Intensity Of Oxidative Stress Research Articles

Selected Atherosclerosis-Related Diseases May Differentially Affect the Relationship between Plasma Advanced Glycation End Products, Receptor sRAGE, and Uric Acid.

Our study aimed to identify the relationship between advanced glycation end products (AGEs), soluble receptor for advanced glycation end products (sRAGE), the AGEs/sRAGE, and uric acid (UA) levels in selected atherosclerosis diseases, i.e., abdominal aortic aneurysms (AAA), aortoiliac occlusive disease (AIOD), and chronic kidney disease (CKD), resulting from apparent differences in oxidative stress intensity. Furthermore, we suggest that increased AGEs levels may stimulate an antioxidant defense system reflected by the UA level. The studied group size consisted of 70 AAA patients, 20 AIOD patients, 50 patients in the pre-dialyzed group (PRE), and 35 patients in the hemodialyzed group (HD). The enzyme-linked immunosorbent assay was used to measure AGEs and sRAGE levels. We found a significantly higher concentration of AGEs in CKD patients as compared to AAA and AIOD patients. Furthermore, the sRAGE level was higher in the CKD patients in comparison to AIOD and AAA patients. UA level was significantly higher in the PRE group compared to AAA patients. In conclusion, the diseases included in this study differ in the anti- and prooxidant defense system, which is reflected in the relations between the AGEs, the sRAGE, the AGEs/sRAGE ratio, as well as the UA levels.

Indicator Characterizing Carbonyl-Dependent Modification of Erythrocytic Superoxydismutase as a Biochemical Marker of Oxidative Stress in Coronary Heart Disease

Aim To study the oxidative modification of red blood cell Cu,Zn superoxide dismutase (SOD) in patients with ischemic heart disease (IHD) in vivo and in vitro to substantiate the use of a new oxidative stress marker.Material and methods Red blood cell Cu,Zn SOD was measured by depression of nitrotetrazolium blue reduction by the superoxide anion generated in xanthine oxidase xanthine oxidation. Red blood cell Cu,Zn SOD was measured immunochemically. The biochemical study was performed in the control group (patients with low extremity fracture without known history of cardiovascular diseases and hyperlipidemia) and in groups of patients with acute myocardial infarction, stable angina, and decompensated heart failure. For evaluation of oxidative stress intensity in IHD patients, an empirical SOD oxidative modification coefficient (OMCSOD) was proposed, which is a Cu,Zn SOD activity / Cu,Zn SOD content ratio.Results The red blood cell Cu,Zn SOD activity was significantly decreased in all IHD groups compared to the control group. Furthermore, OMCSOD was also considerably decreased in IHD patients, which warrants the use of this biochemical index as an oxidative stress marker.Conclusion It was shown that the Cu,Zn SOD modification was induced by interaction of the enzyme molecules with a natural dicarbonyl, malonic dialdehyde, and OMCSOD can be used for evaluation of oxidative stress intensity in IHD patients.

Мелатонин и его роль в регуляции устойчивости сердца к действию ишемии и реперфузии

Цель обзора - анализ публикаций, посвященных кардиопротекторным эффектам мелатонина в условиях ишемии/реперфузии сердца в эксперименте и клинике. Эксперименты в анализируемых статьях проводились на крысах с коронароокклюзией и реперфузией. Некоторые исследования выполнялись на изолированном перфузируемом сердце крысы, которое подвергали ишемии/реперфузии. Для блокады рецепторов мелатонина использовался Лузиндол. Клинические исследования проводились на пациентах с острым инфарктом миокарда с подъёмом сегмента ST и чрескожным коронарным вмешательством. Мелатонин вводился внутривенно. Размер инфаркта оценивался по уровню креатинкиназы-МВ, тропонина Т и с помощью магнитно-резонансной томографии. Кроме того, клинические исследования выполнялись на пациентах с коронарным шунтированием. В экспериментальных работах доказывается, что мелатонин повышает толерантность сердца к ишемии/реперфузии: способствует уменьшению соотношения зона инфаркта/область риска, оказывает антиапоптотический эффект, улучшает насосную функцию сердца во время реперфузии, обеспечивает антиаритмический эффект, снижает интенсивность окислительного стресса. Многие из этих эффектов связаны с активацией М1- и М2-рецепторов. В клинических исследованиях обосновывается, кардиопротекторное действие мелатонина у пациентов с коронарным шунтированием. Данные об эффективности мелатонина у пациентов с острым инфарктом миокарда противоречивы. Заключение. Вопрос о клинической эффективности мелатонина требует дальнейшего изучения.The aim was to analyze publications addressing the cardioprotective effects of melatonin in ischemia/reperfusion of the heart. Experiments in the analyzed reports were performed on rats with coronary artery occlusion and reperfusion. Some studies were performed on isolated, perfused rat hearts subjected to ischemia/reperfusion. Luzindole was used to antagonize melatonin receptors. Clinical studies were conducted on patients with acute ST-segment elevation myocardial infarction who underwent a percutaneous coronary intervention. Melatonin was administered intravenously. Infarct size was estimated by concentrations of creatine kinase-MB and troponin T and also using magnetic resonance imaging. In addition, clinical studies were performed on patients with coronary artery bypass surgery. Melatonin increased the heart tolerance to ischemia/reperfusion by providing a decrease in the infarct size/area at risk ratio; exerting an antiapoptotic effect; improving the heart pumping function during reperfusion; exerting an antiarrhythmic effect; and reducing the intensity of oxidative stress. Many of these effects were associated with activation of M1 and M2 receptors. Melatonin proved cardioprotective in patients with coronary artery bypass grafting. Data on the effectiveness of melatonin in patients with acute myocardial infarction are inconsistent. Conclusion The question of the clinical efficacy of melatonin requires further study.

Free Radical Oxidation and Sleep Disorders in Andro- and Menopause (Literature Review)

This review presents data on changes in the physiology of sleep during reproductive aging. It is noted that insomnia and obstructive sleep apnea syndrome (OSAS) are the main sleep disorders. The results of foreign and domestic studies in the field of free radical oxidation during sleep deprivation in animal models are presented, indicating the dependence of processes on the duration of sleep deprivation. The largest number of studies of free radical processes in a person with somnological pathology was carried out in the study of OSAS. Blood, urine, saliva, condensate of exhaled air can be biomaterial for determining the parameters of free radical oxidation. It was shown that the intensity of oxidative stress depends on the severity of OSAS, as evidenced by the positive correlation of the level of active products of thiobarbituric acid, the products of oxidation of proteins and carbonyl groups with the apnea/hypopnea index, determining the development of not only oxidative, but also carbonyl stress in patients with a severe degree OSAS. Biomarkers such as thioredoxin, malondialdehyde, superoxide dismutase, and reduced iron have shown a more stable relationship between increased oxidative stress and OSA. Despite the results obtained, the question of the association of oxidative stress and hypoxia in OSA remains debatable, which is associated with the opposite results of some studies. Insomnia, which occurs mainly in females, is accompanied by a high level of end products of lipid peroxidation with a decrease in the activity of antioxidants such as paraoxonase, an enzymatic component of the glutathione system. Along with this, menopausal women present low levels of uric acid, which correlates with high scores of the Pittsburgh sleep quality index questionnaire. Recent studies have identified an association between the activity of the «lipoperoxidation – antioxidants» system and the Clock 3111T/C gene polymorphism in menopausal Caucasian women, indicating the protective role of the minor allele.

Influence of Bone Marrow-Derived Mesenchymal Stem Cell Therapy on Oxidative Stress Intensity in Minimally Conscious State Patients.

Neurological disorders, including minimally conscious state (MCS), may be associated with the presence of high concentrations of reactive oxygen species within the central nervous system. Regarding the documented role of mesenchymal stem cells (MSCs) in oxidative stress neutralization, the aim of this study is to evaluate the effect of bone marrow-derived MSC (BM-MSC) transplantation on selected markers of oxidative stress in MCS patients. Antioxidant capacity was measured in cerebrospinal fluid (CSF) and plasma collected from nine patients aged between 19 and 45 years, remaining in MCS for 3 to 14 months. Total antioxidant capacity, ascorbic acid and ascorbate concentrations, superoxide dismutase, catalase, and peroxidase activity were analyzed and the presence of tested antioxidants in the CSF and plasma was confirmed. Higher ascorbic acid (AA) content and catalase (CAT) activity were noted in CSF relative to plasma, whereas superoxide dismutase (SOD) activity and total antioxidant capacity were higher in plasma relative to CSF. Total antioxidant capacity measured in CSF was greater after BM-MSC transplantations. The content of ascorbates was lower and CAT activity was higher both in CSF and plasma after the administration of BM-MSC. The above results suggest that MSCs modulate oxidative stress intensity in MCS patients, mainly via ascorbates and CAT activity.

OXIDATIVE STRESS INTENSITY AND STATE OF SEPARATE ANTIOXIDANT PROTECTION FACTORS IN ANTRALE TREATMENT IN PATIENTS WITH NONALCOHOLIC STEATOHEPATITIS, OBESITY, AND CHRONIC OBSTRUCTIVE LUNG DISEASE

The aim of the research was to assess the effectiveness of Antral regarding the impact on the intensity of lipid peroxidation, antioxidant system factors in NASH patients against the background of obesity and comorbidity with COPD. Material and methods of research: 76 NASH patients with class I obesity of and COPD 2-3 D were examined: 23 patients (group 1 – control group) received basic NASH therapy (Esentsiale forte N (Sanofi Avensis/Gutterman and Cie GmbH) 300 mg, 2 caps., 3 times per day) for 30 days and COPD therapy (Symbicort Turbuhaler (budesonide 160 mg/d + formoterol fumarate 4,5 mg/s) (AstraZeneca AB, Sweden) inhaled 2 times per day for 30 days, Berodual (ipratropium/fenoterol (250/500 mg/ml) (Institute de Angele Italy/Boehringer Ingelheim International GmbH) nebulizer inhalation 2 times per day, azithromycin (Azithro Sandoz, Ukraine Sandoz) 500 mg, 1 time per day for 10 days). The second group (basic group, B1) consisted of 25 NASH patients with class I obesity and COPD 2-3 D, in addition to the same basic COPD therapy, they received Antral (Farmak, Ukraine) 200 mg, 3 times per day for 60 days as a hepatoprotection. The third group (basic group, B2) included 28 NASH patients with class I obesity and COPD 2-3 D, except the same basic COPD treatment, they received Antral (Farmak, Ukraine) 200 mg, 3 times per day as a hepatoprotection, and Phytostatin (Polyconazole) (OmniFarma LLC, Ukraine) 20 mg after dinner for 30 days. Research results. In NASH patients against the background of obesity and COPD, a significant intensity of oxidative stress has been established with an increase in the blood of intermediate and final products of lipid peroxidation content (in 1.7–2.2 times, p < 0.05) against the background of a significant deficit in the restored glutathione in the blood (in 1.6 times, p < 0.05), which was accompanied by a compensatory voltage of catalase activity (increases in 1.7 times, p < 0.05). Conclusion. The combined prescription of Antral for 30 days led to a significant correction of oxidative-antioxidant homeostasis in NASH patients against the background of obesity and COPD with a probable decrease of malonic aldehyde, isolated double bonds, conjugated dienes (p < 0.05), a probable increase the reduced glutathione content in red blood cells (p < 0.05).

Investigation of the thiol-disulfide system state of rats with encephalopathy caused by the effect of antituberculous drugs

Objective. To determine in an experimental study the nature of changes in the status of the thiol-disulfide system of rats with encephalopathy, due to the influence of complex of anti-tuberculosis drugs for the treatment of chemoresistant tuberculosis and the possibility of their drug correction with the use of ademetionine 1,4-butanedisulfonate.Materials and methods. The study was conducted on 30 Wistar rats, which were divided into 3 groups: 10 – intact group, 10 – control group (treated with antituberculosis drugs) and 10 – main group (treated with antituberculosis drugs and ademetionine as means of correcting toxic effects). The state of the glutathione system and the content of homocysteine and nitrotyrosine were investigated.Results. Experimental therapy with ademetionine in rats treated with antituberculosis drugs helps to reduce the intensity of chronic oxidative stress in nerve tissue. The introduction of ademetionine establishes the most optimal ratio between the levels of reduced and oxidized thiol groups, as well as glutathione, which indicates the active mobilization of the thiol-disulfide system and the neutralization of products of free-radical oxidation. Under the conditions of nitrosative and oxidative stress, the studied agents increase the resistance of nervous tissue to the manifestations of intoxication. Thus, one of the links of the neuroprotective effect of ademetionin was its ability to stabilize the thiol-disulfide equilibrium.Conclusions. In the functioning of the glutathione-dependent enzymatic system in the tissues of the brain of rats treated with anti-tuberculosis drugs, there was decreased activity of glutathione s-transferase, glutathione peroxidase and glutathione reductase by 2.0, 1.7 and 2.4 times, respectively. Under the conditions of ademetionin therapy, there was increase by 1.7 times in the reduced intermediates of the thiol-disulfide system – SH-group, and an increase of the level of reduced glutathione by 1.9 times, against the background of a significant decrease in the content of its oxidized form – 1.4 times. The use of ademetionin also led to a decrease of the content of potentially neurotoxic compounds - nitrotyrosine and homocysteine by 1.4 and 1.5 times, respectively in the brain tissues, which increases the resistance of nervous tissue to the effects of intoxication.

Sitagliptin-Dependent Differences in the Intensity of Oxidative Stress in Rat Livers Subjected to Ischemia and Reperfusion.

Purpose Ischemia/reperfusion (IR) is the main cause of liver damage after transplantation. We evaluated the effect of sitagliptin (STG) on oxidative stress parameters in the rat liver under IR. Methods Rats were treated with STG (5 mg/kg) (S and SIR) or saline solution (C and CIR). Livers from CIR and SIR were subjected to ischemia (60 min) and reperfusion (24 h). During reperfusion, aminotransferases (ALT and AST) were determined in blood samples. Thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), paraoxonase-1 (PON1), glutathione peroxidase (GPx), and the mRNA expression of SOD1 were determined in liver homogenates after reperfusion. Different regions of livers were also histologically evaluated. Results The PON1 activity was higher, and the TBARS level was lower in SIR than in CIR. There was an inverse relationship between TBARS and PON1 levels in the whole cohort. The GPx activity was lower in ischemic than in nonischemic groups regardless of the STG treatment. In SIR, the SOD1 activity was higher compared to that in CIR. In S, the expression of SOD1 mRNA was the highest of all examined groups and positively correlated with the SOD1 activity in the whole animal cohort. During IR aminotransferases, the activity in the drug-treated group was lower in all examined points of time. In drug-treated groups, the percentage of steatosis was higher than that in nontreated groups regardless of IR. Conclusions The protective effect of STG on the rat liver, especially its antioxidant properties, was revealed under IR conditions.

Effect of Tripeptide Leu-Ile-Lys on the Course of Experimental Nephrolithiasis.

We studied the effect of Leu-Ile-Lys tripeptide on the course of experimental oxalate nephrolithiasis modeled in rats by administration of 1% ethylene glycol solution instead of drinking water for 6 weeks. The Leu-Ile-Lys tripeptide obtained by chemical synthesis (purity ≥98%) was administered through a gastric tube (11.5 mg/kg in 1 ml saline). Administration of Leu-Ile-Lys tripeptide against the background of experimental oxalate nephrolithiasis significantly alleviated the course of experimental pathology, which was confirmed by typical biochemical and morphological changes: decrease in urinary activity of γ-glutamyltransferase (by 2.1 times in comparison with the initial level) and intensity of oxidative stress (the content of TBA-reactive products decreased by 1.3 times in comparison with that in untreated animals) and increase in glutathione peroxidase activity by 1.8 times; no histological signs of nephrolithiasis were found in animals treated with the tripeptide.

Effect of Primary and Secondary Beads of Carbon Enterosorbent on Haematological Parameters and Oxidative Stress Development Caused by Melphalan in Rats.

Background and Objectives: Side effects of anti-cancer drugs are usually accompanied by oxidative stress, including myelotoxicity. We evaluated the potential of oral highly activated micro-/macroporous carbon adsorbents (bulk density of 0.16 g/cm3, surface area calculation by Brunauer–Emmett–Teller model (SBET) > 2200 m2/g, derived from proprietary phenolic resin beads) to alleviate oxidative stress and myelotoxicity in rats. Materials and Methods: A single injection of cytostatic melphalan (L-PAM) at a dose of 4 mg/kg was used for modelling. Two forms of activated carbon were used: AC1—primary beads with the particle size range of 125–250 µm, and AC2—micronized AC1 with a mean particle size of ~1 µm. We measured haematological parameters white blood cells, red blood cells, platelet count, and haemoglobin level. Oxidative stress intensity was evaluated using the following markers: total levels of reactive oxygen species (ROS) in blood plasma; catalase activity (CAT) and pro-oxidant/antioxidant ratio in blood haemolysate samples; level of reduced glutathione (GSH) in liver tissues; oxidative modification of proteins, OPM (APHD, aldehyde–dinitrophenylhydrazone derivatives and KPHD, ketone dinitrophenylhydrazone derivatives) and malonic dialdehyde (MDA) in blood plasma and liver samples. Results: AC2 administration promoted significant myeloprotective effect: 1.5-fold increase in leukocytes, 2-fold in neutrophils, 1.5-fold in lymphocytes, and 1.23-fold in platelet count compared to the experimental Melphalan Group. At the same time, AC1 administration resulted in a slight increase in haematological parameters. Both ACs positively corrected important, but diverse, components of oxidative stress. They significantly reduced oxidative modification of blood and liver proteins (especially the AC1 form), normalized the level of reduced glutathione, pro-oxidant/antioxidant ratio and other markers. For some markers, such as ROS production in blood plasma, the use of enterosorbents resulted in non-significant a shift towards normal parameters. Conclusions: Oral activated carbon adsorbents reduce oxidative stress intensity and myelotoxicity; they can be promising means to combat the adverse effects of chemotherapy in clinical practice.

Rapid or Slow Time to Brain Death? Impact on Kidney Graft Injuries in an Allotransplantation Porcine Model.

The use of donors deceased after brain death (DBD) with extended criteria in response to the shortage of grafts leads to the removal of more fragile kidneys. These grafts are at greater risk of not being grafted or delayed function. A better knowledge of the pathophysiology of DBDs would improve this situation. There is a difference between the results from animal models of DBD and the clinical data potentially explained by the kinetics of brain death induction. We compared the effect of the induction rate of brain death on the recovery of post-transplant renal function in a pig model of DBD followed by allografts in nephrectomized pigs. Resumption of early function post-transplant was better in the rapidly generated brain death group (RgBD) and graft fibrosis at three months less important. Two groups had identical oxidative stress intensity but a greater response to this oxidative stress by SIRT1, PGC1-α and NRF2 in the RgBD group. Modulation of mechanistic target of rapamycin (mTOR) stimulation by NRF2 would also regulate the survival/apoptosis balance of renal cells. For the first time we have shown that an allostatic response to oxidative stress can explain the impact of the rapidity of brain death induction on the quality of kidney transplants.

Oxidative stress links response to lead and Acyrthosiphon pisum in Pisum sativum L.

This study demonstrates the impact of lead at hormetic (0.075 mM Pb(NO3)2) and sublethal (0.5 mM Pb(NO3)2) doses on the intensity of oxidative stress in pea seedlings (Pisum sativum L. cv. ‘Cysterski’). Our first objective was to determine how exposure of pea seedlings to Pb alters the plant defence responses to pea aphid (Acyrthosiphon pisum Harris), and whether these responses could indirectly affect A. pisum. The second objective was to investigate the effects of various Pb concentrations in the medium on demographic parameters of pea aphid population and the process of its feeding on edible pea. We found that the dose of Pb sublethal for pea seedlings strongly reduced net reproductive rate and limited the number of A. pisum individuals reaching the phloem. An important defence line of pea seedlings growing on Pb-supplemented medium and next during combinatory effect of the two stressors Pb and A. pisum was a high generation of superoxide anion (O2−). This was accompanied by a considerable reduction in superoxide dismutase (SOD) activity, and a decrease in the level of Mn2+ ions. A the same time, weak activity of Mn-SOD was detected in the roots of the seedlings exposed to the sublethal dose of Pb and during Pb and aphid interaction. Apart from the marked increase in O2−, an increase in semiquinone radicals occurred, especially in the roots of the seedlings treated with the sublethal dose of Pb and both infested and non-infested with aphids. Also, hydrogen peroxide (H2O2) generation markedly intensified in aphid-infested leaves. It reached the highest level 24 h post infestation (hpi), mainly in the cell wall of leaf epidermis. This may be related to the function of H2O2 as a signalling molecule that triggers defence mechanisms. The activity of peroxidase (POX), an important enzyme involved in scavenging H2O2, was also high at 24 hpi and at subsequent time points. Moreover, the contents of thiobarbituric acid reactive substances (TBARS), products of lipid peroxidation, rose but to a small degree thanks to an efficient antioxidant system. Total antioxidant capacity (TAC) dependent on the pool of fast antioxidants, both in infested and non-infested and leaves was higher than in the control. In conclusion, the reaction of pea seedlings to low and sublethal doses of Pb and then A. pisum infestation differed substantially and depended on a direct contact of the stress factor with the organ (Pb with roots and A. pisum with leaves). The probing behavior of A. pisum also depended on Pb concentration in the plant tissues.

Dose dependent acute toxicity of abrin in Balb/c mice after intraperitoneal administration

Abrin toxin is one of the most potent and deadly plant toxin obtained from the seeds of Abrus precatorious. It is more toxic than ricin which is classified as Schedule 1 agent by OPCW and Category B bioterrorism agent by Centre for Disease Control (CDC). Dose dependent acute toxicity of abrin is still a matter of investigation. The present study was carried out to assess the toxicity of abrin from sub lethal to supralethal doses (0.5X, 1X, 2X and 5XLD50) after intraperitoneal administration. After 8 and 24h of abrin exposure, hematological, biochemical, inflammatory and oxidative stress associated parameters were analyzed. Liver histology was also done to analyze the effect of abrin. Abrin exerts its toxicity in a dose and time dependent manner. Increases in neutrophil counts, lipid peroxidation with decreased lymphocyte counts, are the initiating factor irrespective of time and dose. At higher doses of abrin there was a decrease in hemoglobin level and RBC count which is reflected by increased levels of serum ammonia and bilirubin. Neutrophil infiltration in the liver and lipid peroxidation cause liver toxicity (increased production of ALT and ALP); oxidative stress (depletion of GSH and total antioxidant status); inflammation (increased production of TNF-α and IFN-γ). Further, at higher doses of abrin, intensity of oxidative stress, inflammation and liver toxicity are more pronounced which may have been maintained by the self-sustaining loop of toxicity leading to death of the animals.

Sexual dimorphism in rat thymic involution: a correlation with thymic oxidative status and inflammation.

The study investigated mechanisms underlying sex differences in thymic involution in Dark Agouti rats. Adverse effects of aging on thymus were more pronounced in males than in females. Thymi from old males exhibited more prominent: (i) fibro-adipose degeneration which correlated with greater intensity of thymic oxidative stress and enhanced thymic TGF-β and IL-6 expression and (ii) decline in thymopoiesis, as suggested by the number of the most mature CD4+CD8-/CD4-CD8+ single positive (SP) TCRαβhigh thymocytes. The greater accumulation of adipose tissue in old male thymus was linked with greater age-related increase in thymic expression of PPARγ and STAT3, a transcription factor regulating the expression of PPARγ downstream genes, in male than in female rats. In aged thymi of both sexes the early CD4-CD8- double negative (DN) stage of thymocyte development was affected, so relative accumulation of the least mature CD45RC+CD2- cells followed by decreased frequency of their DN and CD4+CD8+ double positive (DP) TCRαβ- descendants was observed. Additionally, in old males, because of the increased thymic expression of Nur77, a nuclear receptor involved in negative selection, and decreased CD90 (a negative regulator of thymocyte selection threshold) MFI on DP TCRαβint thymocytes, less efficient positive/more efficient negative selection was found. Moreover, in male rats, thymocyte post-selection differentiation/maturation was skewed towards CD4-CD8+ SP TCRαβhigh cells compared with age-matched females, reflecting, at least partly, greater IL-15 expression in their thymi. The study indicated mechanisms underlying sex-based differences in age-related thymic changes and consequently necessity of sex-specific approaches in designing strategies to rejuvenate thymus.

The therapeutic impact of entresto on protecting against cardiorenal syndrome-associated renal damage in rats on high protein diet

Background: This study tested the hypothesis that Entresto could safely and effectively preserve heart and kidney function in rats with cardiorenal syndrome (CRS) induced by 5/6 nephrectomy and intra-peritoneal doxorubicin administration (accumulated dosage up to 7.5 mg/kg) together with daily high-protein-diet (HPD).Methods and Results: Adult male Sprague-Dawley rats (n = 24) were equally categorized into Group 1 (sham-operated control + HPD), Group 2 (CRS + HPD) and Group 3 [CRS + HPD + Entresto (100 mg/kg/day orally) since Day 14 after CRS induction] and euthanized by Day 63 after CRS induction. By Day 63, circulatory BUN and creatinine levels and ratios of urine protein to creatinine were significantly higher in Group 2 than those in Groups 1 and 3, and significantly higher in Group 3 than in Group 1, whereas left-ventricular ejection fraction and kidney weight showed an opposite pattern among all groups (all p < 0.001). Microscopically, fibrosis area and intensity of oxidative stress (i.e., DCFDA stain) in kidney/heart tissues exhibited a pattern identical to that of creatinine level among all groups (all p < 0.0001). Kidney injury score and protein expressions of autophagy (i.e., beclin-1/Atg-5/protein ratio of LC3-BII/LC3-BI), fibrosis (Smad3/TGF-ß), apoptosis (mitochondrial-Bax/capase2/3/9), oxidative-stress (NOX-4/oxidized protein/xanthine-oxidase/catalase), membranous p47phox phosphorylation and mitochondrial-damage biomarker (cytosolic-cytochrome-C) were higher in Group 2 than those in Groups 1 and 3, and significantly higher in Group 3 than in Group 1, while protein expressions of anti-apoptosis (Bcl-2/Bcl-XL) and mitochondrial integrity (mitochondrial-cytochrome-C) markers displayed an opposite pattern among all groups in kidney tissues (all p < 0.0001).Conclusion: Oral administration of entresto was safe and could offer protection against CRS-induced heart and kidney damage.

Effect of hyperoxia on the immune status of oxygen divers and endurance athletes

Physical activity, particularly that, exerted by endurance athletes, impacts the immune status of the human body. Prolonged duration and high-intensity endurance training lead to increased production of reactive oxygen species (ROS) and thereby to oxidative stress. Military combat swimmers (O2-divers) are regularly exposed to hyperbaric hyperoxia (HBO) in addition to intensive endurance training intervals. They are, therefore, exposed to extreme levels of oxidative stress. Several studies support that the intensity of oxidative stress essentially determines the effect on immune status. The aim of this study was to comparatively characterise peripheral blood mononuclear cells (PBMCs) of O2-divers (military combat swimmers), endurance athletes (amateur triathletes), and healthy control volunteers with respect to DNA fragmentation, immune status and signs of inflammation. Furthermore, it was investigated how PBMCs from these groups responded acutely to exposure to HBO. We showed that DNA fragmentation was comparable in PBMCs of all three groups under basal conditions directly after HBO exposure. However, significantly higher DNA fragmentation was observed in O2-divers 18 hours after HBO, possibly indicating a slower recovery. O2-divers also exhibited a proinflammatory immune status exemplified by an elevated number of CD4+CD25+ T cells, elevated expression of proinflammatory cytokine IL-12, and diminished expression of anti-inflammatory TGF-β1 compared to controls. Supported by a decreased basal gene expression and prolonged upregulation of anti-oxidative HO-1, these data suggest that higher oxidative stress levels, as present under intermitted hyperbaric hyperoxia, e.g. through oxygen diving, promote a higher inflammatory immune status than oxidative stress through endurance training alone.

Design and characterization of a novel Arthrospira platensis glutathione oxido-reductase-derived antioxidant peptide GM15 and its potent anti-cancer activity via caspase-9 mediated apoptosis in oral cancer cells

Glutathione oxido-reductase (GR) is a primary antioxidant enzyme of most living forms which protects the cells from oxidative metabolism by reducing glutathione (GSH) from its oxidized form (GSSG). Although the antioxidant role of the enzyme is well characterized, the specific role of conserved N' peptide sequence in antioxidant mechanism remains unclear. In this study, we have identified an RNA sequence encoding GR enzyme from spirulina, Arthrospira platensis (Ap) and the changes in its gene expression profile was analysed during H2O2 stress. Results showed that H2O2 (10 mM) stimulated the expression of ApGR throughout the timeline of study (0, 5, 10, 15 and 20 days) with highest expression at 5th day post-exposure which confirmed the antioxidant role of ApGR in spirulina during H2O2 induced oxidative stress. A dithiol containing short antioxidant peptide, 39GGTCVIRGCVPKKLM53 (GM15) from ApGR was predicted and its radicals (superoxide and hydroxyl radical) scavenging potential was confirmed by in vitro cell-free assays. GM15 (12.5 μM) reduced the intracellular generalized oxidative stress level, as measured using DCFDA assay in H2O2 exposed leucocytes without affecting any of the cellular population. Further, the biomedical application of the radical scavenging property of GM15 was validated in oral carcinoma (KB) cells where GM15 exhibited significant cytotoxicity. Also, GM15 exhibited heterogenous effects on intracellular oxidative stress level in KB cells: at lower concentration (6.25 μM), the peptide reduced oxidative stress whereas, at higher concentration (25 μM) it increased the intensity of oxidative stress. GM15 (25 μM) induced caspase-9 mediated apoptosis in KB cells along with membrane disruption and DNA degradation which are confirmed by propidium iodide (PI) internalization and comet assays, respectively. Overall, the study shows that GM15 peptide i) scavenges superoxide, hydroxyl radicals, and influences intracellular oxidative stress, and ii) has anti-cancer effect in oral cancer cells.

Nicotine dependence as an independent risk factor for atherosclerosis in the National Lung Screening Trial

BackgroundAtherosclerosis and COPD are systemic inflammatory diseases that share common risk factors including cigarette smoking. A high level of nicotine dependence is emerging as a recently identified risk factor for pulmonary impairment, chronic obstructive pulmonary disease and tobacco-related cancers. We hypothesized that nicotine dependence is associated with the risk of atherosclerosis in long-term cigarette smokers.MethodsA nested case-control study was conducted within the National Lung Cancer Screening Trial- American College of Radiology Imaging Network. Cases were defined as having a new diagnosis of any type of atherosclerosis. Controls were matched on a 2:1 basis by age, sex, race, study center, smoking status, years of smoking, and frequency of smoking. Dependence was measured by the time to first cigarette after awakening (TTFC).ResultsThe study included 166 cases and 286 controls. Compared to participants who smoked within 5 min after waking, the risk of atherosclerosis for participants who smoked an hour or more after waking was borderline non-significant (odds ratio = 0.49, 95% confidence intervals [CI] 0.23, 1.00). Findings were similar for men and women. For aortic atherosclerosis, the corresponding odds ratio was 0.24 (95% CI 0.08, 0.69). Hypertension was associated with an increased risk and body mass index was associated with a decreased risk of aortic atherosclerosis. The TTFC was unrelated to coronary atherosclerosis.ConclusionsCompared to smoking immediately after waking, delaying an hour or more reduces the risk of aortic atherosclerosis even among long-term heavy smokers. Possible mechanisms that explain this association are intensity of smoking, inflammation and oxidative stress, and elevated lipid levels.

Social rank, color morph, and social network metrics predict oxidative stress in a cichlid fish

Dominance hierarchies are a fundamental part of social systems in many species and social rank can influence access to resources and impact health and physiology. While social subordination is a profound stressor, few studies consider the social stress experienced by dominant males due to constantly needing to defend their dominance status through costly aggressive displays. Recent studies suggest that in species that use body coloration to signal status, these costs may also be color morph-specific. Our study examines the link between the social rank, intensity of territorial defense, body coloration, and oxidative stress in males of the color polymorphic cichlid fish Astatotilapia burtoni where males are either blue or yellow. We studied behavior in naturalistic communities and examined circulating reactive oxygen metabolites (ROMs) and antioxidant defenses. We found that dominant males experience higher concentrations of circulating ROMs without notably increasing their antioxidant defenses, but this effect was not related to color morph. Aggression and social network ties predicted oxidative stress in a morph-specific manner, with yellow but not blue males showing signs of increased oxidative damage with increasing agonistic effort. In contrast to expectation, oxidative stress was not influenced by cortisol or testosterone levels. We conclude that oxidative stress is instrumental to understanding the costs and benefits of high social rank. Living in a social hierarchy can be stressful even for those on top. While past work has established the stress involved in being a low-ranking member of a hierarchy, we show that while high-ranking males attain definite advantages in terms of decreased stress hormone levels and increased reproductive opportunities, they also pay for their increased activity level with increased risk of cellular damage.

Fatty acid levels alterations in THP-1 macrophages cultured with lead (Pb)

ObjectiveAs cardiovascular events are one of the main causes of death in developed countries, each factor potentially increasing the risk of cardiovascular disease deserves special attention. One such factor is the potentially atherogenic effect of lead (Pb) on lipid metabolism, and is significant in view of the still considerable Pb environmental pollution and the non-degradability of Pb compounds. MethodsAnalysis of saturated fatty acids (SFA) (caprylic acid (C8:0), decanoic acid (C10:0), lauric acid (C12:0), tridecanoic acid (C13:0), myristic acid (C14:0), pentadecanoic acid (C15:0), palmitic acid (C16:0), heptadecanoic acid (C17:0), stearic acid (C18:0), and behenic acid (C22:0)), monounsaturated fatty acid (MUFA) (palmitoleic acid (C16:1), oleic acid (18:1w9), trans-vaccenic acid (C18:1 trans11)), and polyunsaturated fatty acid (PUFA) (linoleic acid (C18:2n6), gamma-linolenic acid (C18:3n6), arachidonic acid (C20:4n6)), was conducted by gas chromatography. Analysis of stearoyl-CoA desaturase (SCD), fatty acid desaturase 1 (FADS1) and fatty acid desaturase 2 (FADS2) expression was performed using qRT-PCR. Oxidative stress intensity (malondialdehyde - MDA concentration) was measured using spectrophotometric method. Intracellular generation of reactive oxygen species (ROS) in macrophages was visualized by fluorescence microscopy and quantitatively measured by plate reader. ResultsPb caused quantitative alterations in FAs profile in macrophages; the effect was Pb-concentration dependent and selective (i.e. concerned only selected FAs). In general, the effect of Pb was biphasic, with Pb levels of 1.25 μg/dL and 2.5 μg/dL being stimulatory, and 10 μg/dL being inhibitory on concentrations of selected FAs. The most potent Pb concentration, resulting in increase in levels of 9 FAs, was 2.5 μg/dL, the Pb-level corresponding to the mean blood Pb concentrations of people living in urban areas not contaminated by Pb. Pb was found to exert similar, biphasic effect on the expression of FADS1. However, Pb decreased, in a concentration-dependent manner, the expression of SCD and FADS2. Pb significantly increased MDA and ROS concentration in macrophages. ConclusionEnvironmental Pb exposure might be a risk factor resulting in alterations in FAs levels, oxidative stress and increased MDA concentration in macrophages, which might lead to the formation of foam cells and to inflammatory reactions.