Free Reactive Oxygen Species Research Articles

Free Radical Generation in Far-UV Synchrotron Radiation Circular Dichroism Assays-Protein and Buffer Composition Contribution.

A useful tool to analyze the ligands and/or environmental contribution to protein stability is represented by the Synchrotron Radiation Circular Dichroism UV-denaturation assay that consists in the acquisition of several consecutive repeated far-UV SRCD spectra. Recently we demonstrated that the prevailing mechanism of this denaturation involves the generation of free radicals and reactive oxygen species (ROS). In this work, we analyzed the effect of buffering agents commonly used in spectroscopic measurements, including MOPS (3-(N-morpholino) propanesulfonic acid), HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), TRIS-HCl (tris-hydroxymethil aminomethane hydrochloride), and phosphate, on the efficiency of protein denaturation caused by exposure to UV radiation. Fluorescence experiments confirmed the presence of ROS and were used to determine the rate of ROS generation. Our results indicate that the efficiency of the denaturation process is strongly influenced by the buffer composition with MOPS and HEPES acting also as scavengers and that the presence of proteins itself influenced the ROS formation rate.

Profiling cosmeceutical effects of various herbal extracts through elastase, collagenase, tyrosinase inhibitory and antioxidant assays

• Cotinus coggygria is one of the plant species in terms of cosmeceutical effect. • Active plant species usually have records against skin disorders. • Use of active extracts with different antioxidant mechanisms will be more effective. Plants have been a very rich resource for the development of potentially new drug candidates and also the development of cosmetic products for skincare. The skin produces free radicals or reactive oxygen species through repeated exposure to the sun and these molecules cause oxidative stress and inflammatory reactions in the dermal and epidermal layers of the skin. Matrix metalloproteinases are triggered by aging and in inflamed skin, such as photo-aged skin, skin damage, and wrinkles occurred by collapsing dermal proteins such as collagen and elastin. In the development of plant-based skin whitening products, the first target is to investigate the inhibitors of the tyrosinase enzyme, which provides melanin production. The ethanol extracts of 92 herbal extracts and propolis were tested for their elastase, collagenase, and tyrosinase inhibitory effects using ELISA microtiter assays. Their antioxidant effect was determined using DPPH, DMPD, and NO radical scavenging activity, metal-chelation capacity, FRAP, PRAP, and CUPRAC assays. Total phenolic and flavonoid contents of the extracts were also determined spectrophotometrically. Our results from the screening studies showed that the ethanol extracts prepared from the aerial parts of Lamium purpureum subsp. purpureum, the pericarpium of Garcinia mangostana and Pistacia vera , the flowers of Punica granatum, and the seeds of Vitis vinifera were effective against at least two of these enzymes and therefore, the plant species were selected for further studies.

Autophagy, TERT, and mitochondrial dysfunction in hyperoxia.

Ventilation with gases containing enhanced fractions of oxygen is the cornerstone of therapy for patients with hypoxia and acute respiratory distress syndrome. Yet, hyperoxia treatment increases free reactive oxygen species (ROS)-induced lung injury, which is reported to disrupt autophagy/mitophagy. Altered extranuclear activity of the catalytic subunit of telomerase, telomerase reverse transcriptase (TERT), plays a protective role in ROS injury and autophagy in the systemic and coronary endothelium. We investigated interactions between autophagy/mitophagy and TERT that contribute to mitochondrial dysfunction and pulmonary injury in cultured rat lung microvascular endothelial cells (RLMVECs) exposed in vitro, and rat lungs exposed in vivo to hyperoxia for 48 h. Hyperoxia-induced mitochondrial damage in rat lungs [TOMM20, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)], which was paralleled by increased markers of inflammation [myeloperoxidase (MPO), IL-1β, TLR9], impaired autophagy signaling (Beclin-1, LC3B-II/1, and p62), and decreased the expression of TERT. Mitochondrial-specific autophagy (mitophagy) was not altered, as hyperoxia increased expression of Pink1 but not Parkin. Hyperoxia-induced mitochondrial damage (TOMM20) was more pronounced in rats that lack the catalytic subunit of TERT and resulted in a reduction in cellular proliferation rather than cell death in RLMVECs. Activation of TERT or autophagy individually offset mitochondrial damage (MTT). Combined activation/inhibition failed to alleviate hyperoxic-induced mitochondrial damage in vitro, whereas activation of autophagy in vivo decreased mitochondrial damage (MTT) in both wild type (WT) and rats lacking TERT. Functionally, activation of either TERT or autophagy preserved transendothelial membrane resistance. Altogether, these observations show that activation of autophagy/mitophagy and/or TERT mitigate loss of mitochondrial function and barrier integrity in hyperoxia.NEW & NOTEWORTHY In cultured pulmonary artery endothelial cells and in lungs exposed in vivo to hyperoxia, autophagy is activated, but clearance of autophagosomes is impaired in a manner that suggests cross talk between TERT and autophagy. Stimulation of autophagy prevents hyperoxia-induced decreases in mitochondrial metabolism and sustains monolayer resistance. Hyperoxia increases mitochondrial outer membrane (TOMM20) protein, decreases mitochondrial function, and reduces cellular proliferation without increasing cell death.

The involvement of TRPV4 on the hypoxia-induced oxidative neurotoxicity and apoptosis in a neuronal cell line: Protective role of melatonin

The hypoxia (HYPX)-mediated excessive generation of mitochondrial free reactive oxygen species (mROS) and the overload Ca2+ influx via the inhibition of TRPV4 are controlled by the treatment of antioxidants. However, the molecular mechanisms underlying melatonin (MLT)'s neuroprotection remains elusive. We investigated the role of MLT via modulation of TRPV4 on oxidative neurodegeneration and death in SH-SY5Y neuronal cells. The SH-SY5Y cells were divided into five groups as follows: control, MLT (1 mM for 2 h), HYPX (200 μM CoCl2 for 24 h), HYPX + MLT, and HYPX + TRPV4 blockers (ruthenium red-1 μM for 30 min). The HYPX caused to the increase of TRPV4 current density and overload Ca2+ influx with an increase of mitochondrial membrane potential and mROS generation. The changes were not observed in the absence of TRPV4. When HYPX exposure and TRPV4 agonist (GSK1016790A)-induced TRPV4 activity were inhibited by the treatment of ruthenium red or MLT, the increase of mROS, lipid peroxidation, apoptosis, Zn2+ concentrations, TRPV4, caspase -3, caspase -9, Bax, and Bcl-2 expressions were restored via upregulation of reduced glutathione, glutathione peroxidase, and total antioxidant status. The levels of apoptosis and cell death in the cells were enriched with increases of caspase -3 and -9 activations, although they were decreased by MLT treatment. In conclusion, the treatment of MLT modulates HYPX-mediated mROS, apoptosis, and TRPV4-mediated overload Ca2+ influx and may provide an avenue for protecting HYPX-mediated neurological diseases associated with the increase of mROS, Ca2+, and Zn2+ concentration.

Selenium nanoparticles reduced cadmium uptake, regulated nutritional homeostasis and antioxidative system in Coriandrum sativum grown in cadmium toxic conditions

Nanotechnology has become a valuable novel approach to manage several environmental challenges through providing innovative and effective solutions. Heavy metal stress is an important abiotic limiting factor. Seed priming with selenium (Se) alleviates various kinds of environmental stresses; yet, the potential of seed priming with selenium nanoparticles (SeNPs) under cadmium (Cd) stress for coriander crop has never been evaluated. This research work was designed to explore the effects of seed priming with three levels (0, 5, 10 and 15 mg L−1) of SeNPs solution on the physio-biochemical characteristics, nutrition, antioxidative defense system and growth of coriander under Cd stress. Cadmium toxicity reduced chlorophyll content, photosynthetic activity and growth of treated plants. Moreover, Cd stressed plants exhibited modulations in proline level, together with decreased water potential, and leaf osmotic potential. However, SeNPs increased growth attributes, chlorophyll content, total soluble sugars, leaf relative water content, and gas exchange parameters in treated plants which were conversely decreased by Cd toxicity. The seeds priming with SeNPs promoted antioxidant response by increasing catalase (CAT), ascorbate peroxidase (APX) and peroxidase (POX) activity and safeguarding cellular structures through scavenging free radicals and reactive oxygen species. Furthermore, Cd stressed plants displayed an upper level of MDA (1.91 fold) while SeNPs improved membranous integrity through detoxification of hydrogen peroxide. Additionally, SeNPs enhanced nutrients contents (P, K, Ca, Mg, Zn), metal tolerance index and diminished Cd content in plants resulting in the improved growth and development of Cd affected coriander plants.

Modern Medicines (Assortment) and Trends in the Improvement of Dosage Forms of Hepatoprotective Agents (Review)

Introduction. Liver diseases with all the variety of clinical manifestations have common pathogenetic links at the cellular level. The group of hepatoprotective agents is represented by drugs that exhibit versatile mechanisms for protecting liver cells from the effects of damaging factors, the main of which are membrane-stabilizing, antioxidant, regenerative, detoxifying, choleretic and anti-inflammatory effects. The high therapeutic and hepatoprotective effectiveness of modern drugs is largely due to their metabolic effects, as well as their ability to bind free radicals and reactive oxygen species in the cell.Text. The purpose of this work is to form an analytical review of the literature on the assortment and concepts of improving the dosage forms of hepatoprotective agents. According to the analysis and systematization of modern publications devoted to the use of hepatoprotectors in the treatment of liver diseases, it is shown that it is necessary to develop new formulations and combinations of biologically active substances with the manifestation of versatile mechanisms of hepatoprotection, as well as to improve the composition and manufacturing technologies of existing traditional therapies. One of the current trends is the use of new substances in the development of traditional and innovative dosage forms. The search for biologically active molecules with antioxidant, antiradical and membrane-stabilizing activity that can be considered as effective hepatoprotectors continues. An integral task of pharmaceutical development is the creation of bioavailable drugs that have a prolonged effect and minimal side effects. A promising direction in pharmaceutical technology is the development of innovative drugs for the directed transport of biologically active molecules to the affected organ.Conclusion. As a result of the analysis of modern data, priority directions for the development and improvement of existing formulations based on modern approaches to the production of innovative dosage forms are identified. The relevance of improving the dosage forms of hepatoprotectors presented on the pharmaceutical market is shown. Of particular interest is the development of innovative targeted delivery systems with effective and safe hepatoprotectors in various combinations, including those based on cinnamic acid derivatives.

Do biomarkers allow a differentiation between osteonecrosis of the femoral head and osteoarthritis of the hip? – a biochemical, histological and gene expression analysis

Osteonecrosis of the femoral head (ONFH) is a devastating disease of the hip joint. Its early diagnosis is crucial to increase the chances of joint preserving, yet difficult due to similarities with osteoarthritis (OA) of the hip in its clinical appearance. The purpose of this study was to enhance the understanding of ONFH and its pathologic processes in contrast to OA and to identify serum biomarkers helping to improve the diagnosis of the disease. Bone and bone marrow samples were collected from 24 patients diagnosed with OA and 25 patients with ONFH during total hip replacement surgery. RNA was isolated, histological examination, determination of free reactive oxygen species as well as gene expression and biomarker analysis were performed. Histological analysis revealed differences in the structural and cellular pattern between the groups. Gene expression analysis revealed a significant upregulation for the genes ASPN, COL1A1, COL2A1 and IL6 and a significant downregulation for HIF1A in ONFH compared to OA group. Analysis of serum biomarkers showed significant differences between the groups for asporin and adiponectin. A final logistical regression model including the parameters adiponectin, asporin and HIF 1α was overall significant, explained 34.5 % of variance and classified 74.5 % of the cases correctly. The combination of adiponectin, asporin and HIF 1α as serum biomarkers revealed a classification accuracy of 74.5 %. The information provided in this study may help to enhance the understanding of pathologic processes in ONFH and to elaborate further aspects of prediction and treatment.

Targeting Pro-Oxidant Iron with Deferoxamine as a Treatment for Ischemic Stroke: Safety and Optimal Dose Selection in a Randomized Clinical Trial.

A role of iron as a target to prevent stroke-induced neurodegeneration has been recently revisited due to new evidence showing that ferroptosis inhibitors are protective in experimental ischemic stroke and might be therapeutic in other neurodegenerative brain pathologies. Ferroptosis is a new form of programmed cell death attributed to an overwhelming lipidic peroxidation due to excessive free iron and reactive oxygen species (ROS). This study aims to evaluate the safety and tolerability and to explore the therapeutic efficacy of the iron chelator and antioxidant deferoxamine mesylate (DFO) in ischemic stroke patients. Administration of placebo or a single DFO bolus followed by a 72 h continuous infusion of three escalating doses was initiated during the tPA infusion, and the impact on blood transferrin iron was determined. Primary endpoint was safety and tolerability, and secondary endpoint was good clinical outcome (clinicalTrials.gov NCT00777140). DFO was found safe as adverse effects were not different between placebo and DFO arms. DFO (40–60 mg/Kg/day) reduced the iron saturation of blood transferrin. A trend to efficacy was observed in patients with moderate-severe ischemic stroke (NIHSS > 7) treated with DFO 40–60 mg/Kg/day. A good outcome was observed at day 90 in 31% of placebo vs. 50–58% of the 40–60 mg/Kg/day DFO-treated patients.

26977 Synergistic blend of green tea and lotus protects against blue light-induced free radicals

Background: Growing evidence suggests that blue light emission stemming from solar irradiation and electronic devices, including computer screens, tablets and smartphones, has an effect on the molecular mechanism of premature photoaging. Exposure to blue light induces the generation of free radicals and reactive oxygen species (ROS) that cause inflammation and extrinsic skin aging. Quenching and scavenging free radicals can help mitigate and prevent signs of skin damage. We developed a patent-pending, nature-based blend of green tea and lotus that demonstrated a synergistic skin health benefit using DPPH assay.

Evaluation of Antioxidant activities of Aqueous extract from Bryophyllum pinnatum on Carbon tetrachloride-induced albino rat tissues

Oxidative injury or cellular damage arising from free radicals or reactive oxygen species (ROS) has been implicated in the pathogenesis of many human diseases. These ROS are generated through normal metabolism of drugs, environmental chemicals and other xenobiotics as well as endogenous chemicals. Accumulated evidence suggests that ROS can be scavenged through chemoprevention utilizing natural antioxidant compounds present in foods and medicinal plants. The aim of this study is to evaluate antioxidant activities of aqueous extract of Bryophyllum pinnatum using carbon tetrachloride-induced albino rats as model. An in-vivo antioxidant activity was carried out on the CCl4 induced rats by administration of aqueous extract of Bryophyllum pinnatum at doses of 50, 100 and 200mg/Kg bw for 14 consecutive days, and one group was treated with Silymarin at a dose of 50 mg/Kg as a standard drug. The antioxidant activities were estimated by evaluating its effects on antioxidant parameters in the tissues of albino rats (Serum, Liver and Heart). The activity of catalase (CAT), Superoxide dismutase (SOD), Glutathione peroxidase (GPx) and the levels of MDA and GSH were evaluated in tissue homogenates. Results showed that the rats fed with the higher concentrations of Bryophyllum pinnatum had significant increase (p<0.05) in glutathione content (GSH), GPx, SOD and catalase activities relative to normal and standard control. However, the level of MDA was decreased (p<0.05) for the treated groups (100 and 200mg/kg). These results suggest that aqueous extracts of Bryophyllum pinnatum has active substances contributing to varied degrees of potent antioxidant activity and could serve as important source of antioxidants in food, cosmetics and pharmaceutical industries.
 Keywords: Oxidative injury, Bryophyllum pinnatum, antioxidant, Diseases, Tissues

Superiority of modified graphene oxide for enhancing the growth, yield, and antioxidant potential of pearl millet (Pennisetum glaucum L.) under salt stress

Soil salinity is a serious global problem that affects the vegetative growth and photosynthesis rates of plants. Additionally, a high salinity facilitates the accumulation of free radicals and reactive oxygen species (ROS), which induces an increase in the malondialdehyde, hydrogen peroxide, and proline contents, and a decrease in the antioxidant activity of enzymes, such as superoxide dismutase and peroxidase, reducing the fodder yield. Owing to limited availability of forage crops, extensive efforts have been devoted to studying the pearl millet (Pennisetum glaucum L.) plant, which is employed as a protein-rich fodder crop in its green and dry forms. Therefore, a field experiment was conducted to explore the effect of graphene oxide, methionine, lysine, methionine@graphene oxide, and lysine@graphene oxide on the growth, biomass accumulation, photosynthetic pigment content, total protein content, oxidative stress, and antioxidant response of the pearl millet plant. Modified graphene oxide (20 mg L−1) was applied two times to the fresh leaves of pearl millet after 30 and 60 days of cultivation. The salt concentrations in the soil and water in the area under consideration were 3.16 d.Sm−1 and 10.29 d.Sm−1, respectively. The treatments induced a significant improvement in plant growth, biomass accumulation, total protein content, photosynthetic pigment content, and yield. Similarly, the generation of ROS was reduced in the plant cells/tissues compared to the case in the plants grown under saline conditions. The foliar application of both graphene oxide and its modified structures enhanced the salinity stress tolerance of pearl millet by modulating its morphological and biophysical traits. This study offers new possibilities for the application of modified materials in agriculture and provides a valuable basis for improving plant tolerance and adaptability to salinity stress.

Sera from patients with tuberculosis increase the phagocytic-microbicidal activity of human neutrophils, and ESAT-6 is implicated in the phenomenon.

It has been reported that sera from patients with active pulmonary tuberculosis (APT) induced nuclear changes in normal neutrophils that included pyknosis, swelling, apoptosis, and production of extracellular traps (NETs). Similar changes were observed with some sera from their household contacts but not with sera from healthy, unrelated individuals. It was suggested that those sera from household contacts that induced neutrophil nuclear changes might correspond to people with subclinical tuberculosis. Thus, our experimental approach might serve to identify individuals with early, ongoing disease. Nuclear changes in neutrophils were fully evident by 3 h of contact and beyond. Circulating mycobacterial antigens were the most likely candidates for this effect. We wanted to know whether the nuclear changes induced on neutrophils by the sera of APT patients would negatively affect the phagocytic/microbicidal ability of neutrophils exposed to APT sera for short periods. We now provide evidence that short-term contact (30 min) with sera from patients with pulmonary tuberculosis increases several phagocytic parameters of normal neutrophils, including endocytosis, myeloperoxidase levels, production of free reactive oxygen species, phagolysosome fusion, and microbicidal activity on Staphylococcus aureus, with these effects not being observed with sera from healthy donors. We also give evidence that suggests that ESAT-6 and CFP-10 are involved in the phenomenon. We conclude that activation is a stage that precedes lethal nuclear changes in neutrophils and suggests that autologous neutrophils must circulate in an altered state in the APT patients, thus contributing to the pathology of the disease.

Free Radicals and ROS Induce Protein Denaturation by UV Photostability Assay.

Oxidative stress, photo-oxidation, and photosensitizers are activated by UV irradiation and are affecting the photo-stability of proteins. Understanding the mechanisms that govern protein photo-stability is essential for its control enabling enhancement or reduction. Currently, two major mechanisms for protein denaturation induced by UV irradiation are available: one generated by the local heating of water molecules bound to the proteins and the other by the formation of reactive free radicals. To discriminate which is the likely or dominant mechanism we have studied the effects of thermal and UV denaturation of aqueous protein solutions with and without DHR-123 as fluorogenic probe using circular dichroism (CD), synchrotron radiation circular dichroism (SRCD), and fluorescence spectroscopies. The results indicated that the mechanism of protein denaturation induced by VUV and far-UV irradiation were mediated by the formation of reactive free radicals (FR) and reactive oxygen species (ROS). The development at Diamond B23 beamline for SRCD of a novel protein UV photo-stability assay based on consecutive repeated CD measurements in the far-UV (180–250 nm) region has been successfully used to assess and characterize the photo-stability of protein formulations and ligand binding interactions, in particular for ligand molecules devoid of significant UV absorption.

Chemical composition, antioxidant activities and antibacterial activities of essential oil from Erythrina caffra Thunb. growing in South Africa

IntroductionEssential oils from plants are recognized as one of the most promising secondary metabolites for the development of cheap and safer drugs. While Erythrina caffra has been prominently used in folk medicine for the treatment of microbial infections, there is dearth of information on the pharmacological effectiveness and chemical composition of its essential oil. The study, therefore, aimed at identifying the chemical composition and biological activities of the essential oil of Erythrina caffra. MethodsIn this study, the essential oil was extracted with all-glass Clevenger. The antioxidant activities of the essential oil and antibacterial susceptibility assay by agar well diffusion techniques were assessed while GC-MS analysis was performed to identify the chemical constituents of the essential oil. ResultsThe study showed that the radical scavenging activity of the essential oil increases as the concentration of the essential oil increases. All bacterial isolates were susceptible to essential oil with the exception of Salmonella typhimurium and Pseudomonas aeruginosa producing inhibition zones ranging between 22 ± 1.3 and 35 ± 2.1 mm in the susceptible isolates. The GC-MS chromatogram indicated there are 35 bioactive compounds in the essential oil and Caryophyllene oxide (53.54%), [1S-(1α,7α,8aβ)]-1,2,3,5,6,7,8,8a-octa-1 - hydro-1,8a-dimethyl-7-(1-methylethenyl)-Naphthalene (7.81%), Kauran-18-al (6.49%), 10,10-Dimethyl-2,6-dimethylenebicy clo[7.2.0]undecan-5.beta.-ol (5.83%), 10s,11s-Himachala-3(12),4-diene (4.51%), Caryophyllene (3.65%) and 1- Hexanol (3.31%) were the most prominent compounds. ConclusionExcessive production of free radicals or reactive oxygen species (ROS) causes oxidative stress and disease. Oxidative stress resulting from imbalance between excessive generation of free radicals and inadequate antioxidant defense system has been linked to pathogenesis of many diseases. The essential oil of E. caffra stem bark extract possess antimicrobial and good antioxidant activities and its rich level of phytochemicals can be used as either dietary or complementary agents.

Testosterone, cortisol, vitamin D and oxidative stress and their relationships in professional soccer players.

The testosterone/cortisol ratio has been used in sport physiology to evaluate the balance between anabolism and catabolism; its decrease below 30% has been considered a marker of overtraining. In this framework recent studies in soccer players have investigated the relationships between testosterone, cortisol, vitamin D and reactive oxygen species, but with unconvincing results. The aim of the present study was to evaluate the behavior of such biological parameters and their relationships both in winter (the season of championship) and in summer (off-competition season), characterized by different homeostatic situations. Twenty-seven professional male football players (Second Italian Division), were studied. Blood levels of free testosterone, cortisol, vitamin D and reactive oxygen species were evaluated in August (pre-season training) and in February, in the midseason. A comparison between these two periods was performed and for each of them the relationships between the biological parameters were evaluated. Blood levels of testosterone were higher during summer whereas those of cortisol were higher in winter. Vitamin D levels were higher in summer; in this season a positive significant relationship between vitamin D and testosterone was observed (P=0.001), but not in winter (P=0.592). Reactive oxygen species were higher in winter; in this season a significant positive relationship between these substances and cortisol was observed (0.000), but not in summer (P=0.325). In professional soccer players it was found a positive relationship between vitamin D and testosterone in summer and between reactive oxygen species and cortisol in winter. However, the question whether such results are genuine cause-effect relationships or mere casual or spurious statistical correlations is still unsolved. As matter of fact, such results could be dependent from other determinants which might drive the aforementioned biological parameters in the same direction. These conclusions must be considered valid only in relation to the experimental conditions (training workload, diet and sun exposure) of the present study.

Low Doses of Gamma Irradiation Stimulate Synthesis of Bioactive Compounds with Antioxidant Activity in Fomes fomentarius Living Mycelium

Environmental changes generate free radicals and reactive oxygen species (ROS), resulting in abiotic stress in plants and fungi. Gamma ionizing radiation generates a significant amount of free radicals and ROS, thereby simulating natural environmental stressors. We used a 60Co source of radiation to experimentally induce oxidative stress in living mycelium mass of the medicinal fungus Fomes fomentarius, in order to obtain a late response of stress tolerance by means of bioactive compounds synthesis. We measured the response at 24, 48, and 72 h after the irradiation. The highest improvement was found 24 h after exposure for antioxidant activity and for total phenolic compounds of methanolic extract, with a 1.89- and 1.64-fold increase, respectively. The total flavonoids in methanolic extract increased 1.68 times after 48 h from treatment and presented a more stable raising in the assessed time-lapse. For the three analyzed parameters, 300 Gy was the optimum absorbed dose to trigger a beneficial response, with potentially applications in pharmaceutics and nutraceutics. Gamma irradiation can be used as a biotechnological tool to direct the secondary metabolites synthesis upregulation in medicinal mushroom living mycelium.

The Role of NADPH Oxidase in Neuronal Death and Neurogenesis after Acute Neurological Disorders.

Oxidative stress is a well-known common pathological process involved in mediating acute neurological injuries, such as stroke, traumatic brain injury, epilepsy, and hypoglycemia-related neuronal injury. However, effective therapeutic measures aimed at scavenging free reactive oxygen species have shown little success in clinical trials. Recent studies have revealed that NADPH oxidase, a membrane-bound enzyme complex that catalyzes the production of a superoxide free radical, is one of the major sources of cellular reactive oxygen species in acute neurological disorders. Furthermore, several studies, including our previous ones, have shown that the inhibition of NADPH oxidase can reduce subsequent neuronal injury in neurological disease. Moreover, maintaining appropriate levels of NADPH oxidase has also been shown to be associated with proper neurogenesis after neuronal injury. This review aims to present a comprehensive overview of the role of NADPH oxidase in neuronal death and neurogenesis in multiple acute neurological disorders and to explore potential pharmacological strategies targeting the NADPH-related oxidative stress pathways.

Ferulago angulata as a Good Radioprotector Against Genotoxicity.

Natural products can be used as radioprotector agents because of containing phenolic compounds and several flavonoids with antioxidant properties. When the normal cells are exposed to ionizing radiation, they generate free radicals and reactive oxygen species that can cause damage in DNA, which leads to cellular dysfunction or even cell death. However, it is necessary to identify new radioprotective agents to protect normal cells. Ferulago angulata (F. angulata), a medicinal plant, can be used as a new radioprotective agent. In this study, the radioprotective effect of F. angulata was evaluated against genotoxicity and oxidative stress induced by ionizing radiation in human blood lymphocytes. The antioxidant activity of F. angulata was assayed using FRAP and DPPH methods. Then, the human blood samples were incubated with F. angulata at different concentrations (25, 50, 100, and 200 μM) and subsequently exposed to IR at a dose of 2Gy. The radioprotective effect of F. angulata on the exposed cells was assessed by the micronucleus (MN) method. Also, biomarkers of oxidative stress in the exposed cells were evaluated by malondialdehyde (MDA) and superoxide dismutase (SOD) methods. Our findings showed that F. angulata reduced the frequency of MN induced by IR in exposed cells. At a 200 μM concentration of F. angulata, the maximum reduction in the frequency of MN (63.11%) was observed that demonstrated a high degree of radioprotection. Afterward, pretreatment at 200 μM concentration of F. angulata inhibited oxidative stress in irradiated lymphocytes, leading to a reduction in MN frequency and MDA levels while SOD activity was enhanced in the exposed cells. F. angulata as a natural radioprotective agent can protect normal cells against reactive oxygen species and genetic damage induced by IR.

Cerium Oxide Nanoparticles: A New Therapeutic Tool in Liver Diseases.

Oxidative stress induced by the overproduction of free radicals or reactive oxygen species (ROS) has been considered as a key pathogenic mechanism contributing to the initiation and progression of injury in liver diseases. Consequently, during the last few years antioxidant substances, such as superoxide dismutase (SOD), resveratrol, colchicine, eugenol, and vitamins E and C have received increasing interest as potential therapeutic agents in chronic liver diseases. These substances have demonstrated their efficacy in equilibrating hepatic ROS metabolism and thereby improving liver functionality. However, many of these agents have not successfully passed the scrutiny of clinical trials for the prevention and treatment of various diseases, mainly due to their unspecificity and consequent uncontrolled side effects, since a minimal level of ROS is needed for normal functioning. Recently, cerium oxide nanoparticles (CeO2NPs) have emerged as a new powerful antioxidant agent with therapeutic properties in experimental liver disease. CeO2NPs have been reported to act as a ROS and reactive nitrogen species (RNS) scavenger and to have multi-enzyme mimetic activity, including SOD activity (deprotionation of superoxide anion into oxygen and hydrogen peroxide), catalase activity (conversion of hydrogen peroxide into oxygen and water), and peroxidase activity (reducing hydrogen peroxide into hydroxyl radicals). Consequently, the beneficial effects of CeO2NPs treatment have been reported in many different medical fields other than hepatology, including neurology, ophthalmology, cardiology, and oncology. Unlike other antioxidants, CeO2NPs are only active at pathogenic levels of ROS, being inert and innocuous in healthy cells. In the current article, we review the potential of CeO2NPs in several experimental models of liver disease and their safety as a therapeutic agent in humans as well.

The Mystery of Red Blood Cells Extracellular Vesicles in Sleep Apnea with Metabolic Dysfunction

Sleep is very important for overall health and quality of life, while sleep disorder has been associated with several human diseases, namely cardiovascular, metabolic, cognitive, and cancer-related alterations. Obstructive sleep apnea (OSA) is the most common respiratory sleep-disordered breathing, which is caused by the recurrent collapse of the upper airway during sleep. OSA has emerged as a major public health problem and increasing evidence suggests that untreated OSA can lead to the development of various diseases including neurodegenerative diseases. In addition, OSA may lead to decreased blood oxygenation and fragmentation of the sleep cycle. The formation of free radicals or reactive oxygen species (ROS) can emerge and react with nitric oxide (NO) to produce peroxynitrite, thereby diminishing the bioavailability of NO. Hypoxia, the hallmark of OSA, refers to a decline of tissue oxygen saturation and affects several types of cells, playing cell-to-cell communication a vital role in the outcome of this interplay. Red blood cells (RBCs) are considered transporters of oxygen and nutrients to the tissues, and these RBCs are important interorgan communication systems with additional functions, including participation in the control of systemic NO metabolism, redox regulation, blood rheology, and viscosity. RBCs have been shown to induce endothelial dysfunction and increase cardiac injury. The mechanistic links between changes of RBC functional properties and cardiovascular are largely unknown. Extracellular vesicles (EVs) are secreted by most cell types and released in biological fluids both under physiological and pathological conditions. EVs are involved in intercellular communication by transferring complex cargoes including proteins, lipids, and nucleic acids from donor cells to recipient cells. Advancing our knowledge about mechanisms of RBC-EVs formation and their pathophysiological relevance may help to shed light on circulating EVs and to translate their application to clinical practice. We will focus on the potential use of RBC-EVs as valuable diagnostic and prognostic biomarkers and state-specific cargoes, and possibilities as therapeutic vehicles for drug and gene delivery. The use of RBC-EVs as a precision medicine for the diagnosis and treatment of the patient with sleep disorder will improve the prognosis and the quality of life in patients with cardiovascular disease (CVD).