Pro-oxidant Activity Research Articles

Advantageous/Unfavorable Effect of Quercetin on the Membranes of SK-N-SH Neuroblastoma Cells.

Quercetin is a polyphenolic compound, the effects of which raise scientists’ doubts. The results of many experiments show that it has anticancer, antiinflammatory, and antioxidant properties, while other studies indicate its pro-oxidative and cytotoxic action. This compound can react with reactive oxygen species, and due to its chemical properties, it can be found in the hydrophobic-hydrophilic area of cells. These features of quercetin indicate that its action in cells will be associated with the modification of membranes and its participation in maintaining the redox balance. Therefore, this study distinguishes these two mechanisms and determines whether they are important for cell function. We check: (1) Whether the selected concentrations of quercetin are cytotoxic and destructive for SK-N-SH cell membranes (MTT, LDH, MDA tests) in situations with and without the applied oxidative stress; (2) what is the level of changes in the structural/mechanical properties of the lipid part of the membranes of these cells due to the presence of polyphenol molecules; and (3) whether the antioxidative action of quercetin protects the membrane against its modification. Our results show that changes in the stiffness/elasticity of the lipid part of the membrane constitute the decisive mechanism of action of quercetin, potentially influencing cellular processes whose initial stages are associated with membranes (e.g., reception of signals from the environment, transport).

The effect of acrylamide on sperm oxidative stress, total antioxidant levels, tyrosine phosphorylation, and carboxymethyl-lysine expression: A laboratory study.

BackgroundAcrylamide (AA) is a reactive molecule produced during food processing at temperatures above 120∘C.ObjectiveTo evaluate the impact of different concentrations of AA on human sperm parameters, oxidative stress and total antioxidant capacity (TAC).Materials and Methods In this laboratory study, semen samples were obtained from healthy donors referred to the Taleghani Hospital, Tehran, Iran between June and July 2019. Samples were divided into four groups (n = 10/each): one control and three treatment groups (0.5, 1, and 2 mM of AA). After 2 hr of exposure to AA, the superoxide dismutase and malondialdehyde levels were measured based on colorimetric methods. The TAC was determined by the ferric-reducing antioxidant power assay. Flow cytometry was performed to measure the intracellular reactive oxygen species generation. Also, immunohistochemistry was done to determine the effect of AA on tyrosine phosphorylation and carboxymethyl-lysine expression.ResultsResults of the study demonstrated that the motility and viability of spermatozoa were significantly decreased after AA exposure (p 0.001). This decrease was also seen in the TAC and superoxide dismutase activity as well as in the phosphotyrosine percentage compared with the control (p 0.01). However, the carboxymethyl-lysine and prooxidant activity including reactive oxygen species generation and lipid peroxidation level increased (p 0.001).Conclusion Overall, the results confirmed the detrimental effect of AA on human spermatozoa which may be due to oxidative stress and decreased total antioxidant levels. AA may reduce fertility by reducing sperm capacitation and motility.

Efficacy of Leu-Ile-Lys tripeptide in the correction of experimental urate nephrolithiasis

Aim. To study the effect of the Leu-Ile-Lys (leucine-isoleucine-lysine) tripeptide on the course of experimental urate nephrolithiasis.
 Methods. The experiment was carried out on 23 male Wistar rats weighing 200220 grams that were divided into a control (n=8, modeling of urate nephrolithiasis) and an experimental (n=15, modeling of urate nephrolithiasis + administration of Leu-Ile-Lys tripeptide) groups. The tripeptide was administered intragastrically through a tube at a dose of 11.5 mg/kg. Daily urine was collected on a weekly basis, and the activity of lactate dehydrogenase and gamma-glutamyl transpeptidase was determined. After three weeks of the experiment, the animals were euthanized, and kidneys were removed to determine the parameters of free radical oxidation [concentration of thiobarbituric acid reactive substances (TARS), total pro-oxidant and total antioxidant activity, the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX)] and conduct a morphological study in which the number and area of calculi and the condition of the renal tissues were determined. Statistical data processing was performed using the Statistica 12.0 software. We used the MannWhitney U test, the Wilcoxon signed rank test. The results are presented as median with the 25th and 75th percentiles. The differences were considered significant at p 0.05.
 Results. In the kidneys of the rats of the experimental group, the number of deposits decreased twofold, as compared with the control group (1.60.2 and 3.20.4, respectively, p=0.001). Lactate dehydrogenase activity in the urine of rats increased from 0.10 (0.06; 0.21) units/mg of creatinine per day initially to 0.75 (0.44; 1.07) units/mg creatinine per day on day 21 (p=0.012) in the control group, and from 0.10 (0.06; 0.12) units/mg creatinine per day to 0.45 (0.34; 0.71) units/mg creatinine per day on 21st day (p=0.003) in the experimental group. The concentration of thiobarbituric acid reactive substances in the experimental group was 1.2 times lower than that of the control group: 4.2 (3.9; 4.6) mol and 5.1 (4.7; 5.5) mol, respectively (p 0.001). In addition, in the kidneys of the rats of the experimental group, the total antioxidant activity was 1.3 times higher than in control: 70.4 (65.4; 74.1)% and 53.8 (33.3; 62.2)% respectively (p 0.001). Superoxide dismutase activity in the experimental group was 1.5 times higher than in the control group: 12.4 (11.0; 13.2)% against 8.1 (6.4; 13.1)% (p=0.016). Catalase activity in the experimental group was 1.2 times higher than in the control group: 31.1 (26.4; 36.1)% against 25.1 (20.3; 27.1)% (p=0.005).
 Conclusion. The Leu-Ile-Lys tripeptide has a litholytic effect, manifested in a statistically significant decrease in the activity of oxidative stress markers (p 0,001) and a twofold decrease in the average amount of uric acid kidney stones (p 0,001).

Redox Active Cerium Oxide Nanoparticles: Current Status and Burning Issues.

Research on cerium oxide nanoparticles (nanoceria) has captivated the scientific community due to their unique physical and chemical properties, such as redox activity and oxygen buffering capacity, which made them available for many technical applications, including biomedical applications. The redox mimetic antioxidant properties of nanoceria have been effective in the treatment of many diseases caused by reactive oxygen species (ROS) and reactive nitrogen species. The mechanism of ROS scavenging activity of nanoceria is still elusive, and its redox activity is controversial due to mixed reports in the literature showing pro-oxidant and antioxidant activity. In light of its current research interest, it is critical to understand the behavior of nanoceria in the biological environment and provide answers to some of the critical and open issues. This review critically analyzes the status of research on the application of nanoceria to treat diseases caused by ROS. It reviews the proposed mechanism of action and shows the effect of surface coatings on its redox activity. It also discusses some of the crucial issues in deciphering the mechanism and redox activity of nanoceria and suggests areas of future research.

Inhibition of Rac1 GTPase Decreases Vascular Oxidative Stress, Improves Endothelial Function, and Attenuates Atherosclerosis Development in Mice.

Aims: Oxidative stress and inflammation contribute to atherogenesis. Rac1 GTPase regulates pro-oxidant NADPH oxidase activity, reactive oxygen species (ROS) formation, actin cytoskeleton organization and monocyte adhesion. We investigated the vascular effects of pharmacological inhibition of Rac1 GTPase in mice.Methods and Results: We treated wild-type and apolipoprotein E-deficient (ApoE−/−) mice with Clostridium sordellii lethal toxin (LT), a Rac1 inhibitor, and assessed vascular oxidative stress, expression and activity of involved proteins, endothelial function, macrophage infiltration, and atherosclerosis development. LT-treated wild-type mice displayed decreased vascular NADPH oxidase activity and ROS production. Therapeutic LT doses had no impact on behavior, food intake, body weight, heart rate, blood pressure, vascular and myocardial function, differential blood count, and vascular permeability. ApoE−/− mice were fed a cholesterol-rich diet and were treated with LT or vehicle. LT treatment led to decreased aortic Rac1 GTPase activity, NADPH oxidase activity and ROS production, but had no impact on expression and membrane translocation of NADPH oxidase subunits and RhoA GTPase activity. LT-treated mice showed improved aortic endothelium-dependent vasodilation, attenuated atherosclerotic lesion formation and reduced macrophage infiltration of atherosclerotic plaques. Concomitant treatment of cholesterol-fed ApoE−/− mice with LT, the specific synthetic Rac1 inhibitor NSC 23766 or simvastatin comparably reduced aortic Rac1 activity, NADPH oxidase activity, oxidative stress, endothelial dysfunction, atherosclerosis development, and macrophage infiltration.Conclusions: These findings identify an important role of the small GTPase Rac1 in atherogenesis and provide a potential target for anti-atherosclerotic therapy.

P–060 Dose- dependent mitigation of lead acetate toxicity in males on embryo development in female mice

Abstract Study question Does quercetin (75 or 100 mg/kg BW/day) co-administration with lead acetate to male mice affects embryonic development in female mice? Summary answer The low-dose quercetin (75 mg/kg BW/day) ameliorated the adverse effects of lead acetate on mouse embryogenesis. What is known already Lead causes male infertility by impacting on endocrine system and spermatogenesis, and may exert undesirable effects on the offspring. The currently approved treatment for lead poisoning is the use of chelating agents, which form an insoluble complex with lead and shield it from biological targets; thus, reducing its toxicity. One of the main mechanisms of lead-induced toxicity is oxidative stress, and it has been reported that natural antioxidants can reduce the heavy metals toxicity. The aim of the present study was to examine the protective effects of quercetin on the toxicity induced by lead acetate on the embryogenesis in mice. Study design, size, duration Sexually mature (eight-week-old) NMRI male mice (n = 24) were randomly divided into four groups (n = 6 per group) receiving (i) distilled water (control group); (ii) lead acetate (150 mg/kg BW/day) dissolved in deionized water (LA); (iii) lead acetate (150 mg/kg BW/day) + quercetin (75 mg/kg BW/day) (LQ75); (IV) lead acetate (150 mg/kg BW/day) + quercetin (100 mg/kg BW/day) (LQ100). Treatments were applied daily as oral gavages for one cycle of the seminiferous epithelium (35 days). Participants/materials, setting, methods At the end of treatment administration, the males were joined with super-ovulated females, and the retrieved zygotes were cultured for evaluation of the embryo development (at 2-cell, 4-cell, 8-cell, and blastocyst stages), and blastocyst cell number using differential staining (propidium iodide and bisbenzimide). After incubation of capacitated sperm with oocytes, an ultraviolet light microscope was used following 3 min incubation with 25 µg⁄mL bisbenzamide solution for fertilization assessment. Main results and the role of chance Lead acetate (LA) treatment of male mice decreased the 2-cell stage compared with the control group (P > 0.05). There was no difference between control and LQ75, and between LA and LQ100. The other stages of embryonic development were not significantly affected by the treatment. Overall, early embryonic development in the control and LQ75 mice were better than LQ100 and LA mice. The number of cells in the trophectoderm and inner-cell mass were not affected by treatments. However, the total blastocyst cell number in the control was higher than in the other groups; there was no significant difference between LQ100, LQ75 and LA groups. Fertilization rate was not affected by the treatments (P < 0.05). Quercetin acts as a potent antioxidant at low doses, but at high doses exerts a pro-oxidant action. According to previous reports, higher concentrations of quercetin increased apoptosis and necrosis while decreasing the activities of the antioxidant enzymes. Also, it has been suggested that quercetin might disrupt the endocrine system and interfere with Sertoli cell function and sperm motility. Limitations, reasons for caution A limitation of this study is narrow dose selection; more studies are needed to determine the effective dose of quercetin in ameliorating the lead toxicity. There are also side effects of lead-quercetin chelates such as metal redistribution, essential metal loss, accumulation and persistency in intracellular sites, and peroxidation. Wider implications of the findings: Lead administration adversely impacted on the embryogenesis; on the other hand, paternal quercetin co-administration somewhat ameliorated the adverse effects of lead on mice embryogenesis. Trial registration number Not applicable

Combining Genome-Wide Gene Expression Analysis (RNA-seq) and a Gene Editing Platform (CRISPR-Cas9) to Uncover the Selectively Pro-oxidant Activity of Aurone Compounds Against Candida albicans.

Candida albicans is the major fungal cause of healthcare-associated bloodstream infections worldwide with a 40% mortality rate. The scarcity of antifungal treatments due to the eukaryotic origin of fungal cells has challenged the development of selectively antifungal drugs. In an attempt to identify novel antifungal agents, aurones SH1009 and SH9051, as synthetically bioactive compounds, have been recently documented as anti-Candida agents. Since the molecular mechanisms behind the inhibitory activities of these aurones in C. albicans are unclear, this study aimed to determine the comprehensive cellular processes affected by these aurones and their molecular targets. Genome-wide transcriptional analysis of SH1009- and SH9051-treated C. albicans revealed uniquely repressed expression in different metabolic pathways, particularly trehalose and sulfur amino acid metabolic processes for SH1009 and SH9051, respectively. In contrast, the most commonly enriched process for both aurones was the up-regulation of RNA processing and ribosomal cleavages as an indicator of high oxidative stress, suggesting that a common aspect in the chemical structure of both aurones led to pro-oxidative properties. Additionally, uniquely induced responses (iron ion homeostasis for SH1009 and arginine biosynthesis for SH9051) garnered attention on key roles for the aurone functional groups. Deletion of the transcription factor for the trehalose biosynthesis pathway, Tye7p, resulted in an SH1009-resistant mutant, which also exhibited low trehalose content, validating the primary molecular target of SH1009. Aurone SH9051 uniquely simulated an exogenous supply of methionine or cysteine, leading to sulfur amino acid catabolism as evidenced by quantifying an overproduction of sulfite. Phenyl aurone, the common structure of aurones, contributed proportionally in the pro-oxidative activity through ferric ion reduction effects leading to high ROS levels. Our results determined selective and novel molecular mechanisms for aurone SH1009 and also elucidated the diverse cellular effects of different aurones based on functional groups.

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In diabetes, one of the most important causes of morbidity and mortality is vasculopathy. Though flaxseed (FXS) is known for improving cardiovascular health, only limited studies are available on FXS concerning diabetic vascular reactivity. Hence, in this study, we studied vascular reactivity changes after FXS treatment on streptozotocin (STZ)-induced diabetic rat aortae. Female Wistar rats were divided into following four groups: control (C), FXS treated (CT), diabetic (D), and FXS treated diabetic (DT) groups. FXS (0,714 g/kg/day; orally) was started after one week of STZ injection and was given for 12 weeks, phenylephrine (Phe)-induced contractions were obtained on isolated aortic rings in the presence of indomethacin, L-NAME and superoxide dismutase (SOD), individually. Phe-responses were increased significantly in D group and completely improved after FXS intake, whereas FXS increased vascular reactivity to Phe in C group. Indomethacin incubation significantly attenuated Phe-induced contractions in all groups of aorta, particularly in D group. L-NAME incubation significantly increased Phe responses in all groups except D group. SOD incubation decreased the contractions efficiently in D group. The decreament was much lower in DT compared to D group, but reverse effects were observed in CT group. Our findings suggest FXS may provide beneficial effects on diabetes-induced vascular reactivity changes through NO and prostaglandin dependent pathways, but in healty condition FXS may have adverse effect probably via pro-oxidant activity.

Прооксидантно-антиоксидантний баланс у серці щурів з різною поведінковою активністю за умов світлової експозиції

The purpose of the article. The article shows that the effect of round-the-clock lighting causes changes in the processes of lipid peroxidation and antioxidant activity in rats, and depends on their behavioural activity. The effects of lighting on the processes of oxidative metabolism of varying degrees in the heart of resistant and unstable to emotional stress rats. Materials and methods. Investigations were carried out on 32 mature Wistar rats, divided into four groups: group 1 – animals resistant to emotional stress (intact); group 2 – intact animals unstable to emotional stress; group 3 – experimental animals resistant to emotional stress (30-day light exposure (1000 lux)); group 4 – experimental animals, unstable to emotional stress (30-day light exposure (1000 lux)). When assessing the effect of light on the state of the organism, the most important integral indicator is the behavior of animals. Therefore, during the experiment we used the observation of behavioral reactions in the test “open field”. Based on the characteristics of the behavior of animals in the “open field” rats were divided into groups resistant and unstable to emotional stress. To assess lipid peroxidation in the heart homogenate, the concentration of TBA-active products, the concentration of diene, oxidiene and triene conjugates were determined. Antioxidant processes were assessed by the increase in the concentration of TBA- active products during 1.5-hour incubation in an iron-ascorbate buffer solution, as well as by the activity of superoxide dismutase and catalase. Results and discussion. Prooxidant activity was characterized by an increase in the concentration of TBA-reactive substances in animals resistant to emotional stress. The concentration of TBA-reactive substances after 1.5-hour incubation increased in both experimental groups. Changes in the antioxidant status were illustrated by an increase in superoxide dismutase activity in the group of stress-unstable rats, whereas catalase activity increased in both experimental groups. In addition, in the group of animals resistant to emotional stress, a significant decrease in the resources of α-tocopherol and β-carotene was revealed. Conclusion. The long-term light exposure promotes the formation of end products of peroxidation in the heart of rats resistant to emotional stress and causes a decrease in antioxidant potential, regardless of behavioural activity. Antioxidant activity in the heart of emotionally stress-resistant rats is realized through both the enzyme and non-enzyme links of the antioxidant defence, while the main role in the heart of emotionally stress-resistant rats is played by superoxide dismutase activity

7-Ketocholesterol: Effects on viral infections and hypothetical contribution in COVID-19

7-Ketocholesterol, which is one of the earliest cholesterol oxidization products identified, is essentially formed by the auto-oxidation of cholesterol. In the body, 7-ketocholesterol is both provided by food and produced endogenously. This pro-oxidant and pro-inflammatory molecule, which can activate apoptosis and autophagy at high concentrations, is an abundant component of oxidized Low Density Lipoproteins. 7-Ketocholesterol appears to significantly contribute to the development of age-related diseases (cardiovascular diseases, age-related macular degeneration, and Alzheimer's disease), chronic inflammatory bowel diseases and to certain cancers. Recent studies have also shown that 7-ketocholesterol has anti-viral activities, including on SARS-CoV-2, which are, however, lower than those of oxysterols resulting from the oxidation of cholesterol on the side chain. Furthermore, 7-ketocholesterol is increased in the serum of moderately and severely affected COVID-19 patients. In the case of COVID-19, it can be assumed that the antiviral activity of 7-ketocholesterol could be counterbalanced by its toxic effects, including pro-oxidant, pro-inflammatory and pro-coagulant activities that might promote the induction of cell death in alveolar cells. It is therefore suggested that this oxysterol might be involved in the pathophysiology of COVID-19 by contributing to the acute respiratory distress syndrome and promoting a deleterious, even fatal outcome. Thus, 7-ketocholesterol could possibly constitute a lipid biomarker of COVID-19 outcome and counteracting its toxic effects with adjuvant therapies might have beneficial effects in COVID-19 patients.

Ethanolic Extracts from Agro-Industrial Co-Products Enhance Oxidative Stability of Candelilla Wax or Celluloses Derivatives Oleogels

Abstract Ethanol oleoresins obtained from orange peel, pea pod, or pomegranate peel were employed to enrich soybean oil before elaborating two types of oleogels, one made with candelilla wax, another made with a mixture of celluloses derivatives, in order to determine their effect on oleogel oxidative stability. Orange peel oleoresin obtained a higher amount of polyphenols as catechol acid equivalent (9.09 meq/g), as compared to pea pod oleoresin or pomegranate peel (8.80 and 8.55, respectively), although pomegranate peel presented the higher TEAC (1.67, twice than the other samples). Oleogels elaborated with celluloses were presented better oxidative stability (oxidative rancidity and peroxide index) as compared to samples elaborated with candelilla wax, since waxes minor constituents employed as oleogelators could promote prooxidant activity. Samples with pomegranate oleoresin presented enhanced oxidative stability. Candelilla wax has a more marked effect on the oleogels thermal properties of due to their influence on fatty acids crystallization, because in celluloses oleogels the mechanism of gelation does not imply the formation of a highly ordered secondary structure. This finding opens the possibility to, on one hand, use oleoresins to enhance the oxidative stability of oleogels; and on the other hand, to select the oleogelator, waxes, or celluloses, based on thermal properties and other aspects, depending on the further application of oleogel thinking in oleogel thermoreversible capacity.

Using a combination of chitosan, methyl jasmonate, and cyclodextrin as an effective elicitation strategy for prenylated stilbene compound production in Arachis hypogaea L. hairy root culture and their impact on genomic DNA

Peanut (Arachis hypogaea L.) hairy roots are a potential tool for stilbene compound production. This study focuses on the most efficient elicitation strategy for inducing stilbene compound production, especially for the prenylated forms of trans-arachidin-1 and trans-arachidin-3. To the best of our knowledge, this is the first report of simultaneous treatment involving chitosan (CHT), methyl jasmonate (MeJA), and cyclodextrin (CD); CHT + MeJA + CD in peanut hairy roots to induce substantial amounts of trans-arachidin-1 and trans-arachidin-3 at 72 h of the elicitation period. The results demonstrate the highest amounts of trans-arachidin-1 and trans-arachidin-3, with 684.30 ± 183.85 and 543.94 ± 171.17 mg/g dry weight of hairy roots, respectively. The highest antioxidant capacity determined by ABTS and FRAP assays was 188.95 ± 0.43 µmol Trolox/g dry weight of hairy roots and 24.61 ± 0.50 mg ascorbic acid/g dry weight of hairy roots, respectively, while the highest phenolic content was also detected in this crude extract, with 8.67 ± 0.11 mg gallic acid/g dry weight of hairy roots. The antioxidant and pro-oxidant activity of the CHT + MeJA + CD crude extract in the protection and damage of DNA is of great interest and can have major positive impacts on health promotion and disease prevention. Chitosan, methyl jasmonate, and cyclodextrin induce high stilbene compounds. The antioxidant in crude extract could scavenge free radicals and protect DNA, while pro-oxidant activity causes severe damage to genomic DNA.

Incorporation of avocado peel extract to reduce cooking-induced hazards in beef and soy burgers: A clean label ingredient

In this study, the benefits of using avocado peel extract (APE), rich in phenolic compounds, to reduce the oxidation and formation of harmful compounds resulting from cooking, were investigated. Beef and soy-based burgers with the addition of APE (0.5% and 1%) were studied after pan frying concerning proximate and physicochemical characteristics, inhibition of protein and lipid oxidation products (thiobarbituric acid reactive substances [TBARS], hexanal, and carbonyls), heterocyclic aromatic amines (HAs) and acrylamide formation. Sensory analysis was additionally performed. APE-affected proximate composition, protein, fat, and ash contents (%) were found to be markedly higher in APE-incorporated burgers (~28.32 ± 0.29, ~14.00 ± 0.01, and ~1.57 ± 0.05, respectively), compared with the controls (~26.55 ± 0.51, ~12.77 ± 0.32, and ~1.48 ± 0.16, respectively). Lower concentrations of TBARS, hexanal, and carbonyls were observed in APE-treated burgers on Days 1 and 10, post-cooking, compared to controls. Overall, it was found that APE had a greater protective effect than the positive control (sodium ascorbate incorporated) in beef burgers. In soy burgers, the positive control demonstrated pro-oxidant activity. The addition of 0.5% APE was found to inhibit HAs and acrylamide formation in beef and soy burgers. Although the addition of APE affected the color of both meat and soy burgers, it did not impact consumer preference. It was therefore concluded that APE extract might be a suitable clean-label alternative to synthetic antioxidants, and that it can protect and increase the nutritional value of meat and meat-free burgers.

Maclurin exerts anti-cancer effects in human osteosarcoma cells via prooxidative activity and modulations of PARP, p38, and ERK signaling.

Maclurin [(3,4-dihydroxyphenyl)-(2,4,6-trihydroxyphenyl) methanone] is a natural compound that can be extracted from white mulberry(Morus alba) and purple mangosteen(Garcinia mangostana). Maclurin is known for its dual-sided effect on reactive oxygen species (ROS). Osteosarcoma is a primary malignant tumor of the bone and is one of the most aggressive cancers. It is common especially in children and young adults and can progress into highly metastatic cancer. In this study, we investigated the anti-cancer effects of maclurin on U2OS human osteosarcoma cells. The results indicated that maclurin exerts prooxidative effects and induces apoptosis via capase-3-independent PARP regulation in U2OS human osteosarcoma cells. Maclurin also inhibits the migration of U2OS human osteosarcoma cells. Maclurin modulates two of the three major mitogen-activated protein kinases that are closely linked with cancer metastasis; that is, it activates p38 and inactivates Extracellular signal-regulated kinase. The apoptosis-inducing effects of maclurin on U2OS osteosarcoma cells were diminished by additional treatment with antioxidant N-acetyl cysteine (NAC), but the migration-inhibiting effect was not affected by NAC treatment. This further suggested the only apoptosis-inducing effect of maclurin may be strongly related to its prooxidative activity. Taken together, these results suggested that maclurin may be a strong candidate molecule as an anti-osteosarcoma agent.

Nigella and Milk Thistle Seed Oils: Potential Cytoprotective Effects against 7β-Hydroxycholesterol-Induced Toxicity on SH-SY5Y Cells.

Oxysterols are assumed to be the driving force behind numerous neurodegenerative diseases. In this work, we aimed to study the ability of 7β-hydroxycholesterol (7β-OHC) to trigger oxidative stress and cell death in human neuroblastoma cells (SH-SY5Y) then the capacity of Nigella sativa and Milk thistle seed oils (NSO and MTSO, respectively) to oppose 7β-OHC-induced side effects. The impact of 7β-OHC, associated or not with NSO or MTSO, was studied on different criteria: cell viability; redox status, and apoptosis. Oxidative stress was assessed through the intracellular reactive oxygen species (ROS) production, levels of enzymatic and non-enzymatic antioxidants, lipid, and protein oxidation products. Our results indicate that 7β-OHC (40 µg/mL) exhibit pr-oxidative and pro-apoptotic activities shown by a decrease of the antioxidant enzymatic activities and an increase of ROS production, lipid, and protein oxidation end products as well as nitrotyrosine formation and caspase 3 activation. However, under the pre-treatment with NSO, and especially with MTSO (100 µg/mL), a marked attenuation of oxidative damages was observed. Our study suggests harmful effects of 7β-OHC consisting of pro-oxidative, anti-proliferative, and pro-apoptotic activities that may contribute to neurodegeneration. NSO and especially MTSO showed potential cytoprotection against the cytotoxicity of 7β-OHC.

Bioactivity of Humic Acids Extracted From Shale Ore: Molecular Characterization and Structure-Activity Relationship With Tomato Plant Yield Under Nutritional Stress.

The increasing demands for biostimulants in the agricultural market over the last years have posed the problem of regulating this product category by requiring the industry to make available the information about efficacy and safety, including the explanation of mode of action and the definition of bioactive constituents. In the present study, we tested the biostimulant proprieties of a sedimentary shale ore-extracted humic acid (HA) on Micro Tom tomato plants under increasing nutritional stress and investigated the correlation with the chemical features of HA by means of ultra-high resolution FT-ICR MS, FT-ATR, and 13C-NMR. Humic acid application proved effective in alleviating the nutritional stress by improving nutrient use efficiency, with results comparable to the control treatment supplied with higher NPK nutrition. Increased yield (up to +19%) and fruit quality (in the range +10–24%), higher ascorbic acid content and a better root growth were the main parameters affected by HA application. Molecular-level characterization identified the possible chemical drivers of bioactivity, and included flavonoids, quinones, and alkaloids among the most represented molecules, some of which exhibiting antioxidant, pro-oxidant, and antimicrobial activity. The redox effect was discussed as a determinant of the delicate homeostasis balance, capable of triggering plant defense response and eventually inducing a protective priming effect on the plants.

Ability of Sodium Dodecyl Sulfate (SDS) Micelles to Increase the Antioxidant Activity of α-Tocopherol.

As emulsifiers become saturated on the surface of an emulsion droplet, any additional emulsifier migrates to the aqueous phase. Continuous phase surfactants have been shown to increase α-tocopherol efficacy, but it is unclear if this is the result of chemical or physical effects. The addition of α-tocopherol to an oil-in-water emulsion after homogenization resulted in a 70% increase of α-tocopherol in the continuous phase when sodium dodecyl sulfate (SDS) was at levels that were greater than the SDS critical micelle concentration. Conversely, when α-tocopherol was dissolved in the lipid before emulsification, continuous phase SDS concentrations did not increase. When SDS concentration led to an increase in the aqueous phase α-tocopherol, the oxidative stability of oil-in-water emulsions increased. Data indicated that the increased antioxidant activity was the result of surfactant micelles being able to decrease the prooxidant activity of α-tocopherol. Considering these results, surfactant micelles could be an important tool to increase the effectiveness of α-tocopherol.

Evaluation of Antimicrobial, Antioxidant, and Cytotoxic Activity of Phenolic Preparations of Diverse Composition, Obtained from Elaeagnus rhamnoides (L.) A. Nelson Leaf and Twig Extracts.

Although the major components of various organs of sea buckthorn have been identified (particularly phenolic compounds), biological properties of many of these phytochemicals still remain poorly characterized. In this study, we focused on the chemical composition and biological activity of preparations that were obtained from sea buckthorn twigs and leaves. The objective was to investigate cytotoxicity of these preparations against human fibroblast line HFF-1, using MTT reduction assay, their anti- or pro-oxidant activities against the effects of a biological oxidant -H2O2/Fe—on human plasma lipids and proteins in vitro (using TBARS and carbonyl groups as the markers of oxidative stress). Antimicrobial activity of the tested preparations against Gram-positive (Staphylococcus aureus, S. epidermidis, Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), as well as against fungi (Candida albicans, C. glabrata) by the EUCAST-approved broth microdilution method, followed by growth on solid media, were also assessed. Our analysis showed significant differences in chemical composition and biological properties of the tested preparations (A–F). All tested preparations from sea buckthorn twigs (D–F) and one preparation from sea buckthorn leaves (preparation C) may be a new source of phenolic antioxidants for pharmacological and cosmetic applications.

Characteristics of hemoglobin and its pro‐oxidative activity in washed silver carp ( Hypophthalmichthys molitrix ) mince as affected by pH

The objectives of this study were to investigate the pro-oxidative activity of hemoglobin and its effect on lipid and protein oxidation changes in silver carp washed mince over 12 days of storage at 4°C under different pHs (6.0, 6.5, 7.0, 7.5, 8.0). The results suggested that the formation of Methemoglobin decreased the relative oxygenation of hemoglobin in acidic pH (6, 6.5) as compared to neutral or alkaline pH (7, 7.5, and 8.0). Hemoglobin promoted lipid oxidation more effectively under acidic conditions (pH 6.0) rather than alkaline pH (8.0), as indicated by the higher peroxide values and thiobarbituric acid-reactive substances. Moreover, hemoglobin was found to be more conducive in initiating protein oxidation by increasing the carbonyl and dimeric tyrosine content while decreased the total sulfhydryl content in washed mince system under acidic conditions, which was linked to a higher auto-oxidation rate. These results suggested that the lipid and protein oxidation in fish mince were more likely mediated by hemoglobin, whose pro-oxidative activity could be influenced by its pH level. Practical applications This study demonstrates that hemoglobin pro-oxidative activity is mainly affected by pH. The shift of pH from acidic to alkaline could attenuate hemoglobin autoxidation. This work provides a means to slow down lipid and protein oxidation during storage of fish mince by adjusting to slightly alkaline pH, which could maintain the freshwater fish mince quality.

Clinical efficiency of antioxidant therapy in patients with liver cirrhosis and acute blood loss

Objective:to determine the clinical efficiency of antioxidant therapy in patients with liver cirrhosis and acute blood loss.Material and methods.The study included 286 patients with liver cirrhosis and acute blood loss of varying degrees of severity. The patients were divided into two series of studies. In the first series, the patients received the therapy according to the clinical diagnostic and treatment protocols, in the second series 1 according to the same protocols in combination with an intravenous administration of the antioxidant complexes “Reamberin” and “Fluimucil”. After 48 hours from admission, the antioxidant status of blood serum, the blebbing index of lymphocytes, the concentration of uric acid, and the level of hemoglobin were analyzed. The indicators of the clinical efficiency of the treatment were determined: risk of absolute mortality, risk of relative mortality, the number needed to treat.Results.The blood serum of the patients from the first series of studies was characterized by pronounced prooxidant activity, high values of the lymphocyte blebbing index, and a small amount of uric acid, which was indicative of the development of oxidative stress. The mortality rate in this series of studies was 26.0 %. The patients of the second series of studies were characterized by pronounced antioxidant activity of blood serum, low values of the lymphocyte blebbing index, and high concentrations of uric acid, which indicated a decrease in the activity of systemic oxidation processes. The mortality rate in this series of studies was 18.2 %. The duration of the treatment decreased from 16.5 days (first series) to 13.0 days (second series).Conclusion.The combined use of the “Reamberin” and “Fluimucil” complexes as part of the therapy according to the clinical diagnostic and treatment protocols leads to a relief of oxidative stress in patients with liver cirrhosis complicated by acute blood loss. The blood serum of these patients is characterized by pronounced antioxidant activity, low values of the lymphocyte blebbing index, and a high concentration of uric acid, which reduces the risk for the development of multiple organ failure syndrome. This therapy decreases the mortality rate to 18.2 % and the duration of the treatment to 13.0 days.