Formation Of Oxygen Free Radicals Research Articles

The potential effect of temulawak (Curcuma xanthorrhiza Roxb.) and garlic (Allium sativum L.) as a radioprotective agent against 6 Gy total body irradiation in rats

The main impact of gamma radiation on a biological system is the formation of Reactive Oxygen Species (ROS) and free radicals. The study aimed to explore the potential effect of temulawak (Curcuma xanthorrhiza Roxb.) and garlic (Allium sativum L.) against 6 Gy total body irradiation (TBI) in rats by observing malondialdehyde (MDA), glutathione (GSH) and comet assay. Twenty male rats were divided into five groups: control, 6 Gy, temulawak extract + 6 Gy, garlic extract + 6 Gy, and n-acetyl cysteine (NAC) + 6 Gy. MDA and GSH were measured on liver and spleen tissue homogenates, while comet assay was on lymphocyte cells. Gamma irradiation at 6 Gy significantly increased the MDA level and comet assay compared to the control group, while the GSH level decreased (p < 0.05). Temulawak extract significantly reduced MDA levels and comet assay compared to the 6 Gy group while increasing GSH levels in the liver. Garlic extract significantly drops comet assay while increasing GSH levels in the liver. NAC decreases MDA levels in the liver and comet assay while increasing GSH levels in the spleen. It could be concluded that temulawak extract has a better radioprotective agent than garlic extract and is almost identical to NAC as a standard antioxidant.

Evaluation of Mitigation Role of L-Phenylalanine-Based Low-Molecular-Weight Gelator against Oil Pollution-Induced Nile Tilapia Toxicity.

A lot of oil is leaked into aquatic environments, significantly impacting fish health and, consequently, human populations. This study aimed to introduce an L-phenylalanine-based low-molecular-weight gelator (expressed as Z-Phe-C18) as a smart remediation tool for oil spills. Several groups of Nile tilapia were allocated in aquaria exposed to different doses of crude engine oil with/without the organogelator for 4 weeks. The results revealed a significant increase in biochemical oxygen demand, chemical oxygen demand, electrical conductivity, and total dissolved solids in water samples of fish aquaria exposed to oil pollution. The antioxidant activity levels, micronucleus formation, and expression patterns of stress-related genes were significantly higher in the livers of fish exposed to crude oil than in those of control fish. On the contrary, fish groups exposed to oil pollution and treated with the organogelator indicated that antioxidant enzymes, micronucleus incidence, and gene expression alteration of stress-related genes declined compared with those exposed to oil pollution only. The results suggest that oil pollution can induce oxidative stress via the enhancement of oxygen free radical formation. On the contrary, oil removal by the organogelator decreases oxidative stress and consequently strengthens fish immunity. So, we can conclude that organogelator treatment is promoting oxidative resistance development by increasing the activities of antioxidant enzymes, which are important in protection against oil pollution and preventing peroxidation of fish tissues. Promisingly, the organogelator could be used as a tool for the remediation of oil pollution in aquatic environments.

Photoenhanced Radical Formation in Aqueous Mixtures of Levoglucosan and Benzoquinone: Implications to Photochemical Aging of Biomass-Burning Organic Aerosols.

The photochemical aging of biomass-burning organic aerosols (BBOAs) by exposure to sunlight changes the chemical composition over its atmospheric lifetime, affecting the toxicological and climate-relevant properties of BBOA particles. This study used electron paramagnetic resonance (EPR) spectroscopy with a spin-trapping agent, 5-tert-butoxycarbonyl-5-methyl-1-pyrroline-N-oxide (BMPO), high-resolution mass spectrometry, and kinetic modeling to study the photosensitized formation of reactive oxygen species (ROS) and free radicals in mixtures of benzoquinone and levoglucosan, known BBOA tracer molecules. EPR analysis of irradiated benzoquinone solutions showed dominant formation of hydroxyl radicals (•OH), which are known products of reaction of triplet-state benzoquinone with water, also yielding semiquinone radicals. In addition, hydrogen radicals (H•) were also observed, which were not detected in previous studies. They were most likely generated by photochemical decomposition of semiquinone radicals. The irradiation of mixtures of benzoquinone and levoglucosan led to substantial formation of carbon- and oxygen-centered organic radicals, which became prominent in mixtures with a higher fraction of levoglucosan. High-resolution mass spectrometry permitted direct observation of BMPO-radical adducts and demonstrated the formation of •OH, semiquinone radicals, and organic radicals derived from oxidation of benzoquinone and levoglucosan. Mass spectrometry also detected superoxide radical adducts (BMPO-OOH) that did not appear in the EPR spectra. Kinetic modeling of the processes in the irradiated mixtures successfully reproduced the time evolution of the observed formation of the BMPO adducts of •OH and H• observed with EPR. The model was then applied to describe photochemical processes that would occur in mixtures of benzoquinone and levoglucosan in the absence of BMPO, predicting the generation of HO2• due to the reaction of H• with dissolved oxygen. These results imply that photoirradiation of aerosols containing photosensitizers induces ROS formation and secondary radical chemistry to drive photochemical aging of BBOA in the atmosphere.

Molecular mechanisms of effects of ionizing radiation action. Irradiation effect on protein (literary review)

Target effects (direct and indirect effects of ionizing radiation). When exposed to ionizing radiation, it damages vital intracellular biomolecules which leads to multiple damage to cells and tissues as well as pathophysiological diseases such as inflammation, immunosuppression, etc. Such damage can be caused by direct ionization of biomolecules, but in almost 70% of cases due to indirect radiolysis of intracellular water with the formation of reactive oxygen species and free radicals, which ultimately causes oxidative stress.Non-target effects (abscopal effect, adaptive response, bystander effect, genomic instability). Over the past 25 years, many studies have explored the molecular mechanisms underlying in nontargeted effects (also known as effects not aimed at DNA). It is shown that these effects are the result of a huge dynamic and complex process induced in irradiated cells, transmitted to neighboring cells and, to some extent, to the whole body through activation of the immune system.The irradiation effect on protein. Under the direct action of ionizing radiation on a protein, an electron is knocked out of it, resulting in a defective site devoid of an electron, which migrates along the polypeptide chain due to the transfer of electrons until it reaches a site with increased electron-donor properties. At this point, free radicals arise in the side chains of amino acids. Under the indirect effect of ionizing radiation, the formation of free radicals occurs when protein molecules interact with the products of water radiolysis.

Effect of silymarin on the parameters of oxidative stress in hearts in the course of diabetes mellitus in Wistar rats

Chronic hyperglycemia is one of the most important causes of the formation of oxygen free radicals in diabetes, which damage various organs. Damage to proteins and lipids in the heart can lead to the development of diabetic cardiomyopathy, which in turn may cause cardiovascular failure. In order to counteract oxidative stress, the innate antioxidant mechanisms of the system should be supported by supplementation with exogenous antioxidants, for instance of plant origin. In this experiment, the role of silymarin, a plant-derived flavonolignan on the oxidative stress parameters and oxidative damage markers in the hearts was determined in an experimental model of diabetes. Male Wistar rats were injected with streptozotocin at a dose of 60 mg/kg (ip). Then, silymarin was administered at doses of 50 and 100 mg/kg for four weeks via a gastric tube. In diabetic animals an increase in malondialdehyde, advanced oxidation protein products, as well as increased activity of antioxidant enzymes in heart tissues was noted. Administration of silymarin inhibited oxidative stress by increasing the total antioxidant response, decreasing the concentration of malondialdehyde and advanced oxidation protein products and a slight increase in the level of glutathione. It can be concluded that the redox state in the examined tissue improved. Based on the results in can be concluded that silymarin demonstrates a potential in preventing the development of oxidative damage in the heart tissue in the course of experimental diabetes.

Preventive Effects of Pimpinella anisum L. and Dracocephalum moldavica L. Hydroalcoholic Extract Against Acute Contrast-induced Nephropathy

Background: Contrast-induced nephropathy (CIN) is nephrotoxicity due to contrast media characterized by elevated serum creatinine levels. The formation of oxygen free radicals is one of the causes of CIN. Objective: Given the antioxidant properties of Pimpinella anisum L and Dracocephalum moldavica L, this study aimed to investigate the effects of their hydroalcoholic extracts on kidney tissue histopathology and CIN biochemical factors. Methods: In this experimental study, 40 male Wistar rats were randomly divided into four groups: 1) control, 2) contrast agent, 3) P. anisum+contrast agent, and 4) D. moldavica+contrast agent. After the tests, kidney tissue histopathological damages and related biochemical factors were evaluated. Results: Kidney tissue damage, levels of aspartate aminotransferase (GOT/AST), alanine aminotransferase (GPT/ALT) and blood urea nitrogen, serum creatinine (P<0.001), and malondialdehyde (P<0.01) of kidney tissue were lower in both extract-treated groups than in contrast agent group, but the decrease in serum MDA was significant only in the group given P. anisum extract (P<0.01). Serum antioxidant capacity was higher in P. anisum+contrast agent group than in the contrast agent group (P<0.01). Kidney tissue antioxidant capacity was significantly higher in the groups given P. anisum and D. moldavica than in the contrast agent group (P<0.01 and P<0.001, respectively). In addition, hydroalcoholic extracts of P. anisum and D. moldavica resulted in a decrease in CIN. Conclusion: Given the decrease in CIN by P. anisum and D. moldavica extracts in rats, it seems that these plants are beneficial for people at risk who need to use contrast agents.

Intermediate products of purine metabolism in an experimental model of pancreatic necrosis.

Determine the level of purines in the blood plasma of experimental animals at three stages of induced pancreatic necrosis. Find out the potential of purines as predictors of the severity of pancreatitis. The experiment was carried out on white outbred rabbits. The pancreatic necrosis was modeled by introducing self-bile into the pancreatic parenchyma. The pancreas of rabbits, after isolation, was subjected to microscopic description. Blood was also taken from rabbits to determine the plasma levels of adenine, guanine, hypoxanthine, xanthine, and uric acid. 12 hours after the administration of self-bile, the level of xanthine significantly increases and the concentration of uric acid in the blood plasma increases by 3 times. 24 hours after the introduction of self-bile, there is a slight decrease in the level of adenine, xanthine and uric acid, and the indicators of purine metabolism remain elevated. 48 hours after the introduction of self-bile, the levels of guanine, hypoxanthine and xanthine are reduced. The concentration indices of absolute and relative intermediate products of purine metabolism were increased at the initial stage of pancreatic necrosis. The activity of enzymes and metabolites of purine metabolism involved in the formation of reactive oxygen species and free radicals increased. The hypothesis that intermediate products of purine metabolism can be predictors of pancreatic necrosis was confirmed.

High Incidence of Clonal Hematopoiesis in Transfusion-Dependent Thalassemia Patients

Introduction: Despite improvement in survival in patients with transfusion-dependent thalassemia (TDT), patients experience significant morbidities, including iron overload, malignancies, thromboembolic events and stroke, and cardiac complications like heart failure and arrhythmias. It is established that global chain imbalance and excess iron leads to significant oxygen stress and to the formation of oxygen free radicals resulting in an increased risk of mutations. Clonal Hematopoiesis of Indeterminate Potential (CHIP) is characterized by the presence of somatic variants in the peripheral blood with a variant allele frequency (VAF) ≥2% in genes associated with hematologic malignancies. These variants occur more frequently with advanced age (~ 10% at age> 65 years). That said, recent data show that young patients with CHIP are at increased risk for developing not only hematological malignancies, but also coronary heart disease, cardiovascular events and stroke. In this study we explored if TDT patients have an increased risk of clonal hematopoiesis and if this observation correlates with their underlying cardiovascular status, thromboembolic complications and history of malignancy. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from ninety five patients with TDT just before their regular transfusion schedule (43 men and 52 women, mean age 39 years old, range 4-55 years ). 40 patients had a history of splenectomy, 32 patients had a history of cardiac disorder (13 patients with atrial fibrillation or other arrhythmias, 19 patients with valvular dysfunction). Genomic DNA was isolated from PBMCs from all patients and Next-Generation Sequencing analysis (NGS) was performed for the mutational status of 58 recurrently mutated genes in myeloid malignancies using a custom-designed Illumina sequencing panel (Illumina, San Diego, CA). Identification of mutations with a VAF ≥2% were reported after bioinformatics analysis and variant interpretation using the Varsome, ClinVar (v.2021) and Franklin databases. Results: Fifteen of 95 patients analyzed (15.8%) displayed mutations in the genes implicated in CHIP. The age-adjusted prevalence of clonal hematopoiesis in patients with TDT vs the reported in the general population is significantly higher. Overall, 22 somatic variants were identified in 15 patients with a median VAF of 40% (range 2.5%-52%): variants were detected in various genes including ATM, FLT3, ASXL1, MPL, SF3B1, BRAF, BTK, TP53, JAK2, RUNX1, ETV6 and EZH2. Four patients carried variants in 4 different genes (TP53, TET2, CEBPA, NPM1) with a mean VAF of 3% (range 2,45% - 4,14%). The patient carrying the TP53 variant is a 44-year old male with a history of splenectomy and arrhythmia (ectopic atrial tachycardia). The patient carrying the TET2 mutation is 55-year old female with a history of colon cancer ten years ago, but no evidence of malignancy relapse as of today. A 5-year old male patient carried a clone in the NPM1 gene with VAF of 2.7%, with no history of splenectomy or cardiac complications. Finally, a 20 year-old male patient carried a clone in the CEBPA gene (VAF 2.7%) along with a clone in the ATM gene (VAF 50.3%). No history of splenectomy, or thromboembolic complications were noted in this patient. Bioinformatics analysis revealed 18 variants in 11 patients with a VAF frequency within the germline range (VAF range 47-52%); germline DNA analysis is ongoing. Seventy TDT patients (73,7%) carried the FLT3 C680T variant that is higher than the incidence reported in gnomAD exome for the European population (60.7%). Ninety three patients carried the ASXL1 T2444C variant, comparable to the observed frequency in the general population. The TET2 C100T variant was observed in 3,1% of the analyzed population compared to the 1.5% reported in the general population. Further analysis revealed that none of the patients had a history of stroke and only two patients had a history of mitral valve regurgitation. Conclusion: We report for the first time that patients with TDT display a significantly higher frequency of variants in genes associated with myeloid malignancies. Life-long stress in the hematopoiesis in these patients may contribute to the increased risk of clonal mutations observed, however further analysis is required to better understand the impact of these observations.

Global warming and glyphosate toxicity (II): Offspring zebrafish modelling with behavioral, morphological and immunohistochemical approaches

The increase in temperature due to global warming greatly affects the toxicity produced by pesticides in the aquatic ecosystem. Studies investigating the effects of such environmental stress factors on next generations are important in terms of the sustainability of ecosystems. In this study, the effects of parental synergistic exposure to glyphosate and temperature increase on the next generation were investigated in a zebrafish model. For this purpose, adult zebrafish were exposed to 1 ppm and 5 ppm glyphosate for 96 h at four different temperatures (28.5, 29.0, 29.5, 30.0 °C). At the end of this period, some of the fish were subjected to the recovery process for 10 days. At the end of both treatments, a new generation was taken from the fish and morphological, physiological, molecular and behavioral analysis were performed on the offspring. According to the results, in parallel with the 0.5-degree temperature increase applied to the parents with glyphosate exposure, lower survival rate, delay in hatching, increased body malformations and lower blood flow and heart rate were detected in the offspring. In addition, according to the results of whole mouth larva staining, increased apoptosis, free oxygen radical formation and lipid accumulation were detected in the offspring. Moreover, it has been observed that the temperature increases to which the parents are exposed affects the light signal transmission and serotonin pathways in the offspring, resulting in more dark/light locomotor activity and increased thigmotaxis.

Antioxidant Properties and Aldehyde Reactivity of PD-L1 Targeted Aryl-Pyrazolone Anticancer Agents.

Small molecules targeting the PD-1/PD-L1 checkpoint are actively searched to complement the anticancer arsenal. Different molecular scaffolds have been reported, including phenyl-pyrazolone derivatives which potently inhibit binding of PD-L1 to PD-1. These molecules are structurally close to antioxidant drug edaravone (EDA) used to treat amyotrophic lateral sclerosis. For this reason, we investigated the capacity of five PD-L1-binding phenyl-pyrazolone compounds (1–5) to scavenge the formation of oxygen free radicals using electron spin resonance spectroscopy with DPPH/DMPO probes. In addition, the reactivity of the compounds toward the oxidized base 5-formyluracil (5fU) was assessed using chromatography coupled to mass spectrometry and photodiode array detectors. The data revealed that the phenyl-pyrazolone derivatives display antioxidant properties and exhibit a variable reactivity toward 5fU. Compound 2 with a N-dichlorophenyl-pyrazolone moiety cumulates the three properties, being a potent PD-L1 binder, a robust antioxidant and an aldehyde-reactive compound. On the opposite, the adamantane derivative 5 is a potent PD-L1 binding with a reduced antioxidant potential and no aldehyde reactivity. The nature of the substituent on the phenyl-pyrazolone core modulates the antioxidant capacity and reactivity toward aromatic aldehydes. The molecular signature of the compound can be adapted at will, to confer additional properties to these PD-L1 binders.

Oxidative Stress, Genomic Integrity, and Liver Diseases

Excess reactive oxygen species production and free radical formation can lead to oxidative stress that can damage cells, tissues, and organs. Cellular oxidative stress is defined as the imbalance between ROS production and antioxidants. This imbalance can lead to malfunction or structure modification of major cellular molecules such as lipids, proteins, and DNAs. During oxidative stress conditions, DNA and protein structure modifications can lead to various diseases. Various antioxidant-specific gene expression and signal transduction pathways are activated during oxidative stress to maintain homeostasis and to protect organs from oxidative injury and damage. The liver is more vulnerable to oxidative conditions than other organs. Antioxidants, antioxidant-specific enzymes, and the regulation of the antioxidant responsive element (ARE) genes can act against chronic oxidative stress in the liver. ARE-mediated genes can act as the target site for averting/preventing liver diseases caused by oxidative stress. Identification of these ARE genes as markers will enable the early detection of liver diseases caused by oxidative conditions and help develop new therapeutic interventions. This literature review is focused on antioxidant-specific gene expression upon oxidative stress, the factors responsible for hepatic oxidative stress, liver response to redox signaling, oxidative stress and redox signaling in various liver diseases, and future aspects.

Black Bean (Phaseolus vulgaris L.) Polyphenolic Extract Exerts Antioxidant and Antiaging Potential.

Phenolic compounds present in common beans (Phaseolus vulgaris L.) have been reported to possess antimicrobial, anti-inflammatory and ultraviolet radiation (UVR) protective properties. UVR from sunlight, which consists of UV-B and UV-A radiations, induces reactive oxygen species (ROS) and free radical formation, consequently activating proteinases and enzymes such as elastase and tyrosinase, leading to premature skin aging. The objective of this work was to extract, characterize and evaluate the antioxidant and antiaging potential of polyphenols from a black bean endemic variety. The polyphenolic extract was obtained from black beans by supercritical fluid extraction (SFE) using CO2 with a mixture of water–ethanol as a cosolvent and conventional leaching with a mixture of water–ethanol as solvent. The polyphenolic extracts were purified and characterized, and antioxidant potential, tyrosinase and elastase inhibitory potentials were measured. The extract obtained using the SFE method using CO2 and H2O–Ethanol (50:50 v/v) as a cosolvent showed the highest total phenolic compounds yield, with 66.60 ± 7.41 mg GAE/g coat (p > 0.05) and 7.30 ± 0.64 mg C3GE/g coat (p < 0.05) of anthocyanins compared to conventional leaching. Nineteen tentative phenolic compounds were identified in leaching crude extract using ESI-QTOF. Quercetin-3-D-galactoside was identified in crude and purified extracts. The purified SFC extract showed IC50 0.05 ± 0.002 and IC50 0.21 ± 0.008 mg/mL for DPPH and ABTS, respectively. The lowest IC50 value of tyrosinase inhibition was 0.143 ± 0.02 mg/mL and 0.005 ± 0.003 mg/mL of elastase inhibition for leaching purified extract. Phenolic compounds presented theoretical free energy values ranging from −5.3 to −7.8 kcal/mol for tyrosinase and −2.5 to −6.8 kcal/mol for elastase in molecular docking (in silico) studies. The results suggest that the purified extracts obtained by SFE or conventional leaching extraction could act as antioxidant and antiaging ingredients for cosmeceutical applications.

8‐oxoguanine glycosylase (OGG1) is a determinant of endothelial dysfunction via calcium and nitric oxide signaling

Diabetes mellitus is a chronic disease that hinders the body's ability to produce or respond to the hormone insulin, resulting in abnormal metabolism and elevated glucose levels. Type II diabetes has been characterized by a two-to-four-fold increase in cardiovascular disease, such as carotid artery stenosis, generally attributed to the adverse effects of hyperglycemia and oxidative stress on vascular biology. With it being a very common and significant health complication, understanding the pathology and the mechanisms by which diabetes-induced oxidative stress serves as a precursor to several notable vascular diseases is paramount, and is the overall objective of this study. Endothelial dysfunction (ED) is a vascular phenomenon attributed to a reduction in nitric oxide (NO) bioactivity and an increase in oxygen free radical formation with subsequent oxidative stress, thus leading to impaired vasodilation, and compromised vascular function. ED tends to be a consistent finding in diabetes. A major source of oxidative stress is the abnormal production of reactive oxygen species (ROS) in the context of diabetic inflammation. Increased ROS production leads to mitochondrial DNA (mt DNA) damage and aberrant cell signaling. Typically, mt DNA damage is repaired through the base excision repair (BER) pathway. However, during chronic inflammation in diabetes, this repairing capability is ineffective due to downregulation of key BER enzymes, namely 8-oxoguanine glycosylase (OGG1). Given this rational, we hypothesized that the BER pathway is an important determinant of endothelial dysfunction via impaired calcium and NO signaling. To test this hypothesis, we examined the effect of BER defects on endothelial calcium signaling and NO production using carotid arteries isolated from mice deficient in OGG1. Opened artery measurements of endothelial calcium and NO signaling were performed using a custom-designed parallel plate flow chamber. Briefly, segments of carotid arteries (~200 µm in diameter) were isolated from OGG1 deficient (KO) and wild type (WT) mice and cut open lengthwise to expose the endothelial surface. The isolated vessels were then stained with a loading solution composed of Pluronic acid (Fischer), Cal-520 (AAT bio) calcium indicator dye and DAR-4M (Calbiochem), a fluorescent probe for NO. Time lapse signal measurements were collected via confocal microscopy and were then analyzed and processed with S8, a custom automated solution to signal analysis based on noise filtering and object tracking, which computed dynamic amplitude, frequency, duration, and spatial spread. We discovered that although the number of calcium signals detected within the measurement interval were similar between KO and WT (10 ± 3 vs 9 ± 3, µ ± SEM, respectively), the spatial spread of signals within the KO (19.95 ± 3.78 µm2, µ ± SEM) was greater than WT (9.65 ± 2.7 µm2, p = 0.057 via Welch's unpaired t-test). These data suggest that OGG1 may be a determinant of normal endothelial calcium signaling and might serve as a therapeutic target for preventing the adverse effects of endothelial dysfunction present in diabetes.

Toxin-Antitoxin Systems - A New Player in Morphological Transformation of Antibiotic-Exposed Helicobacter pylori?

Toxin-Antitoxin Systems - A New Player in Morphological Transformation of Antibiotic-Exposed Helicobacter pylori?

Biological effects of oxygen-enriched drinking water. Review. Part 2

Human life on Earth depends on the continuous availability of oxygen. Conditions for the entry of oxygen into the body’s cells change in time and space, are easily broken, thus causing the possibility of development of hypoxia - a condition of oxygen starvation of tissues. The second part of the review is devoted to information about the successful use of oxygen-rich water in domestic therapeutic and surgical practice in complex treatment to reduce the negative effect of hypoxia in patients with chronic heart failure and generalized peritonitis complicated by intestinal insufficiency syndrome. Authors consider a common method for improving the supply of oxygen to the body using enteral oxygen therapy - oxygen cocktails in diseases of the cardiovascular system, lungs, bronchi and gastrointestinal tract, atopic dermatitis, placental insufficiency, as well as to improve physical performance, reduce the level of neuroticism and normalize the psychoemotional status. The first part of the review provides data on the modern understanding processes providing oxygen homeostasis in cells, on the critical component responsible for regulating the molecular response to hypoxia - the Hypoxia-Inducible Factors (HIFs) of the family of transcription factors. The possibility to compensate for the lack of oxygen in the body by delivering it to cells and tissues was indicated to consider water and various oxygen cocktails. Data from experimental studies of the biological effect of oxygenated drinking water are analyzed, as well as the results of studying the effects of oxygen-enriched drinking water with the participation of volunteers. The issue of the formation of oxygen (free) radicals when drinking oxygen-enriched drinking water is considered. The review draws specialist’s attention to the problem of the biological effect of oxygen-enriched drinking water, its insufficient knowledge and the possible yet unrealized potential in terms of preventing various diseases and maintaining optimal human health.

Biological effects of oxygen-enriched drinking water. Review. Part 1

Human life on Earth depends on the continuous availability of oxygen, but conditions for the entry of oxygen into the cells of the body change in time and space, easily broken, owing to what may develop hypoxia - a condition of oxygen starvation of tissues. The first part of the review provides information on the maintenance of oxygen homeostasis in cells, on the key component responsible for the regulation of the molecular response to hypoxia - the HIFs family of transcription factors (Hypoxia-Inducible Factors). It is indicated that it is possible to compensate for the lack of oxygen in the body by delivering it to cells and tissues with water and various oxygen cocktails. Data from experimental studies of the biological effect of oxygenated drinking water, as well as the results of studying the effects of oxygen-enriched drinking water with the participation of volunteers are presented. The issue of the formation of oxygen (free) radicals when drinking oxygen-enriched drinking water is considered. The second part of the review will provide data on the successful use of oxygen-rich water in domestic therapeutic and surgical practice in complex treatment in order to reduce the negative effect of hypoxia in patients with chronic heart failure and generalized peritonitis complicated by intestinal insufficiency syndrome; on the method of improving the supply of oxygen to the body using enteral oxygen therapy - oxygen cocktails - for diseases of the heart, lungs, bronchi and gastrointestinal tract, atopic dermatitis, placental insufficiency, as well as to improve physical and mental performance. The review draws specialist’s attention to the problem of the biological effect of oxygen-enriched drinking water, its insufficient knowledge and the possible yet unrealized potential in terms of preventing various diseases and maintaining optimal human health.

Dietary Thiols: A Potential Supporting Strategy against Oxidative Stress in Heart Failure and Muscular Damage during Sports Activity.

Moderate exercise combined with proper nutrition are considered protective factors against cardiovascular disease and musculoskeletal disorders. However, physical activity is known not only to have positive effects. In fact, the achievement of a good performance requires a very high oxygen consumption, which leads to the formation of oxygen free radicals, responsible for premature cell aging and diseases such as heart failure and muscle injury. In this scenario, a primary role is played by antioxidants, in particular by natural antioxidants that can be taken through the diet. Natural antioxidants are molecules capable of counteracting oxygen free radicals without causing cellular cytotoxicity. In recent years, therefore, research has conducted numerous studies on the identification of natural micronutrients, in order to prevent or mitigate oxidative stress induced by physical activity by helping to support conventional drug therapies against heart failure and muscle damage. The aim of this review is to have an overview of how controlled physical activity and a diet rich in antioxidants can represent a “natural cure” to prevent imbalances caused by free oxygen radicals in diseases such as heart failure and muscle damage. In particular, we will focus on sulfur-containing compounds that have the ability to protect the body from oxidative stress. We will mainly focus on six natural antioxidants: glutathione, taurine, lipoic acid, sulforaphane, garlic and methylsulfonylmethane.

Оксидативный стресс у животных: роль в онкогенезе глазами патоморфолога

Oxidative stress is a pathological accumulation of free radicals that contribute to the launch of intracellular damaging action mechanisms. Free radical is an atom possessing free or missing electron, and seeking to restore the lost electron, taking it from other molecules ― as a result a new free radical is formed. The mechanism is chain reaction-based. Hypoxia acts as an additional stimulus to the appearance of oxygen free radicals. Cell hypoxia develops following any type of cell damage: mechanical, bacteriological, chemical, etc. Cell hypoxia inevitably leads to the development of an inflammatory reaction, which is followed by the formation of oxygen free radicals and, as a result, by oxidative stress development.

Biochemistry of mammalian ferritins in the regulation of cellular iron homeostasis and oxidative responses.

Ferritin, an iron-storage protein, regulates cellular iron metabolism and oxidative stress. The ferritin structure is characterized as a spherical cage, inside which large amounts of iron are deposited in a safe, compact and bioavailable form. All ferritins readily catalyze Fe(II) oxidation by peroxides at the ferroxidase center to prevent free Fe(II) from participating in oxygen free radical formation via Fenton chemistry. Thus, ferritin is generally recognized as a cytoprotective stratagem against intracellular oxidative damage The expression of cytosolic ferritins is usually regulated by iron status and oxidative stress at both the transcriptional and post-transcriptional levels. The mechanism of ferritin-mediated iron recycling is far from clarified, though nuclear receptor co-activator 4 (NCOA4) was recently identified as a cargo receptor for ferritin-based lysosomal degradation. Cytosolic ferritins are heteropolymers assembled by H- and L-chains in different proportions. The mitochondrial ferritins are homopolymers and distributed in restricted tissues. They play protective roles in mitochondria where heme- and Fe/S-enzymes are synthesized and high levels of ROS are produced. Genetic ferritin disorders are mainly related to the L-chain mutations, which generally cause severe movement diseases. This review is focused on the biochemistry and function of mammalian intracellular ferritin as the major iron-storage and anti-oxidation protein.

THE IMPACT OF OXYGEN FREE RADICAL SCAVENGER ON ACUTE REJECTION IN A HISTOCOMPATIBLE MINIATURE SWINE MODEL

Introduction: Vascularized Composite Allotransplantations (VCAs), like solid organ transplants, are very susceptible to ischemia-reperfusion injury (IRI). IRI leads to tissue hypoxia and the formation of oxygen free radicals which triggers T-cell accumulation and complement activation, causing increased antigenicity of the transplanted tissue. In this study we demonstrate the effect of two oxygen free radical scavengers on acute rejection in a histocompatible miniature swine model. Materials and Methods: To conduct this study, we used our well-established myocutaneous flap model in a major histocompatibility complex (MHC)-defined miniature swine. MHC class I and II antigens were matched between donors and recipients. Myocutaneous allografts consisted of an isolated skin pad with the underlying gracilis muscle. All flaps were treated with similar concentrations of either Saline (9mg/ml, n=2), Sodium Iodide (10mg/ml, n=3) or Hydrogen Sulfide (H2S) (11.6mg/ml). Flaps were subjected to an intermediate ischemia time of 3 hours at 4°C immediately after harvest. End of ischemia time was marked by unclamping the anastomosis. Daily blood draws were performed on postoperative day (POD) 0 to 7, 14 and end of study. Biopsies for histological analysis were collected on POD 4, 10, 14 and end of study. Rejection was assessed by an independent pathologist following the Banff criteria (Grade 0-IV) for skin containing VCA. Results: On POD 4, flaps treated with H2S showed Grade 0 of rejection according to the Banff classification, compared to Grade I in the Sodium Iodide group and Grade II in the Saline. There was no significant difference in grade of rejection between these three groups on or after POD 10.Discussion: Treatment of ischemic myocutaneous flaps with oxygen free radical scavengers delayed acute rejection when compared to saline treated controls. Currently, standard immunosuppression regimens and techniques for graft preservation of VCA do not enable preconditioning of the donor or ischemic-free storage. Therefore, IRI is unavoidable in VCA so far. Diminishing the impact of IRI could reduce local secretion of pro-inflammatory cytokines and sequester recruitment of alloreactive immune cells to the transplant, delaying acute rejection episodes during the immediate post-operative period. Conclusion: With this study we demonstrate the impact of oxygen free radical scavengers on IRI in an immunocompetent and genetically well-defined large animal model. Treating myocutaneous flaps accordingly abrogates early rejection histopathologically at POD 4. Further experiments are ongoing to titrate the impact of these scavengers across later timepoints.