. We therefore determine that CNP activity in mitigating the effects of neutrophils' oxidative response, through the decrease of ROS and of cell damage such as chromatin condensation, suggests potential utility as a radio-protectant/therapeutic against UV-B damage.

Mononuclear copper(II) complexes with (Z)-N′-{(2-hydroxynapthalen-1-yl}methylene)acetohydrazide: X-ray single-crystal structures, Hirshfeld analysis, X-band epr spectra, DFT calculations and SOD mimetic activity

The 1:1 reaction of (Z)-Ń-{(2-hydroxynapthalen-1-yl}methylene)acetohydrazide (HL) and copper(II) salt in methanol yields a series of new mononuclear complexes, [Cu(HL)(OH2)]ClO41, [Cu(HL)(OH2]ClO42, [Cu(HL)(OH2)]NO33 and [Cu(L)(Cl)] 4. The room temperature magnetic moments of the complexes 1–4 are 1.79, 1.78, 1.80 and 1.76B.M. respectively. The absorption bands emerging in the UV region (337–341 nm) are characteristic of the HL ligand. In these complexes, the LMCT bands were observed in the range of 503–506 nm and the d-d band at 617–623 nm. The molecular structures of all four complexes have been solved using single-crystal X-ray analysis. The X-ray analysis shows the formation of supramolecular structures through various non-covalent interactions viz., CH∙∙∙π and π···π intermolecular interactions. The detailed Hirshfeld surface and fingerprint plots yielded a comparative picture of the mode of non-covalent interactions. The DFT calculations were performed and the results are in good agreement with experimental results. X-band epr spectral measurements have been carried out to authenticate the paramagnetic behavior of all complexes. The stability of the copper(II) centre was examined using cyclic and differential pulse voltammetry. The IC50 and SOD activity values for all complexes reveal that they are good models among the best values reported for low molecular weight mononuclear copper(II) complexes.

Three -(pyridin-2-yl)-2-(pyridin-2-ylimino)thiazolidin-4-one as a novel inhibitor of cerebral MAO-B activity with antioxidant properties and low toxicity potential.

Some brain diseases are associated with oxidative stress and altered monoamine oxidase (MAO) activity. The objective of this study was to evaluate the antioxidant and neuroprotective actions through MAO inhibition of 3-(pyridin-2-yl)-2-(pyridine-2-ylimino) thiazolidin-4-one (PPIT, a synthetic molecule containing a thiazolidinone nucleus), as well as its effects on toxicity parameters in Swiss female mice. Five in vitro assays were carried out to verify the PPIT antioxidant capacity: protein carbonylation (PC), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 1,1-diphenyl-2-picryl-hydrazil (DPPH), ferric ion (Fe3+ ) reducing antioxidant power (FRAP), and superoxide dismutase (SOD)-like activity. The results showed that PPIT reduced the level of PC in the homogenate of the brain. This compound did not demonstrate SOD mimetic activity, but it acted as a free radical scavenger (ABTS and DPPH) and exhibited reducing activity in the FRAP assay. In addition, the effects of PPIT on cerebral MAO activity (MAO-A and B isoforms) were investigated in vitro. Our data revealed inhibition of the MAO-B activity by PPIT with no effects on MAO-A. Lastly, an acute oral toxicity test was conducted in mice. No changes in food intake, body weight, and biochemical markers of kidney and liver damage were detected in mice treated with a high dose of PPIT (300 mg/kg). In conclusion, the present study demonstrated that PPIT exhibits antioxidant activity and selectively inhibits the MAO-B isoform without causing apparent toxicity. These findings suggest PPIT as a potential therapeutic candidate to be tested in preclinical models of brain diseases involving perturbations of MAO-B activity and redox status.

Cerium oxide nanomaterial with dual antioxidative scavenging potential: Synthesis and characterization

Many studies have linked reactive oxygen species (ROS) to various diseases. Biomedical research has therefore sought a way to control and regulate ROS produced in biological systems. In recent years, cerium oxide nanoparticles (nanoceria, CNPs) have been pursued due to their ability to act as regenerative ROS scavengers. In particular, they are shown to have either superoxide dismutase (SOD) or catalase mimetic (CAT) potential depending on the ratio of Ce3+/Ce4+ valence states. Moreover, it has been demonstrated that SOD mimetic activity can be diminished by the presence of phosphate, which can be a problem given that many biological systems operate in a phosphate-rich environment. Herein, we report a CNP formulation with both SOD and catalase mimetic activity that is preserved in a phosphate-rich media. Characterization demonstrated a highly dispersed, stable solution of uniform-sized, spherical-elliptical shaped CNP of 12 ± 2 nm, as determined through dynamic light scattering, zeta potential, and transmission electron microscopy. Mixed valence states of Ce ions were observed via UV/Visible spectroscopy and XPS (Ce3+/Ce4+ > 1) (Ce3+∼ 62%). X-ray diffraction and XPS confirmed the presence of oxygen-deficient cerium oxide (CeO2-x) particles. Finally, the CNP demonstrated very good biocompatibility and efficient reduction of hydrogen peroxide under in-vitro conditions.