Multiple Free Radical Scavenging Research Articles

In situ photocrosslinkable hydrogel treats radiation-induced skin injury by ROS elimination and inflammation regulation

The clinical management of radiation-induced skin injury (RSI) poses a significant challenge, primarily due to the acute damage caused by an overabundance of reactive oxygen species (ROS) and the ongoing inflammatory microenvironment. Here, we designed a dual-network hydrogel composed of 5 % (w/v) Pluronic F127 diacrylate and 2 % (w/v) hyaluronic acid methacryloyl, termed the FH hydrogel. To confer antioxidant and anti-inflammation properties to the hydrogel, we incorporated PVP-modified Prussian blue nanoparticles (PPBs) and resveratrol (Res) to form PHF@Res hydrogels. PHF@Res hydrogels not only exhibited multiple free radical scavenging activities (DPPH, ABTS), but also displayed multiple enzyme-like activities (POD-, catalase). Meanwhile, PHF@Res-2 hydrogels significantly suppressed intracellular ROS and promoted the migration of fibroblasts in a high-oxidative stress environment. Moreover, in the RSI mouse model, the PHF@Res-2 hydrogel regulated inflammatory factors and collagen deposition, significantly reduced epithelial hyperplasia, promoted limb regeneration and neovascularization, and accelerated wound healing, outperforming the commercial antiradiation formulation, Kangfuxin. The PHF@Res-2 hydrogel dressing shows great potential in accelerating wound healing in RSI, offering tremendous promise for clinical wound management and regeneration.

Performance Study and Application of Antioxidant Peptides CHCIWM and CHCPWM

AbstractWhen the level of reactive oxygen species (ROS) increases abnormally in the body, it damages tissue cells and is closely related to the occurrence of various chronic diseases. Antioxidant peptides (APs) are a class of active short peptides with antioxidant capacity, which have great research value. In this paper, two APs were designed and synthesized based on the structural features of APs: CHIWM (AP1) and CHCPWM (AP2). The reactive sites and activities of APs were analyzed using the quantum chemical density functional theory (DFT) method. The reactive sites are all located in the indolyl heterocycle of tryptophan residues, among which AP1 has a smaller energy gap and single point energy. Multiple free radical scavenging assays showed that AP1 and AP2 had stronger antioxidant activity than the positive control, glutathione (GSH). For scavenging DPPH free radicals, the IC50s values were 0.613 mg/mL and 0.606 mg/mL, respectively. In cellular assays, both AP1 and AP2 were able to scavenge ROS in the cells and attenuate cellular damage. In conclusion, AP1 and AP2 designed in this paper have good antioxidant activity and have the potential to be applied in the treatment of chronic diseases caused by cellular oxidative damage.

Theoretical Study on the Multiple Free Radical Scavenging Reactions of Pyranoanthocyanins.

The free radical trapping capacities of multiple pyranoanthocyanins in wine storage and ageing were theoretically explored by density functional theory (DFT) methods. Intramolecular hydrogen bonds were detected in all pyranoanthocyanins, and the planarity of the compounds worsened with an increasing dielectric constant in the environment. Solvents significantly influenced the reaction enthalpies; thus, the preferred thermodynamic mechanisms of the free radical scavenging reactions were modified in different phases. This study incorporates hydrogen atom transfer (HAT), proton loss (PL), electron transfer (ET) reactions, and demethylation (De) of methoxy group mechanisms. The three pyranoanthocyanins have the capacity to capture n1+1 free radicals, where n1 represents the number of methoxy groups. In the gas phase, they prefer employing the n1-De-HAT mechanism on the guaiacyl moiety of the B ring, resulting in the formation of a stable quinone or a quinone radical to scavenge free radicals. In the benzene phase, pyranoanthocyanins trap free radicals via a PL-n1-De-HAT mechanism. In the water phase, the targeted pyranoanthocyanins may dissociate in the form of carboxylate and tend to utilize the n2-PL-n1-De-ET mechanism, where n2 and n1 represent the number of phenolic groups and methoxy groups, respectively, facilitating multiple H+/e- reactions.

Conformationally regulated “nanozyme-like” cerium oxide with multiple free radical scavenging activities for osteoimmunology modulation and vascularized osseointegration

Given post-operative aseptic loosening in orthopedic disease treatment, osteointegration occurs at the bone-implant interface as a holistic process, including immunoregulation (e.g., macrophage polarization), angiogenesis and osteogenesis in sequence. In order to achieve early rapid and satisfactory osseointegration, different nano-shaped (nanocone, nanopolyhedron and nanoflower abbr. NC, NP & NF) cerium oxide (CeO2-x) coatings, endowed with “nanozyme-like” activities for multiple free radical elimination and osteoimmunology regulation, were hydrothermally synthesized on titanium alloy (TC4). In vitro cell experiments showed that nano-CeO2-x coated TC4 not only induced polarization of RAW264.7 cells toward M2 phenotype, but also promoted angiogenesis and vascularization of endothelial cells along with differentiation and mineralization of osteogenic precursor cells. Improvements in M2-polarized macrophage, angiogenesis, and bone regeneration were further confirmed in a rat femoral condyle model. Among the above three nano-morphologies, NF exhibited the best osseoinetegration. RNA sequencing and mechanism exploration suggested that the inhibition of PI3K-AKT signaling pathway was essential for immunomodulatory capacity of NF. In conclusion, it provided promising insights into the immunomodulatory exploitation of orthopedic implants.

Banaba Restricts Brain Damage: Neuroprotective Role in Cerebral Ischemiareperfusion Injury

Background:: Glucose regulation and energy homeostasis mitigate energy crises milieu in reperfusion injury. We investigated Banaba for its outcomes on cerebral ischemia reperfusion (IR) injury using artery occlusion in rats. The pleiotropic activity of Banaba on various debilitating mechanisms inducing reperfusion injury was evaluated. Aim:: This study aimedto evaluate the pharmacological activity of Banaba (Lagerstroemia speciosa) extract on reperfusion injury and investigate the effect of Banaba on vascular permeability, oxidative stress and cellular damage in ischemia reperfusion injury in rats. Methods:: Transient ischemia and reperfusion through occlusion of the middle cerebral artery (MCAO) lead to Cerebral IR injury in Wistar rats; it was treated with oral administration of Banaba extract (100mg/kg and 200mg/kg). The injury outcomes were evaluated after 22 hours of reperfusion by determining cellular injury, its impact on musculoskeletal coordination, multiple free radical scavenging measures (SOD, GSH, LPO) and vascular permeability of the blood-brain barrier. Result:: Banaba treatment led to a marked improvement in neurological outcomes by enhanced coordination and reduced cerebral infarct in comparison to vehicle control ischemic group. Free radical scavenging activity (SOD and GSH) was significantly better, and lipid peroxidation was reduced by Banaba treatment; it also reduced the vascular permeability of the blood-brain barrier. We observed that a lower dose of Banaba (100 mg/kg) was more effective than the higher (200 mg/kg) in ischemic rats. The anti-inflammatory and anti-oxidant activity could drive the neuroprotective outcomes of Banaba in cerebral IR injury. The critical factor of the beneficial effect of Banaba in cerebral injury is the optimization of dose in this experimental setup of reperfusion injury using rats. Conclusion:: The recovery of injury could be attributed to Banaba’s multi-factorial effect targeting free radicals, inflammation, and necrosis during ischemiareperfusion injury.

One-pot synthesis of ultra-stable polyvinylpyrrolidone-modified MnO2 nanoparticles for efficient radiation protection

Radiobiological damage can be caused by radiation, and easy preparation of long-term stable radioprotectors is helpful for timely and efficient response to radiation emergencies. This study develops an ultra-stable radioprotector for rapid nuclear emergency with a simple preparing method. First of all, polyvinylpyrrolidone-modified MnO2 nanoparticles (PVP-MnO2 NPs) are obtained by one-pot synthesis with ultra-stability (remaining for at least three years) and multiple free radical scavenging activities. In the synthesis process, PVP acts as a reducing agent, a surfactant (soft template), and a steric stabilizer. PVP-MnO2 NPs can improve the survival rates of irradiated cells by effectively scavenging free radicals and protecting DNA from radiation damage. Besides, PVP-MnO2 NPs can also prevent peripheral blood cell and organ damage induced by radiation, and improve the survival rate of irradiated mice. Finally, PVP-MnO2 NPs are mainly metabolized by liver and kidney in mice, and basically excreted 72 h after administration. These results indicate that PVP-MnO2 NPs exhibit good biosafety and radioprotection activity, which is significant for the development of radioprotection agents.

Serum Free Radical Scavenging Capacity Profiles of Patients with Chronic Obstructive Pulmonary Disease.

Oxidative stress is an important mechanism for the development and progression of chronic obstructive pulmonary disease (COPD). It may also contribute to systemic manifestation in patients with COPD. Reactive oxygen species (ROS) including free radicals play a crucial role in oxidative stress in COPD. The aims of this study were to determine serum scavenging capacity profile against multiple free radicals and to evaluate its correlation with pathophysiology, exacerbations, and prognosis in patients with COPD. Serum scavenging capacity profile against multiple free radicals comprising hydroxyl radical (•OH), superoxide radical (O2 -•), alkoxy radical (RO•), methyl radical (•CH3), alkylperoxyl radical (ROO•), and singlet oxygen (1O2) was assessed using the multiple free-radical scavenging method in 37 patients with COPD (mean age, 71 years; mean forced expiratory volume in 1 s, 55.2% predicted). The severity of emphysema was evaluated by Goddard classification on chest computed tomography. Exacerbations were recorded prospectively for 1 year and the overall mortality was assessed 5 years after the initial assessment. •OH scavenging capacity was significantly decreased (p < 0.05) and O2 -• and •CH3 scavenging capacity tended to decrease in patients with COPD compared to that in healthy controls. On the other hand, ROO• scavenging capacity tended to increase. In addition, RO• scavenging capacity was associated with severity of emphysema (p < 0.05) and exacerbation frequency (p < 0.02). There was a difference in the profile of the scavenging capacity between survived and deceased patients with COPD for 5 years after initial assessment. Characteristic profile of free radical scavenging capacity can provide insight into the pathophysiology and prognosis of patients with COPD.

Multiple free radical scavenging reactions of flavonoids

The multiple free radical scavenging reactions of flavonoids have been studied considering the gas, benzene, and water phases by applying density functional theory (DFT). Intramolecular hydrogen-bonds are found in all the most stable geometries of flavonoids and can reduce the antioxidant activity of hydroxyl groups, acting as hydrogen-bond donors (5−OH, 3−OH and 3’−OH), while enhancing the antioxidant activity of hydroxyl groups, acting as hydrogen-bond acceptors (4’−OH). In the gas and benzene phases, all of the flavonoids first prefer performing continuous di-hydrogen atom transfer (HAT) reaction from the B ring OH groups to trap two free radicals with the formation of stable quinones for ampelopsin, taxifolin, dihydro orobol and eriodictyol and benzodioxole for hesperetin. They would trap the third free radical via the HAT in the gas phase. In the benzene phase, ampelopsin also favours to apply HAT to trap the third free radical, and the other flavonoids would use the sequential proton loss electron transfer (SPLET) mechanism. In the water phase, the investigated flavonoids would first perform consecutive proton loss (PL) reactions from all of the OH groups with the formation of polyanions. The multiple PL reactions begin from the 7−OH group. The second PL reaction prefers performing in the OH groups on the B benzene ring due to the better delocalization of the negative charge via conjugation over the entire skeleton. The polyanions of the investigated flavonoids scavenge three free radicals via three consecutive ET reactions.

Multiple free radical scavenging reactions of aurones

A series of naturally occurring 3′,4′-dihydroxy aurones have been studied with regard to multiple free radical scavenging reactions in the gas and two liquid phases using density functional theory (DFT). All of the aurones prefer to perform (2 + n)-HAT mechanism to trap 2 + n free radicals, where n is the sum of the numbers of catechol and guaiacyl units in the gas and benzene phases. The second HAT reaction favours occurring in the same catechol moiety of the first HAT mechanism occurring OH group due to the formation of a stable quinone and the highly exothermic step of the final stable product formation. The catechol and guaiacyl moieties show increased potency for the second and fourth H+/e‒ reactions. In the water phase, aurones can perform multiple H+/e‒ reactions through n1PL-ET-n2HAT-(n+1-n2)ET mechanism, where n1 is the number of OH groups and n2 is the number of guaiacyl moieties.

Simultaneous evaluation of antioxidative serum profiles facilitates the diagnostic screening of autism spectrum disorder in under-6-year-old children

This case–control study aimed to assess oxidative stress alterations in autism spectrum disorder (ASD). We used the MULTIS method, an electron spin resonance-based technique measuring multiple free radical scavenging activities simultaneously, in combination with conventional oxidative stress markers to investigate the ability of this MULTIS approach as a non-behavioural diagnostic tool for children with ASD. Serum samples of 39 children with ASD and 58 age-matched children with typical development were analysed. The ASD group showed decreased hydroxyl radical (·OH) and singlet oxygen scavenging activity with increased serum coenzyme Q10 oxidation rate, indicating a prooxidative tendency in ASD. By contrast, scavenging activities against superoxide (O2·−) and alkoxyl radical (RO·) were increased in the ASD group suggesting antioxidative shifts. In the subgroup analysis of 6-year-olds or younger, the combination of ·OH, O2·−, and RO· scavenging activities predicted ASD with high odds ratio (50.4), positive likelihood (12.6), and percentage of correct classification (87.0%). Our results indicate that oxidative stress in children with ASD is not simply elevated but rather shows a compensatory shift. MULTIS measurements may serve as a very powerful non-behavioural tool for the diagnosis of ASD in children.

Olive fruit debittering significantly alters its antioxidant activity as evaluated with multiple free-radical scavenging ability

Raw olive fruits taste bitter and are not edible without debittering. Common debittering process promotes the loss of olive antioxidant activity and the magnitude of loss depends on the debittering reagent used. Antioxidant activity was evaluated as the scavenging ability that was determined with multiple free-radical scavenging (MULTIS) method, where the scavenging abilities against five reactive oxygen species (HO·, O2−·, RO·, t-BuOO·, and 1O2) were determined. Significant change in the scavenging activity of debittered olive was found in four debittering methods, i.e., sodium hydroxide, sodium hydrogen carbonate, ethanol, and sodium chloride treatments. Results indicated that the scavenging activities lowered by 60–90% after most debittering processes. Sodium chloride treatment least affected the scavenging activity. Based on the MULTIS measurements for the antioxidant components and debittering reagents, the rate constants of antioxidant compounds with four ROS were determined and the antioxidant activity that depends on the method of debittering is discussed. Oleuropein, olive-related antioxidant compound, showed high scavenging abilities against HO· (k = 6.70 × 109 M−1 s−1), RO· (k = 4.69 × 106 M−1 s−1), and 1O2 (k = 1.74 × 107 M−1 s−1). This study suggests that functionality and taste do not always come together. MULTIS method is useful in comparative antioxidant capacity studies in foods.

Free radical scavenging potency of ellagic acid and its derivatives in multiple H+/e‒ processes

The reaction energetics of the multiple free radical scavenging mechanisms of ellagic acid and its derivatives were studied by DFT method. Ellagic acid and its derivatives that bear catechol or guaiacyl moieties can proceed multiple free radical scavenging processes. Intramolecular hydrogen-bonds were found in the most stable geometries of the investigated compounds and can influence the antioxidant activity of the related groups and hydrogen atom/proton loss sequence. The stronger hydrogen-bond, the weaker antioxidant activity of the hydrogen atom/proton-donating group. The preferred mechanisms vary among different phases. All of the investigated compounds prefer to trap free radicals by multiple HAT mechanisms in gas and benzene phases. The second HAT reaction preferably occurs in the same catechol or guaiacyl unit of the first HAT group with the formation of stable quinone or benzodioxole. The catechol and guaiacyl moieties not only retain high free radical scavenging ability of the parent compounds but even show increased potency for the second and fourth H+/e‒ reactions. In water phase, ellagic acid and its derivatives would proceed consecutively PL reactions from the OH groups. The formed di/tri/tetra-anion would proceed one/four electron transfers following with single/double SPLET mechanism and electron donation reactions until forming the stable quinone or benzodioxole.

Free-radical scavenging activity of radioprotectors: comparison between clinically used radioprotectors and natural antioxidants

Clinically used radioprotectors, amifostine and cysteamine, have been shown to possess free-radical scavenging activities. Natural antioxidants also possess free-radical scavenging activities, some of which have been shown to have radioprotective capability. We carried out a quantitative determination of the scavenging abilities in amifostine and cysteamine and compared the potencies with natural antioxidants by using multiple free-radical scavenging method. Overall, amifostine and cysteamine showed scavenging activity as potent as natural antioxidants. We found a correlation between scavenging activity and radioprotective efficiency that was previously determined in rat thymocytes. These correlations are indicative that natural antioxidants can be effective radioprotectors.

Ultrathin two-dimensional polydopamine nanosheets for multiple free radical scavenging and wound healing.

Novel 2D polydopamine nanosheets were successfully prepared by using a simple but effective "bottom-up" synthesis method. The ultrathin polydopamine nanosheets exhibit excellent multiple free radical scavenging activities including DPPH˙ and ABTS˙+ free radicals, especially O2˙-. Full-thickness skin defect regeneration was accelerated by treatment with the nanosheets.

Comparative Profiling of Clove Extract and Its Component Antioxidant Activities Against Five Reactive Oxygen Species Using Multiple Free Radical Scavenging

Comparative Profiling of Clove Extract and Its Component Antioxidant Activities Against Five Reactive Oxygen Species Using Multiple Free Radical Scavenging

Heat treatments of ginger root modify but not diminish its antioxidant activity as measured with multiple free radical scavenging (MULTIS) method.

Ginger (Zingiber officinale Rosc.) root (or rhizome) has been reported to have antioxidant properties such as reactive oxygen species scavenging activities. Using multiple free-radical scavenging method, we have newly determined the scavenging abilities of ginger roots against five reactive oxygen species, i.e., HO•, O2−•, RO•, tert-BuOO•, and 1O2. After heating grated ginger roots at 80°C for 2 h, nearly 50% decrease in scavenging ability was recorded against 1O2 and tert-BuOO•. Conversely, the O2−• scavenging ability increased by about 56% after heat treatment. Based on the antioxidant activity measurement of the ginger’s components, i.e., 6-gingerol, 6-shogaol, and zingerone, active species acting as antioxidant capacity of ginger was shown. Additionally, ginger’s antioxidant capacity was quantitatively compared with that of rosemary extract, indicating that rosemary is peroxyl specific scavenger while ginger has higher scavenging ability against HO• and 1O2.

21 - Reevaluation of hemodialysis effects on oxidative stress

Patients with advanced-stage chronic renal failure (CKD) are exposed to strong oxidative stress, and hemodialysis (HD) is considered to improve this. Multiple reports have been published on this topic, including our previous reports (J Am Soc Nephrol1997). However, recent advances have revealed that the oxidative stress in CKD does not simply increase unidirectionally. By using the newly developed electron spin resonance (ESR)-based analytical methods, we reevaluated the effects of HD on the oxidative status of patients with CKD. Two methods, namely multiple free radical scavenging assay (MULTIS), which evaluates scavenging activities against multiple reactive oxygen species (ROS) using CYPMPO as a spin trap, and iStrap, which is a sensitive method to detect lipid-derived carbon-center radicals using a spin trapDPhPMPO, were used in this study. Thirty-three patients undergoing maintenance HDwere enrolled. Informed consent was obtained before the trial. Thirteen cases were complicated with type 2 diabetes. Confirming our previous result, serum hydroxyl radical scavenging activity was significantly improved after HD. By contrast, scavenging activities against alkoxyl and alkylperoxyl radicals were significantly reduced after HD, which suggests a deterioration of the radical scavenging system downstream of the radical chain reaction. These reductions in scavenging activities were more obvious in patients with diabetes. The changes in the signal intensity of DPhPMPO in the whole tested group varied, whereas that of the diabetic patients was increased after HD, consistent with the alkylperoxyl radical findings. The superoxide scavenging activity was higher in the CKD subjects than that in the non-CKD subjects before HD, which then decreased after HD. These results indicate that the HD process does not simply decrease oxidative stress. Although intensive improvements have been made on the materials used in the HD session, such as the dialyzer membranes, ROS downstream of radical chain reactions are still not adequately controlled.

Monoterpene’s multiple free radical scavenging capacity as compared with the radioprotective agent cysteamine and amifostine

Monoterpenes are major active components of lavender, thyme, and mint. The X-ray radioprotective activity of pure monoterpenes is attributed to their scavenging ability against active species, but so far no firm evidence has been demonstrated. The objective of this study is to quantitatively determine antioxidant abilities of monoterpenes and collate it with radioprotective activity. Using multiple free-radical scavenging (MULTIS) method, we have determined the scavenging abilities of monoterpenes (linalool, thymol, and menthol) against six active species. A previous study has shown that the monoterpene linalool is a radioprotector for cellular systems, therefore, its scavenging ability was compared with known radioprotective agents such as cysteamine and amifostine. Results indicated that the monoterpene menthol but not linalool is a potent scavenger of reactive oxygen species and its scavenging magnitude is comparable to cysteamine and amifostine. This paper is first to show a correlation between ROS scavenging ability and radioprotective action.

Abstract WMP119: Neurovascular Unit Protection Using Nitroxide Radicals-containing Nanoparticles (TEMPO-RNP) for Cerebral Ischemia-reperfusion Injury in Mice

Purpose: Reperfusion injury after thrombolytic therapy or mechanical thrombectomy would adverse neurological outcome. Generation of reactive oxygen species (ROS) due to reperfusion is relevant for aggravation. The development of drug therapy for scavenging free radical is expected to lead to better neurological prognosis. We developed a new core-shell type nanoparticle, RNP (radical containing nanoparticle), which consists of micelle containing 4-amino-TEMPO. The purpose of this study is to evaluate an efficacy of intra-arterial injection of RNP after reperfusion using tMCAO mice model. Methods: C57BL/6J mice underwent tMCAO for 60 minutes and received RNP by intra-arterial injection from common carotid artery. We evaluated infarction size, neurological scale, and Evans blue extravasation at 24h after reperfusion. RNP distribution was detected by rhodamine labeling. We further examined immunofluorescense of CD31, Occludin, TUNEL, dihydroethydium, and 8-hydroxy-deoxyguanosine (8-OHdG). Multiple free radical scavenging capacity of ischemic hemisphere was analyzed by Electron Paramagnetic Resonance (EPR). Results: RNPs were detected in endothelial cells and around neuronal cells in the ischemic lesion. The infarction size, neurological scale, Evans blue extravasation of the mice treated by RNP were significantly lower than the mice treated by PBS , control group. Intra-arterial RNP treatment preserved endothelium and expression of occludin in the ischemic brain. Further, apoptosis of neuronal cells and production of superoxide anions and 8OHdG were suppressed. By using EPR, multiple ROS scavenging capacity (•OH, •ROO, •O 2 - ) of the ischemic brain treated by RNP were higher. Conclusions: These results suggest that intra-arterial injection of RNP have efficacy of neurovascular unit protection and reduce infarction volume by improving multiple ROS scavenging capacity.

Seasonal variations of oxygen radical scavenging ability in rosemary leaf extract

This investigation demonstrates that the oxygen radical scavenging ability of rosemary leaf extract has significant seasonal variations. The scavenging ability of rosemary leaf extract was quantitatively evaluated for five active oxygen species by using the ESR spin-trapping method. It was found that leaves that were picked in the cold season showed higher scavenging ability than those picked in the warm season. Measurement of the scavenging rate in pure rosmarinic acid and caffeic acid indicated that the scavenging ability in the warm season was mainly derived from rosmarinic acid. In the boiled extract, rosmarinic acid decomposed into caffeic acid. Therefore, a marked increase in the scavenging ability against superoxide and singlet oxygen in the boiled extract is in line with the high activity of caffeic acid. This study demonstrates that the multiple free radical scavenging method can be a useful method in comparative antioxidant capacity studies of plant extracts.