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Fetal undernutrition establishes the foundations for hypertension development, with oxidative stress being a key hallmark. A growing interest in nutraceuticals for treating hypertension and environmental waste concerns prompted the present study aiming to evaluate whether supplementation with a polyphenol enriched extract from cocoa shell (CSE), a by‐product from the chocolate industry with antioxidant properties, reduces hypertension of developmental origin, thus improving mesenteric resistance artery (MRA) vasodilatation. Adult male and female offspring from rats exposed to 50% food restriction from mid‐gestation (maternal undernutrition, MUN) and controls were used. Supplementation was given through a gelatine (vehicle, VEH) or containing CSE (250 mg kg−1 day−1) 5 days week−1 for 3 weeks. Systolic blood pressure (SBP) was assessed by tail‐cuff plethysmography. MRA function was studied by wire myography, and superoxide anion and nitric oxide were investigated by fluorescent indicators and confocal microscopy. Compared to control‐VEH, MUN‐VEH males showed significantly higher SBP, reduced MRA as well as relaxation to ACh, sodium nitroprusside and the AMPK agonist 5‐aminoimidazole‐4‐carboxamide riboside, but not to isoproterenol. In MUN males, endothelial endothelium‐derived hyperpolarizing factor and nitric oxide were unaltered, but MRA released a vasoconstrictor prostanoid and produced higher levels of superoxide anion. CSE normalized blood pressure and improved all above‐mentioned MRA alterations in MUN males without an effect on control counterparts, except the reduction of superoxide anion. MUN‐VEH females were normotensive and only showed a tendency towards larger superoxide anion production, which was abolished by CSE. CSE supplementation reduces SBP improving endothelium‐dependent and independent MRA vasodilatation, related to local superoxide anion reduction, being a potential nutraceutical ingredient to counteract hypertension, in addition to contributing to the circular economy. Key points: Fetal undernutrition induces hypertension in males associated with deficient resistance artery vasodilatation, being normalized by cocoa shell extract (CSE).Release of a cyclooxygenase‐derived contractile factor is the main endothelial alteration, which is abolished by CSE.AMPK and soluble guanylyl cyclase‐mediated relaxation are also reduced in smooth muscle cells from maternal undernutrition resistance arteries, being improved by CSE.Vascular oxidative damage caused by excess superoxide anion generation can account for impaired vasodilatation, which is improved by CSE.The capacity of CSE to improve relaxation is probably related to its antioxidant bioactive factors, and thus cocoa shell is a potential food by‐product to treat hypertension. [ABSTRACT FROM AUTHOR]

Background: Disinfection by-products used to obtain drinking water, including halomethanes (HMs) such as CH2Cl2, CHCl3, and BrCHCl2, induce cytotoxicity and hyperproliferation in human lung fibroblasts (MRC-5). Enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) modulate these damages through their biotransformation processes, potentially generating toxic metabolites. However, the role of the oxidative stress response in cellular hyperproliferation, modulated by nuclear factor-kappa B (NF-κB), remains unclear. Methods: In this study, MRC-5 cells were treated with these compounds to evaluate reactive oxygen species (ROS) production, lipid peroxidation, phospho-NF-κB/p65 (Ser536) levels, and the activities of SOD, CAT, and GPx. Additionally, the interactions between HMs and ROS with the IκBα/NF-κB/p65 complex were analyzed using molecular docking. Results: Correlation analysis among biomarkers revealed positive relationships between pro-oxidant damage and antioxidant responses, particularly in cells treated with CH2Cl2 and BrCHCl2. Conversely, negative relationships were observed between ROS levels and NF-κB/p65 levels in cells treated with CH2Cl2 and CHCl3. The estimated relative free energy of binding using thermodynamic integration with the p65 subunit of NF-κB was −3.3 kcal/mol for BrCHCl2, −3.5 kcal/mol for both CHCl3 and O2•, and −3.6 kcal/mol for H2O2. Conclusions: Chloride and bromide atoms were found in close contact with IPT domain residues, particularly in the RHD region involved in DNA binding. Ser281 is located within this domain, facilitating the phosphorylation of this protein. Similarly, both ROS interacted with the IPT domain in the RHD region, with H2O2 forming a side-chain oxygen interaction with Leu280 adjacent to the phosphorylation site of p65. However, the negative correlation between ROS and phospho-NF-κB/p65 suggests that steric hindrance by ROS on the C-terminal domain of NF-κB/p65 may play a role in the antioxidant response. [ABSTRACT FROM AUTHOR]

Superoxide dismutase (SOD) is widely present in plants and plays a crucial role in defending against oxidative stress and preventing tissue damage. This study discovered that the PagSOD2a gene in 84K poplar (Populus alba x P. glandulosa) exhibits a distinct capacity to be induced in response to salt stress. To delve into the pivotal role of PagSOD2a in conferring salt tolerance, the entire PagSOD2a fragment was successfully cloned from 84K poplar and the potential function of PagSOD2a was explored using bioinformatics and subcellular localization. PagSOD2a was found to encode a CuZn-SOD protein localized in chloroplasts. Furthermore, six CuZn-SOD family members were identified in poplar, with closely related members displaying similar gene structures, indicating evolutionary conservation. Morphological and physiological indexes of transgenic 84K poplar overexpressing PagSOD2a (OE) were compared with non-transgenic wild-type (WT) plants under salt stress. The OE lines (OE1 and OE3) showed improved growth performance, characterized by increased plant height and fresh weight, along with reduced malondialdehyde (MDA) content and electrolyte leakage rate under salt stress. Meanwhile, overexpression of PagSOD2a significantly augmented CuZn-SOD and total SOD enzyme activities, leading to a reduction in superoxide anion accumulation and an enhancement of salt tolerance. Additionally, co-expression and multilayered hierarchical gene regulatory network (ML-hGRN) mediated by PagSOD2a constructed using transcriptome data revealed that PagSOD2a gene may be directly regulated by SPL13, NGA1b and FRS5, as well as indirectly regulated by MYB102 and WRKY6, in response to salt stress. These findings provide a theoretical and material foundation for further elucidating the function of PagSOD2a under salt stress and for developing salt-tolerant poplar varieties. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) including the superoxide anion (O2•−) are typically studied in cell cultures using fluorescent dyes, which provide only discrete single-point measurements. These methods lack the capabilities for assessing O2•− kinetics and release in a quantitative manner over long monitoring times. Herein, we present the fabrication and application of an electrochemical biosensor that enables real-time continuous monitoring of O2•− release in cell cultures for extended periods (> 8 h) using an O2•− specific microelectrode. To achieve the sensitivity and selectivity requirements for cellular sensing, we developed a biohybrid system consisting of superoxide dismutase (SOD) and Ti3C2Tx MXenes, deposited on a gold microwire electrode (AuME) as O2•− specific materials with catalytic amplification through the synergistic action of the enzyme and the biomimetic MXenes-based structure. The biosensor demonstrated a sensitivity of 18.35 nA/μM with a linear range from 147 to 930 nM in a cell culture medium. To demonstrate its robustness and practicality, we applied the biosensor to monitor O2•− levels in human leukemia monocytic THP-1 cells upon stimulation with lipopolysaccharide (LPS). Using this strategy, we successfully monitored LPS-induced O2•− in THP-1 cells, as well as the quenching effect induced by the ROS scavenger N-acetyl-l-cysteine (NAC). The biosensor is generally useful for exploring the role of oxidative stress and longitudinally monitoring O2•− release in cell cultures, enabling studies of biochemical processes and associated oxidative stress mechanisms in cellular and other biological environments. [ABSTRACT FROM AUTHOR]

Ovarian tissue vitrification is associated with multiple events that promote accumulation of ROS (reactive oxygen species) which culminate in follicular apoptosis. Thus, this study was aimed at evaluating the role of melatonin in vitrification and culture of feline (Felis catus) ovarian tissue. In phase 1, domestic cat ovaries were fragmented into equal circular pieces of 1.5 mm diameter by 1 mm thickness and divided into four groups (fresh control and 3 treatments). The treatments were exposed to vitrification solutions supplemented with melatonin at 0 M, 10−9 M, and 10−7 M, then vitrified-warmed, histologically evaluated and assayed for ROS. Consequently, phase 2 experiment was designed wherein ovarian fragments were divided into two groups. One group was exposed to vitrification solution without melatonin and the other with 10−7 M melatonin supplementation, then vitrified-warmed and cultured for ten days with fresh ovarian fragments as control prior to assessment for histology, immunohistochemistry (Ki-67, MCM-7 and caspase-3) and ROS. Concentration of ROS was lower (p = 0.0009) in 10−7 M supplemented group in addition to higher proportion of grade 1 follicles. After culture, proportions of intact and activated follicles were higher (p < 0.05) in melatonin supplemented group evidenced by higher expression of Ki-67 and MCM-7. Follicular apoptosis was lower in melatonin supplemented group. In conclusion, melatonin at 10−7 M concentration preserved follicular morphological integrity while reducing ROS concentration in vitrified-warmed feline ovarian tissue. It has also promoted the follicular viability and activation with reduced apoptosis during in vitro culture of vitrified-warmed feline ovarian tissue. • Melatonin 10−7 M suppressed reactive oxygen species in vitrified cat ovarian tissue. • Primordial follicle activation was improved by melatonin supplementation at 10−7 M. • Melatonin promoted viability of vitrified-warmed and cultured feline ovarian tissue. • Melatonin exhibited antiapoptotic role in vitrified-warmed feline ovarian tissue. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is a multifunctional signalling molecule involved in the regulation of plant ontogenesis and adaptation to different adverse environmental factors, in particular to osmotic stress. Understanding NO-induced plant protection is important for the improvement of plant stress tolerance and crop productivity under global climate changes. The root system is crucial for plant survival in a changeable environment. Damages that it experiences under water deficit conditions during the initial developmental periods seriously affect the viability of the plants. This work was devoted to the comparative analysis of the pretreatment of wheat seedlings through the root system with NO donor sodium nitroprusside (SNP) for 24 h on various parameters of redox homeostasis under exposure to osmotic stress (PEG 6000, 12%) over 0.5–24 h. The active and exhausted solutions of SNP, termed as (SNP/+NO) and (SNP/−NO), respectively, were used in this work at a concentration of 2 × 10−4 M. Using biochemistry and light microscopy methods, it has been revealed that osmotic stress caused oxidative damages and the disruption of membrane cell structures in wheat roots. PEG exposure increased the production of superoxide (O2•−), hydrogen peroxide (H2O2), malondialdehyde (MDA), and the levels of electrolyte leakage (EL) and lipid peroxidation (LPO). Stress treatment enhanced the activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT), the excretion of proline, and the rate of cell death and inhibited their division. Pretreatment with (SNP/+NO) decreased PEG-induced root damages by differently regulating the antioxidant enzymes under stress conditions. Thus, (SNP/+NO) pretreatment led to SOD, APX, and CAT inhibition during the first 4 h of stress and stimulated their activity after 24 h of PEG exposure when compared to SNP-untreated or (SNP/−NO)-pretreated and stress-subjected plants. Osmotic stress triggered the intense excretion of proline by roots into the external medium. Pretreatment with (SNP/+NO) in contrast with (SNP/−NO) additionally increased stress-induced proline excretion. Our results indicate that NO is able to mitigate the destructive effects of osmotic stress on the roots of wheat seedlings. However, the mechanisms of NO protective action may be different at certain periods of stress exposure. [ABSTRACT FROM AUTHOR]

Photocatalytic oxygen reduction reactions and water oxidation reactions are extremely promising green approaches for massive H2O2 production. Nonetheless, constructing effective photocatalysts for H2O2 generation is critical and still challenging. Since the network topology has significant impacts on the electronic properties of two dimensional (2D) polymers, herein, for the first time, we regulated the H2O2 photosynthetic activity of 2D covalent organic frameworks (COFs) by topology. Through designing the linking sites of the monomers, we synthesized a pair of novel COFs with similar chemical components on the backbones but distinct topologies. Without sacrificial agents, TBD‐COF with cpt topology exhibited superior H2O2 photoproduction performance (6085 and 5448 μmol g−1 h−1 in O2 and air) than TBC‐COF with hcb topology through the O2‐O2⋅−‐H2O2, O2‐O2⋅−‐O21‐H2O2, and H2O‐H2O2 three paths. Further experimental and theoretical investigations confirmed that during the H2O2 photosynthetic process, the charge carrier separation efficiency, O2⋅− generation and conversion, and the energy barrier of the rate determination steps in the three channels, related to the formation of *OOH, *O21, and *OH, can be well tuned by the topology of COFs. The current study enlightens the fabrication of high‐performance photocatalysts for H2O2 production by topological structure modulation. [ABSTRACT FROM AUTHOR]

Total antioxidant capacity (TAC) can be evaluated by detecting the content of antioxidants, such as ascorbic acid, based on the enzyme-mimetic activity of nanomaterials. Herein, we fabricated a 3D-V2O5/NC nanocomposite using a self-templating strategy, which achieved ultrafine particles (∼2.5 nm), a porous carbon layer, large specific surface area (152.4 m2/g), N-doping and heterogeneous structure. The strong catalytic activity of 3D-V2O5/NC resulted from the integrated effect between the ultrafine structure of V2O5 nanoparticles and the 3D porous nitrogen-doped carbon framework, effectively increasing the number of active sites. This nanozyme presented a higher catalytic activity than its components or precursors in the nanocomposite (e.g., VN/NC, NC, V2O5, and VO2/g-C3N4). ROS scavenging experiments confirmed that the dual enzyme-like activity of 3D-V2O5/NC (catalase-like and oxidase-like) resulted from their co-participation of ‧O2-, h+ and ‧OH, among which ‧O2- played a crucial role in the catalytic color reaction. By virtue of the 3D-V2O5/NC nanoenzyme activity and TMB as a chromogenic substrate, the mixed system of 3D-V2O5/NC + TMB + H2O2 provided a low detection limit (0.03 μM) and suitable recovery (93.0-109.5%) for AA. Additionally, a smartphone-based colorimetric application was developed employing "Thing Identify" software to evaluate TAC in beverages. The colorimetric sensor and smartphone-detection platform provide a better or comparable analytical performance for TAC assessment in comparison to commercial ABTS test kits. The newly developed smartphone-based colorimetric platform presents several prominent advantageous, such as low cost, simple/rapid operation, and feasibility for outdoor use.

Chondrocytes are mechanosensitive cells able to sense and respond to external mechanical stimuli through the process of mechanotransduction. Previous studies have demonstrated that mechanical stimulation causes mitochondrial deformation leading to mitochondrial reactive oxygen species (ROS) release in a dose‐dependent manner. For this reason, we focused on elucidating the role of mitochondrial ROS as anabolic signaling molecules in chondrocyte mechanotransduction. Chondrocyte‐seeded agarose gels were subjected to mechanical stimuli and the effect on matrix synthesis, ROS production, and mitogen‐activated protein kinases (MAPK) signaling was evaluated. Through the use of ROS‐specific staining, superoxide anion was the primary ROS released in response to mechanical stimuli. The anabolic effect of mechanical stimulation was abolished in the presence of electron transport chain inhibitors (complexes I, III, and V) and superoxide anion scavengers. Subsequent studies were centered on the involvement of MAPK pathways (ERK1/2, p38, and JNK) in the mechanotransduction cascade. While disruption of the ERK1/2 pathway had no apparent effect, the anabolic effect of mechanical stimulation was abolished in the presence of p38 and JNK pathway inhibitors. This suggest the involvement of apoptosis stimulating kinase 1 (ASK1), an upstream redox‐sensitive MAP3K shared by both the JNK and p38 pathways. Future experiments will focus on the involvement of the thioredoxin‐ASK1 complex which disassociates in the presence of oxidative stress, allowing ASK1 to phosphorylate several MAP2Ks. Overall, these findings indicate superoxide anion as the primary ROS released in response to mechanical stimuli and that the resulting anabolic effect on chondrogenic matrix biosynthesis arises from the ROS‐dependent activation of the p38 and JNK MAPKs. [ABSTRACT FROM AUTHOR]

Peumus boldus , a tree native to Chile, is extensively used for medicinal purposes due to its richness in alkaloids and antioxidant polyphenols. A species of galling insect, Dasineura sp. induces structural and chemical changes on P. boldus stems while its galls are established and developed. Taking into account the antioxidant properties of P. boldus polyphenols, it would be expected that Dasineura sp. induces changes in the accumulation sites, chemical profile, and antioxidant activity of the P. boldus stem polyphenols, related to different reactive oxygen species (ROS) production levels during gall development. Dasineura sp. induces changes in the accumulation sites of total polyphenols, flavonols, and lignin, redirecting their accumulation toward the sites of greatest production of H2O2 and O2.−. Although changes in total polyphenol content would be expected, this did not vary significantly between non-galled and galled stems. However, the galling insect induced changes in the profile and concentration of soluble polyphenols, leading to the gall extracts' antioxidant capacity decreasing significantly during the maturation and senescence stages. Additionally, during the maturation stage, lignin deposition increases in the more peripheral gall tissues, which also contributes to ROS dissipation. The differences in the different gall developmental stages' antioxidant activity could be related to the identity and concentration of phenolic compounds in each gall extract, rather than to the total phenol content. Regardless of the mechanisms involved, the dissipation of the ROS generated by Dasineura sp. activity occurs, restoring the redox balance in galls and guaranteeing the success of the inducer. [ABSTRACT FROM AUTHOR]

Flashes of superoxide anion (O2−) in mitochondria are generated spontaneously or during the opening of the permeability transition pore (mPTP) and a sudden change in the metabolic state of a cell. Under certain conditions, O2− can leave the mitochondrial matrix and perform signaling functions beyond mitochondria. In this work, we studied the kinetics of the release of O2− and H2O2 from isolated mitochondria upon mPTP opening and the modulation of the metabolic state of mitochondria by the substrates of respiration and oxidative phosphorylation. It was found that mPTP opening leads to suppression of H2O2 emission and activation of the O2− burst. When the induction of mPTP was blocked by its antagonists (cyclosporine A, ruthenium red, EGTA), the level of substrates of respiration and oxidative phosphorylation and the selective inhibitors of complexes I and V determined the type of reactive oxygen species (ROS) emitted by mitochondria. It was concluded that upon complete and partial reduction and complete oxidation of redox centers of the respiratory chain, mitochondria emit H2O2, O2−, and nothing, respectively. The results indicate that the mPTP- and substrate-dependent switching of the type of ROS leaving mitochondria may be the basis for O2−- and H2O2-selective redox signaling in a cell.

Background: Disinfection by-products used to obtain drinking water, including halomethanes (HMs) such as CH2Cl2, CHCl3, and BrCHCl2, induce cytotoxicity and hyperproliferation in human lung fibroblasts (MRC-5). Enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) modulate these damages through their biotransformation processes, potentially generating toxic metabolites. However, the role of the oxidative stress response in cellular hyperproliferation, modulated by nuclear factor-kappa B (NF-κB), remains unclear. Methods: In this study, MRC-5 cells were treated with these compounds to evaluate reactive oxygen species (ROS) production, lipid peroxidation, phospho-NF-κB/p65 (Ser536) levels, and the activities of SOD, CAT, and GPx. Additionally, the interactions between HMs and ROS with the IκBα/NF-κB/p65 complex were analyzed using molecular docking. Results: Correlation analysis among biomarkers revealed positive relationships between pro-oxidant damage and antioxidant responses, particularly in cells treated with CH2Cl2 and BrCHCl2. Conversely, negative relationships were observed between ROS levels and NF-κB/p65 levels in cells treated with CH2Cl2 and CHCl3. The estimated relative free energy of binding using thermodynamic integration with the p65 subunit of NF-κB was −3.3 kcal/mol for BrCHCl2, −3.5 kcal/mol for both CHCl3 and O2•, and −3.6 kcal/mol for H2O2. Conclusions: Chloride and bromide atoms were found in close contact with IPT domain residues, particularly in the RHD region involved in DNA binding. Ser281 is located within this domain, facilitating the phosphorylation of this protein. Similarly, both ROS interacted with the IPT domain in the RHD region, with H2O2 forming a side-chain oxygen interaction with Leu280 adjacent to the phosphorylation site of p65. However, the negative correlation between ROS and phospho-NF-κB/p65 suggests that steric hindrance by ROS on the C-terminal domain of NF-κB/p65 may play a role in the antioxidant response.

Irrigation with water containing a variety of microcystins (MCs) may pose a potential threat to the normal growth of agricultural plants. To investigate the phytotoxicity of MC-LR at environmental concentrations on rice (Oryza sativa L.), the characteristics of uptake and accumulation in plant tissues, as well as a series of key physio-biochemical process changes in leaves of rice seedlings, were measured at concentrations of 0.10, 1.0, 10.0, and 50.0 μg·L−1 in hydroponic nutrient solutions for 7, 15, 20, and 34 days. Results showed that MC-LR could be detected in rice leaves and roots in exposure groups; however, a significant accumulation trend of MC-LR in plants (BCF > 1) was only found in the 0.10 μg·L−1 group. The time-course study revealed a biphasic response of O2•− levels in rice leaves to the exposure of MC-LR, which could be attributed to the combined effects of the antioxidant system and detoxification reaction in rice. Exposure to 1.0–50.0 μg·L−1 MC-LR resulted in significant depletion of GSH and MDA contents in rice leaves at later exposure times (15–34 days). Low MC-LR concentrations promoted nitric oxide synthase (NOS) activity, whereas high concentrations inhibited NOS activity during the later exposure times. The reduced sucrose synthase (SS) activities in rice exposed to MC-LR for 34 days indicated a decrease in the carbon accumulation ability of plants, and therefore may be directly related to the inhibition of plant growth under MC exposure. These findings indicate that the normal physiological status would be disrupted in terrestrial plants, even under exposure to low concentrations of MC-LR. [ABSTRACT FROM AUTHOR]

There is a growing interest in the use of natural compounds to tackle inflammatory diseases and cancers. However, most of them face the bioavailability and solubility challenges to reaching cellular compartments and exert their potential biological effects. Polyphenols belong to that class of molecules, and numerous efforts have been made to improve and overcome these problems. Curcumin is widely studied for its antioxidant and anti-inflammatory properties as well as its use as an anticancer agent. However, its poor solubility and bioavailability are often a source of concern with disappointing or unexpected results in cellular models or in vivo, which limits the clinical use of curcumin as such. Beside nanoparticles and liposomes, cyclodextrins are one of the best candidates to improve the solubility of these molecules. We have used lysine and cyclodextrin to form a water-soluble curcumin complex, named NDS27, in which potential anti-inflammatory effects were demonstrated in cellular and in vivo models. Herein, we investigated for the first time its direct free radicals scavenging activity on DPPH/ABTS assays as well as on hydroxyl, superoxide anion, and peroxyl radical species. The ability of NDS27 to quench singlet oxygen, produced by rose bengal photosensitization, was studied, as was the inhibiting effect on the enzyme-catalyzed oxidation of the co-substrate, luminol analog (L012), using horseradish peroxidase (HRP)/hydrogen peroxide (H2O2) system. Finally, docking was performed to study the behavior of NDS27 in the active site of the peroxidase enzyme. [ABSTRACT FROM AUTHOR]

Oxidative stress is a state when the content of free radicals in a living organism is excessive. Molecules of free radical nature start a chain reaction that disrupts the integrity of cells, leading to their damage or death. The article examines the issue of intensification of oxidative stress processes and changes in the antioxidant defense system during the occurrence, development, and treatment of diseases of various etiologies. The principles of antioxidant/prooxidant balance regulation at the physiological and biochemical levels in living organisms are discussed. It was determined that the phenomenon of oxidative stress, as a completely special type of stress, is mediated by free radicals that have a destructive effect on the membranes of living cells. Free radical molecules are damaging agents for nucleic acids, proteins and lipids. The leading role in biological systems is played by oxygen free radicals, namely superoxide anion. The system of antioxidant protection, which prevents the harmful effects of oxidative stress on living organisms, is described in detail. The work describes the components of the antioxidant protection system, such as electron acceptors – vitamins E and K3; acceptors of superoxide radical anions – methionine, cysteine; scavengers of hydroxyl radicals – aliphatic alcohols; factors for detoxification of toxic products of lipid peroxidation, tocopherol, ionol, superoxide dismutase, glutathione peroxidase system, chelators of metals with variable valence (complexons) and others. According to the nature and mechanism of action, antioxidant protection agents are divided into hydrophilic and hydrophobic, enzymatic (catalase, superoxide dismutase, glutathione peroxidase system, glutathione, ascorbic acid, adrenaline, serotonin, tocopherols, retinoids, flavonoids, phospholipids, ceruloplasmin) and non-enzymatic factors. It is noted that in the human body, oxidative stress is the cause or an important component of many serious diseases, such as oncological pathologies, neurodegenerative processes (atherosclerosis and Alzheimer’s disease), diseases of the gastrointestinal tract, as well as aging. Although in some cases, oxidative stress can act as a protective mechanism in the body. Thus, the human immune system uses oxidative stress to fight pathogens, and some reactive oxygen species can serve as mediators in signal transmission during the immune response. Therefore, the biochemical mechanism of the development of many diseases of different etiology is closely related to disturbances in the antioxidant defense system and the occurrence of oxidative stress.

Background. Histamine is one of the versatile biogenic amines with multiple roles in the immune response and allergic disorders. Histamine and ATP can act as ligands in the body. In plasma, ATP is a potent vasodilator that stimulates the formation of NO and prostaglandins and, very importantly, can offset local sympathetic vasoconstriction. Adenosine triphosphate is released into plasma from erythrocytes and endothelial cells, and the plasma concentration increases in both the feed artery and the vein draining the contracting skeletal muscle. Taking this into account, it is important to study the effect of histamine in combination with quercetin, which inhibits the release of histamine from cellular depots, on the content of the superoxide anion and ATP in the blood plasma. Materials and Methods. Nonlinear white male rats were used for the experimental studies. Quercetin solutions were added to whole blood to a final concentration of 0.1; 0.3; 0.5; 1; 3; 5 mM. In other experiments, histamine solution was added to the blood to final concentration of 0.01; 0.1; 1; 10 μM. In a series of experiments, histamine (0.01 and 10 μM) and quercetin (0.1; 0.5; 3; 5 mM) were added to the blood in various possible combinations. Blood plasma was used in each experimental group. The blood to which saline was added was used as control. The content of superoxide anion and adenosine triphosphate was measured in the selected samples. Results and Discussion. Histamine, quercetin, as well as their combined action lead to the intensification of superoxide anion generation in the blood plasma of rats. Quercetin is known to be an antioxidant, but some of our studies have shown the opposite effect. Quercetin causes an increase in the ATP content in the blood plasma of rats. Histamine causes the same effect only at concentrations of 0.1 and 10 µM. Likewise, the combined administration of histamine and quercetin into the blood increased the ATP content. The results of ANOVA test prove that both histamine and quercetin have the same effect on the release of superoxide anion and ATP from blood cells into plasma. Their combined action only strengthens the effect of releasing the studied products. Conclusion. Quercetin, histamine and their combined action cause an increase in the generation of superoxide anion and ATP in the blood plasma of rats.

Significance: Redox signaling through mitochondrial reactive oxygen species (mtROS) has a key role in several mechanisms of regulated cell death (RCD), necroptosis, ferroptosis, pyroptosis, and apoptosis, thereby decisively contributing to inflammatory disorders. The role of mtROS in apoptosis has been extensively addressed, but their involvement in necrotic-like RCD has just started being elucidated, providing novel insights into the pathophysiology of acute inflammation. Recent Advances: p53 together with mtROS drive necroptosis in acute inflammation through downregulation of sulfiredoxin and peroxiredoxin 3. Mitochondrial hydroorotate dehydrogenase is a key redox system in the regulation of ferroptosis. In addition, a noncanonical pathway, which generates mtROS through the Ragulator-Rag complex and acts via mTORC1 to promote gasdermin D oligomerization, triggers pyroptosis. Critical Issues: mtROS trigger positive feedback loops leading to lytic RCD in conjunction with the necrosome, the inflammasome, glutathione depletion, and glutathione peroxidase 4 deficiency. Future Directions: The precise mechanism of membrane rupture in ferroptosis and the contribution of mtROS to ferroptosis in inflammatory disorders are still unclear, which will need further research. Mitochondrial antioxidants may provide promising therapeutic approaches toward acute inflammatory disorders. However, establishing doses and windows of action will be required to optimize their therapeutic potential, and to avoid potential adverse side effects linked to the blockade of beneficial mtROS adaptive signaling. Antioxid. Redox Signal. 39, 708–727. [ABSTRACT FROM AUTHOR]

Oxidative stress is a state when the content of free radicals in a living organism is excessive. Molecules of free radical nature start a chain reaction that disrupts the integrity of cells, leading to their damage or death. The article examines the issue of intensification of oxidative stress processes and changes in the antioxidant defense system during the occurrence, development, and treatment of diseases of various etiologies. The principles of antioxidant/prooxidant balance regulation at the physiological and biochemical levels in living organisms are discussed. It was determined that the phenomenon of oxidative stress, as a completely special type of stress, is mediated by free radicals that have a destructive effect on the membranes of living cells. Free radical molecules are damaging agents for nucleic acids, proteins and lipids. The leading role in biological systems is played by oxygen free radicals, namely superoxide anion. The system of antioxidant protection, which prevents the harmful effects of oxidative stress on living organisms, is described in detail. The work describes the components of the antioxidant protection system, such as electron acceptors – vitamins E and K3; acceptors of superoxide radical anions – methionine, cysteine; scavengers of hydroxyl radicals – aliphatic alcohols; factors for detoxification of toxic products of lipid peroxidation, tocopherol, ionol, superoxide dismutase, glutathione peroxidase system, chelators of metals with variable valence (complexons) and others. According to the nature and mechanism of action, antioxidant protection agents are divided into hydrophilic and hydrophobic, enzymatic (catalase, superoxide dismutase, glutathione peroxidase system, glutathione, ascorbic acid, adrenaline, serotonin, tocopherols, retinoids, flavonoids, phospholipids, ceruloplasmin) and non-enzymatic factors. It is noted that in the human body, oxidative stress is the cause or an important component of many serious diseases, such as oncological pathologies, neurodegenerative processes (atherosclerosis and Alzheimer’s disease), diseases of the gastrointestinal tract, as well as aging. Although in some cases, oxidative stress can act as a protective mechanism in the body. Thus, the human immune system uses oxidative stress to fight pathogens, and some reactive oxygen species can serve as mediators in signal transmission during the immune response. Therefore, the biochemical mechanism of the development of many diseases of different etiology is closely related to disturbances in the antioxidant defense system and the occurrence of oxidative stress. [ABSTRACT FROM AUTHOR]

Currently, there is no consensus on estimating the malignant potential of Carotid Body Tumor (CBT) and the only way to predict a metastatic CBT is through DOTANOC Positron Emission Tomography (PET) scan. There is a well-established correlation between CBT and superoxide anions inside tumor cells. The purpose of this pilot study was to measure superoxide anions inside CBT cells and find if these can be used as marker to predict malignant potential of CBT. The results were also co-related with findings of DOTANOC PET scan retrospectively. The CBT tissue from 10 patients was stained using a fluorogenic dye and superoxide anions were measured by analysis of fluorescent image. The patients were divided into two groups – First group with four patients having potentially malignant CBT based upon clinico-surgical characteristics and second group with the rest of the six patients. It was seen that the superoxide anions were highest in the first group which included patients with metastatic carotid body tumor, patients with multiple paragangliomas and patient with positive family history (p = 0.011). The same patients also had metastasis and multiple tumors detected on DOTANOC PET scan. It was concluded that measuring superoxide anions in excised tumor tissue can be used to estimate malignant potential of CBT and can identify patients who truly require DOTANOC PET scan; without affecting the treatment, as it is an expensive investigation involving ionizing radiation and may not be available in all centres. [ABSTRACT FROM AUTHOR]

In this work, 3-nitrophenylferrocene (3-NPF) and bis-3- nitrophenylferrocene (bis-3-NPF) were synthesized through the arylation of ferrocene by diazotasing of 3-nitroaniline by sodium nitrite in the presence of H2SO4 to form meta-nitrobenzendiazonium sulfide. The synthesized compounds were characterized by IR infrared and NMR magnetic resonance spectroscopy (1H, 13C and DEPT). The superoxide scavenging effect was assessed by electrochemical assay; cyclic voltammetry, the DPPH scavenging assay and total antioxidant capacity were assessed using spectrophotometric assay. In this paper, the antioxidant capacity index (IC50) towards supreroxide anion radical, DPPH radical and TAC were determined, we found that the IC50 of compounds against superoxide ranged from 1.212 to 2.709mg/ml, the lowest value of IC50 was detected in bis-3-NPF, the DPPH radical inhibition capacities are in the order of ascorbic acida-Tocopherolbis-3-NPF3- NPF with IC50 respectively of 0.0063mg/ml, 0.0134mg/ml, 0.773mg/ml and 1. 44mg/ml and the maximum Mo(VI) reducing activity was observed at high concentrations (0.8 mg/ml), the TAC of the compounds was found to be in the following order: Bis-3-NPF 3-NPF. The antioxidant activity coefficients (Ka), the interaction coefficients (Kb) and the binding free energy of these two ferrocene derivatives towards the superoxide radical were determined using the values of the intensities of the anodic currents from the cyclic voltammograms of the O2/O2 - couple. [ABSTRACT FROM AUTHOR]

Abstract Ferroptosis is an iron-dependent regulated cell death that suppresses tumor growth. It is activated by extensive peroxidation of membrane phospholipids caused by oxidative stress. GPX4, an antioxidant enzyme, reduces these peroxidized membrane phospholipids thereby inhibiting ferroptosis. This enzyme has two distinct subcellular localization; the cytosol and mitochondria. Dihydroorotate dehydrogenase (DHODH) complements mitochondrial GPX4 in reducing peroxidized membrane phospholipids. It is the rate-limiting enzyme in de novo pyrimidine nucleotide biosynthesis. Its role in ferroptosis inhibition suggests that DHODH inhibitors could have two complementary mechanisms of action against tumors; inhibiting de novo pyrimidine nucleotide biosynthesis and enhancing ferroptosis. However, the link between mitochondrial function and ferroptosis, and the involvement of DHODH in the ETC suggests that its role in ferroptosis could be modulated by the Warburg effect. Therefore, we reviewed relevant literature to get an insight into the possible effect of this metabolic reprogramming on the role of DHODH in ferroptosis. Furthermore, an emerging link between DHODH and cellular GSH pool has also been highlighted. These insights could contribute to the rational design of ferroptosis-based anticancer drugs. Video Abstract

Abstract Background Expression systems for lactic acid bacteria have been developed for metabolic engineering applications as well as for food-grade recombinant protein production. But the industrial applications of lactic acid bacteria as cell factories have been limited due to low biomass formation resulted in low efficiency of biomanufacturing process. Limosilactobacillus reuteri KUB-AC5 is a safe probiotic lactic acid bacterium that has been proven as a gut health enhancer, which could be developed as a mucosal delivery vehicle for vaccines or therapeutic proteins, or as expression host for cell factory applications. Similar to many lactic acid bacteria, its oxygen sensitivity is a key factor that limits cell growth and causes low biomass production. The aim of this study is to overcome the oxidative stress in L. reuteri KUB-AC5. Several genes involved in oxidative and anti-oxidative stress were investigated, and strain improvement for higher cell densities despite oxidative stress was performed using genetic engineering. Results An in-silico study showed that L. reuteri KUB-AC5 genome possesses an incomplete respiratory chain lacking four menaquinone biosynthesis genes as well as a complete biosynthesis pathway for the production of the precursor. The presence of an oxygen consuming enzyme, NADH oxidase (Nox), leads to high ROS formation in aerobic cultivation, resulting in strong growth reduction to approximately 25% compared to anaerobic cultivation. Recombinant strains expressing the ROS scavenging enzymes Mn-catalase and Mn-superoxide dismutase were successfully constructed using the pSIP expression system. The Mn-catalase and Mn-SOD-expressing strains produced activities of 873 U/ml and 1213 U/ml and could minimize the ROS formation in the cell, resulting in fourfold and sevenfold higher biomass formation, respectively. Conclusions Expression of Mn-catalase and Mn-SOD in L. reuteri KUB-AC5 successfully reduced oxidative stress and enhanced growth. This finding could be applied for other lactic acid bacteria that are subject to oxidative stress and will be beneficial for applications of lactic acid bacteria for cell factory applications.

Several rare genetic variations of human XDH have been shown to alter xanthine oxidoreductase (XOR) activity leading to impaired purine catabolism. However, XOR is a multi-functional enzyme that depending upon the environmental conditions also expresses oxidase activity leading to both O2·- and H2O2 and nitrite (NO2−) reductase activity leading to nitric oxide (·NO). Since these products express important, and often diametrically opposite, biological activity, consideration of the impact of XOR mutations in the context of each aspect of the biochemical activity of the enzyme is needed to determine the potential full impact of these variants. Herein, we show that known naturally occurring hXDH mutations do not have a uniform impact upon the biochemical activity of the enzyme in terms of uric acid (UA), reactive oxygen species (ROS) and nitric oxide ·NO formation. We show that the His1221Arg mutant, in the presence of xanthine, increases UA, O2·- and NO generation compared to the WT, whilst the Ile703Val increases UA and ·NO formation, but not O2·-. We speculate that this change in the balance of activity of the enzyme is likely to endow those carrying these mutations with a harmful or protective influence over health that may explain the current equipoise underlying the perceived importance of XDH mutations. We also show that, in presence of inorganic NO2−, XOR-driven O2·- production is substantially reduced. We suggest that targeting enzyme activity to enhance the NO2−-reductase profile in those carrying such mutations may provide novel therapeutic options, particularly in cardiovascular disease.

Endoplasmic reticulum, the largest cellular organelle where protein synthesis, folding, transportation, and the maintenance of Ca2+ homeostasis occurred, is sensitive to the imbalance of its inner environment. Particularly, overproduction of reactive oxygen species in endoplasmic reticulum region can initiate endoplasmic reticulum stress and is tightly related to many metabolic diseases. In this respect, to retain normal function of endoplasmic reticulum, it is highly important to synthesize antioxidants with endoplasmic reticulum-targeting capability for precisely clearing excessively generated reactive oxygen species in endoplasmic reticulum. Herein, we demonstrate the preparation of endoplasmic reticulum-targeting Se-doped carbon nanodots and assays with HeLa cells as well as in vivo tests with mice have shown that the prepared carbon nanodots can significantly eliminate both •OH and O2•−. Experimental results declared that the fabricated carbon nanodots with powerful scavenging capabilities toward •OH and O2•-, low cytotoxicity and endoplasmic reticulum targetability can be utilized to protect cells against raised levels of reactive oxygen species in endoplasmic reticulum. What’s more, the fabricated carbon nanodots effectively alleviated phorbol 12-myristate 13-acetate induced ear inflammation in live mice.

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Precisely reporting the inflammatory microenvironment, which can provide important basis for disease diagnosis and progression determination, is always challenging. In this work, we develop a targeting peptide-conjugated chemiluminescent reporter (OFF), which can be recognized by in-situ circulated neutrophils once injected, and then transported to the inflamed tissues characterized with overexpressed superoxide anion (O 2 −), assisted by the chemotaxis natural of neutrophils. Subsequently, the chemiluminescent probe can particularly respond to O 2 − to release the caged photons (ON) for visualizing inflammatory diseases such as subcutaneous tumor, colorectal cancer peritoneal metastasis (CCPM), ear swelling and kidney failure. The chemiluminescent probe provides a reliable tool to early detect inflammation and precisely excise micrometastatic lesions under optical guidance. This study provides a potential approach for improving the performance of luminophore in advanced bioimaging applications. [Display omitted] • An "off-to-on" chemiluminescent probe based on the structure of Schaap's dioxetanes is developed in this work • The probe transportation can inherit neutrophils' inherent inflammation-chemotaxis characteristic. • The probe can selectively respond to superoxide anion rich in inflammatory tissues. • The probe can specially and precisely image the foci of inflammatory disease. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS), including superoxide anion, are involved in regulating various signaling pathways and are also responsible for oxidative stress. Sensing superoxide anion is of particular importance due to its biological significance. One potential approach is to use Coelenterazine as a chemiluminescent probe for the dynamic sensing of this ROS. In this study, we investigated the superoxide anion-triggered chemiluminescence of native Coelenterazine and two halogenated analogs and found that they showed a ~100-fold enhancement of light emission in aqueous solution, which was significantly reduced in methanol and nonexistent in aprotic solvents. In fact, Coelenterazine showed more intense light emission in aprotic solvents and, interestingly, although the light emission of the analogs seemed relatively unaffected by the solvents, their chemiluminescence was significantly quenched in water compared to methanol and, especially, to aprotic media. This suggests that the quenching effect observed for Coelenterazine is responsible for the differences in aqueous media, rather than an intrinsic enhanced emission by the analogs. In summary, we present Coelenterazine analogs that could serve as a basis for enhanced sensing of superoxide anion, providing information that could further our understanding of this chemiluminescent system. [ABSTRACT FROM AUTHOR]

Ferroptosis is an iron-dependent regulated cell death that suppresses tumor growth. It is activated by extensive peroxidation of membrane phospholipids caused by oxidative stress. GPX4, an antioxidant enzyme, reduces these peroxidized membrane phospholipids thereby inhibiting ferroptosis. This enzyme has two distinct subcellular localization; the cytosol and mitochondria. Dihydroorotate dehydrogenase (DHODH) complements mitochondrial GPX4 in reducing peroxidized membrane phospholipids. It is the rate-limiting enzyme in de novo pyrimidine nucleotide biosynthesis. Its role in ferroptosis inhibition suggests that DHODH inhibitors could have two complementary mechanisms of action against tumors; inhibiting de novo pyrimidine nucleotide biosynthesis and enhancing ferroptosis. However, the link between mitochondrial function and ferroptosis, and the involvement of DHODH in the ETC suggests that its role in ferroptosis could be modulated by the Warburg effect. Therefore, we reviewed relevant literature to get an insight into the possible effect of this metabolic reprogramming on the role of DHODH in ferroptosis. Furthermore, an emerging link between DHODH and cellular GSH pool has also been highlighted. These insights could contribute to the rational design of ferroptosis-based anticancer drugs. 8YjiDgdRtHZ2Rfs-RM3Nkf Video Abstract [ABSTRACT FROM AUTHOR]

For the first time, lux biosensors of E. coli and the nematode Caenorhabditis elegans were used to study the genotoxicity of beta-propiolactone (BPL) used in the production of inactivated viral vaccines as an inactivator. It has been shown that the DNA-damaging activity of BPL is due not only to its ability to bind to bacterial DNA, but also to the ability to generate in the cell reactive oxygen species such as superoxide anions and peroxide, which have genotoxic activity. It was found that BPL in a dose-dependent manner, starting from a concentration of 0.001 mol/L, reduces the survival of bacteria. However, the intensity of expression of the antioxidant defense gene of superoxide dismutase soxS and the DNA repair gene colD increased. BPL-induced DNA breaks in nematode cells were detected by electrophoresis. The antioxidant acetylcysteine reduced the genotoxic effects of BPL on both bacteria and the nematode. [ABSTRACT FROM AUTHOR]

Background: Expression systems for lactic acid bacteria have been developed for metabolic engineering applications as well as for food-grade recombinant protein production. But the industrial applications of lactic acid bacteria as cell factories have been limited due to low biomass formation resulted in low efficiency of biomanufacturing process. Limosilactobacillus reuteri KUB-AC5 is a safe probiotic lactic acid bacterium that has been proven as a gut health enhancer, which could be developed as a mucosal delivery vehicle for vaccines or therapeutic proteins, or as expression host for cell factory applications. Similar to many lactic acid bacteria, its oxygen sensitivity is a key factor that limits cell growth and causes low biomass production. The aim of this study is to overcome the oxidative stress in L. reuteri KUB-AC5. Several genes involved in oxidative and anti-oxidative stress were investigated, and strain improvement for higher cell densities despite oxidative stress was performed using genetic engineering. Results: An in-silico study showed that L. reuteri KUB-AC5 genome possesses an incomplete respiratory chain lacking four menaquinone biosynthesis genes as well as a complete biosynthesis pathway for the production of the precursor. The presence of an oxygen consuming enzyme, NADH oxidase (Nox), leads to high ROS formation in aerobic cultivation, resulting in strong growth reduction to approximately 25% compared to anaerobic cultivation. Recombinant strains expressing the ROS scavenging enzymes Mn-catalase and Mn-superoxide dismutase were successfully constructed using the pSIP expression system. The Mn-catalase and Mn-SOD-expressing strains produced activities of 873 U/ml and 1213 U/ml and could minimize the ROS formation in the cell, resulting in fourfold and sevenfold higher biomass formation, respectively. Conclusions: Expression of Mn-catalase and Mn-SOD in L. reuteri KUB-AC5 successfully reduced oxidative stress and enhanced growth. This finding could be applied for other lactic acid bacteria that are subject to oxidative stress and will be beneficial for applications of lactic acid bacteria for cell factory applications. [ABSTRACT FROM AUTHOR]

Superoxide anion (O2•−) is an important reactive oxygen species (ROS), and plays critical roles in biological systems. ER stress has close relation with many metabolic diseases, and could lead to the abnormal production of ROS including O2•−. Herein, we present an ER-targeting probe (ER-Tf) for the detection of O2•− in living cells. The probe ER-Tf used triflate as the response site for O2•−, and employed p-methylbenzenesulfonamide as ER-targeting moiety. In response to O2•−, the triflate of the probe ER-Tf converted to hydroxyl group, providing strong blue emission under the excitation of ultraviolet light. The probe ER-Tf exhibited high sensitivity and selectivity to O2•−. Bioimaging experiments showed that the probe ER-Tf can be applied to detect O2•− at ER, and also demonstrated that rotenone could increase the generation of O2•− in living cells, while the O2•− level at ER showed no remarkable change during ferroptosis. [ABSTRACT FROM AUTHOR]

Copper-zinc superoxide dismutase (SOD1) is an antioxidant enzyme that catalyzes the disproportionation of superoxide anion to hydrogen peroxide and molecular oxygen (dioxygen). The yeast Saccharomyces cerevisiae lacking SOD1 (Δsod1) is hypersensitive to the superoxide anion and displays a number of oxidative stress-related alterations in its phenotype. We compared proteomes of the wild-type strain and the Δsod1 mutant employing two-dimensional gel electrophoresis and detected eighteen spots representing differentially expressed proteins, of which fourteen were downregulated and four upregulated. Mass spectrometry-based identification enabled the division of these proteins into functional classes related to carbon metabolism, amino acid and protein biosynthesis, nucleotide biosynthesis, and metabolism, as well as antioxidant processes. Detailed analysis of the proteomic data made it possible to account for several important morphological, biochemical, and physiological changes earlier observed for the SOD1 mutation. An example may be the proposed additional explanation for methionine auxotrophy. It is concluded that protein comparative profiling of the Δsod1 yeast may serve as an efficient tool in the elucidation of the mutation-based systemic alterations in the resultant S. cerevisiae phenotype. [ABSTRACT FROM AUTHOR]

Irrigation with water containing a variety of microcystins (MCs) may pose a potential threat to the normal growth of agricultural plants. To investigate the phytotoxicity of MC-LR at environmental concentrations on rice (Oryza sativa L.), the characteristics of uptake and accumulation in plant tissues, as well as a series of key physio-biochemical process changes in leaves of rice seedlings, were measured at concentrations of 0.10, 1.0, 10.0, and 50.0 μg·L−1 in hydroponic nutrient solutions for 7, 15, 20, and 34 days. Results showed that MC-LR could be detected in rice leaves and roots in exposure groups; however, a significant accumulation trend of MC-LR in plants (BCF > 1) was only found in the 0.10 μg·L−1 group. The time-course study revealed a biphasic response of O2•− levels in rice leaves to the exposure of MC-LR, which could be attributed to the combined effects of the antioxidant system and detoxification reaction in rice. Exposure to 1.0–50.0 μg·L−1 MC-LR resulted in significant depletion of GSH and MDA contents in rice leaves at later exposure times (15–34 days). Low MC-LR concentrations promoted nitric oxide synthase (NOS) activity, whereas high concentrations inhibited NOS activity during the later exposure times. The reduced sucrose synthase (SS) activities in rice exposed to MC-LR for 34 days indicated a decrease in the carbon accumulation ability of plants, and therefore may be directly related to the inhibition of plant growth under MC exposure. These findings indicate that the normal physiological status would be disrupted in terrestrial plants, even under exposure to low concentrations of MC-LR.

There is a growing interest in the use of natural compounds to tackle inflammatory diseases and cancers. However, most of them face the bioavailability and solubility challenges to reaching cellular compartments and exert their potential biological effects. Polyphenols belong to that class of molecules, and numerous efforts have been made to improve and overcome these problems. Curcumin is widely studied for its antioxidant and anti-inflammatory properties as well as its use as an anticancer agent. However, its poor solubility and bioavailability are often a source of concern with disappointing or unexpected results in cellular models or in vivo, which limits the clinical use of curcumin as such. Beside nanoparticles and liposomes, cyclodextrins are one of the best candidates to improve the solubility of these molecules. We have used lysine and cyclodextrin to form a water-soluble curcumin complex, named NDS27, in which potential anti-inflammatory effects were demonstrated in cellular and in vivo models. Herein, we investigated for the first time its direct free radicals scavenging activity on DPPH/ABTS assays as well as on hydroxyl, superoxide anion, and peroxyl radical species. The ability of NDS27 to quench singlet oxygen, produced by rose bengal photosensitization, was studied, as was the inhibiting effect on the enzyme-catalyzed oxidation of the co-substrate, luminol analog (L012), using horseradish peroxidase (HRP)/hydrogen peroxide (H2O2) system. Finally, docking was performed to study the behavior of NDS27 in the active site of the peroxidase enzyme.

Background: Early Life Stress (ELS) may exert long-lasting biological effects, e.g., on PBMC energy metabolism and mitochondrial respiration. Data on its effect on brain tissue mitochondrial respiration is scarce, and it is unclear whether blood cell mitochondrial activity mirrors that of brain tissue. This study investigated blood immune cell and brain tissue mitochondrial respiratory activity in a porcine ELS model.Methods: This prospective randomized, controlled, animal investigation comprised 12 German Large White swine of either sex, which were weaned at PND (postnatal day) 28–35 (control) or PND21 (ELS). At 20–24 weeks, animals were anesthetized, mechanically ventilated and surgically instrumented. We determined serum hormone, cytokine, and “brain injury marker” levels, superoxide anion (O2•¯) formation and mitochondrial respiration in isolated immune cells and immediate post mortem frontal cortex brain tissue.Results: ELS animals presented with higher glucose levels, lower mean arterial pressure. Most determined serum factors did not differ. In male controls, TNFα and IL-10 levels were both higher than in female controls as well as, no matter the gender in ELS animals. MAP-2, GFAP, and NSE were also higher in male controls than in the other three groups. Neither PBMC routine respiration and brain tissue oxidative phosphorylation nor maximal electron transfer capacity in the uncoupled state (ETC) showed any difference between ELS and controls. There was no significant relation between brain tissue and PBMC, ETC, or brain tissue, ETC, and PBMC bioenergetic health index. Whole blood O2•¯ concentrations and PBMC O2•¯ production were comparable between groups. However, granulocyte O2•¯ production after stimulation with E. coli was lower in the ELS group, and this effect was sex-specific: increased O2•¯ production increased upon stimulation in all control animals, which was abolished in the female ELS swine.Conclusion: This study provides evidence that ELS i) may, gender-specifically, affect the immune response to general anesthesia as well as O2•¯ radical production at sexual maturity, ii) has limited effects on brain and peripheral blood immune cell mitochondrial respiratory activity, and iii) mitochondrial respiratory activity of peripheral blood immune cells and brain tissue do not correlate.

Classically, superoxide anion O2•− and reactive oxygen species ROS play a dual role. At the physiological balance level, they are a by-product of O2 reduction, necessary for cell signalling, and at the pathological level they are considered harmful, as they can induce disease and apoptosis, necrosis, ferroptosis, pyroptosis and autophagic cell death. This revision focuses on understanding the main characteristics of the superoxide O2•−, its generation pathways, the biomolecules it oxidizes and how it may contribute to their modification and toxicity. The role of superoxide dismutase, the enzyme responsible for the removal of most of the superoxide produced in living organisms, is studied. At the same time, the toxicity induced by superoxide and derived radicals is beneficial in the oxidative death of microbial pathogens, which are subsequently engulfed by specialized immune cells, such as neutrophils or macrophages, during the activation of innate immunity. Ultimately, this review describes in some depth the chemistry related to O2•− and how it is harnessed by the innate immune system to produce lysis of microbial agents. [ABSTRACT FROM AUTHOR]

In the last years, research proofs have confirmed that hydrogen sulfide (H2S) plays an important role in various physio-pathological processes, such as oxidation, inflammation, neurophysiology, and cardiovascular protection; in particular, the protective effects of H2S in cardiovascular diseases were demonstrated. The interest in H2S-donating molecules as tools for biological and pharmacological studies has grown, together with the understanding of H2S importance. Here we performed a comparative study of a series of H2S donor molecules with different chemical scaffolds and H2S release mechanisms. The compounds were tested in human serum for their stability and ability to generate H2S. Their vasorelaxant properties were studied on rat aorta strips, and the capacity of the selected compounds to protect NO-dependent endothelium reactivity in an acute oxidative stress model was tested. H2S donors showed different H2S-releasing kinetic and produced amounts and vasodilating profiles; in particular, compound 6 was able to attenuate the dysfunction of relaxation induced by pyrogallol exposure, showing endothelial protective effects. These results may represent a useful basis for the rational development of promising H2S-releasing agents also conjugated with other pharmacophores. [ABSTRACT FROM AUTHOR]

Copyright of Brazilian Journal of Biology is the property of Instituto Internacional de Ecologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Electrochemiluminescence (ECL) of luminol is a well-established methodology in analytical chemistry and bioimaging. Developing novel strategies to enhance the ECL signal of this model emitter is a challenging but rewarding task. In this work, we introduced the high-intensity focused ultrasound (HIFU), as a pretreatment means and a non-invasive way to trigger and boost the ECL signal with a 40-fold significant enhancement in the luminol-O2 system without the addition of exogenous co-reactants. The superoxide anion (O2−•) generated in situ by HIFU was the key initiator for boosting the ECL emission as demonstrated in this study for the first time. This promising co-reactant-free strategy could find potential applications for ultrasensitive ECL detection in the analysis of complex biological entities. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tea polyphenols have been reported to have the effect of lowering uric acid. However, there are few studies on the inhibitory effects and molecular mechanisms of specific catechins on the urate‐metabolizing enzyme xanthine oxidase (XO). In this research, multiple spectroscopic methods and computer simulations were used to determine the inhibitory ability and mechanisms of epigallocatechin gallate (EGCG) and gallocatechin gallate (GCG) on XO. RESULTS: Herein, EGCG and GCG reversibly inhibited XO activity in a mixed manner, with IC50 values of 40.50 ± 0.32 and 33.60 ± 0.53 μmol L−1, and also decreased the superoxide anion radical (O2−) of the catalytic system by reducing the XO molecule and inhibiting the formation of uric acid. The combination of EGCG or GCG with allopurinol showed synergistic inhibition on XO. The binding of EGCG or GCG to XO with moderate affinity formed a stable complex by hydrogen bonds and van der Waals forces. The presence of EGCG and GCG made the structure of XO more stable and compact. The two inhibitors bound to the vicinity of flavin adenine dinucleotide (FAD) in XO, hindering the entry of substrate; thus the activity of XO was suppressed. CONCLUSION: Both EGCG and GCG are excellent natural XO inhibitors, and inhibited the activity of XO by occupying the channel of the substrate to enter the active center and interfering with the dual substrate reaction catalyzed by XO. These findings provide a scientific basis for the application of catechins in dietary supplements and medicines with lowering uric acid effects. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The photosynthetic apparatus is a major reactive oxygen species (ROS) proliferator, especially in high-light environments. The role of ROS in photoinhibition and photoacclimation mechanisms has been extensively explored, primarily in model plant species. However, little work has been performed on the topic in non-Archaeplastida organisms, such as the model heterokont species Nannochloropsis oceanica. To investigate the photoacclimation and damaging impact of singlet oxygen and superoxide anions on the photosynthetic apparatus of N. oceanica, we subjected cells to two doses of methyl viologen and rose bengal. Significant findings: Rose bengal (a singlet-oxygen photosensitizer) induced changes to the photosynthetic apparatus and PSII photochemistry mirroring high-light-acclimated cells, suggesting that singlet-oxygen signaling plays a role in the high-light acclimation of PSII. We further suggest that this singlet-oxygen pathway is mediated outside the plastid, given that rose bengal caused no detectable damage to the photosynthetic apparatus. Methyl viologen (a superoxide-anion sensitizer) induced an enhanced non-photochemical quenching response, similar to what occurs in high-light-acclimated cells. We propose that superoxide anions produced inside the plastid help regulate the high-light acclimation of photoprotective pathways. [ABSTRACT FROM AUTHOR]

The carnivorous pitcher plant, Nepenthes × ventrata (Hort. ex Fleming = N. ventricosa Blanco × N. alata Blanco), produces passive traps containing digestive fluid. Although reactive oxygen species (ROS) in the fluid were detected in some pitcher plants, the participation of reactive nitrogen species (RNS) in the digestion process has not yet been examined. The aim of this work was to investigate the production of superoxide anion (O2•−), nitric oxide (NO) and peroxynitrite (ONOO−) levels in the digestive fluid of traps throughout organ development. We revealed the ROS and RNS occurrence in the digestive fluid, linked to the ROS-scavenging capacity and total phenolics content. In digestive fluid from the fed traps, NO emission was higher than in the fluid from the developed unfed pitcher. The concentration of nitrite (NO2−) decreased in the fluid from the fed traps in comparison to the unfed ones, pointing at NO2− as the key source of NO. The enhanced emission of NO was associated with lowered content of ONOO− in the fluid, probably due to lower production of O2•−. At the same time, despite a decline in total phenolics, the maximum ROS scavenging capacity was detected. In addition, ROS and RNS were noted even in closed traps, suggesting their involvement not only in digestion per se but also their action as signaling agents in trap ontogeny. [ABSTRACT FROM AUTHOR]

Background. One of the important indicators of the nutritional value of amaranth is the high content of protein and lipids in seeds. Hence, obtaining and identifying such forms of amaranth through breeding, so that they also possessed resistance to abiotic stressors, is an important task.Materials and methods. Leaves and seeds of Amaranthus cruentus L. and mutants of the second inbred generation obtained by treatment with sodium azide were analyzed. The Bradford assay was used to measure the content of total soluble protein, lipid analysis was performed by thin-layer chromatography, the state of the antioxidant system was assessed according to catalase and peroxidase activities and the rate of superoxide anion formation. Mathematical data were processed using the Statistica 10.0 software.Results. The highest concentration of total protein in seeds was 13.78 mg/g in one of the mutants obtained after treatment with 3 mM sodium azide. Fifteen fatty acids were found in amaranth seeds, and in four mutants a significant increase in the percentage of omega-6 unsaturated linoleic acid was recorded. An increase in salt tolerance compared to the control was observed in mutants No. 2 and No. 3. Mutant No. 2 under salinization demonstrated higher peroxidase activity and mutant No. 3 higher catalase activity; both mutants showed a reduced rate of superoxide anion formation compared to the control.Conclusion. Amaranth mutants identified for higher stress resistance, protein content and linoleic acid content can be recommended for further breeding to produce new cultivars of amaranth with economically valuable traits.