Aggravation Of Oxidative Stress Research Articles

Accumulation of Renal Fibrosis in Hyperuricemia Rats Is Attributed to the Recruitment of Mast Cells, Activation of the TGF-β1/Smad2/3 Pathway, and Aggravation of Oxidative Stress

Renal fibrosis is relentlessly progressive and irreversible, and a life-threatening risk. With the continuous intake of a high-purine diet, hyperuricemia has become a health risk factor in addition to hyperglycemia, hypertension, and hyperlipidemia. Hyperuricemia is also an independent risk factor for renal interstitial fibrosis. Numerous studies have reported that increased mast cells (MCs) are closely associated with kidney injury induced by different triggering factors. This study investigated the effect of MCs on renal injury in rats caused by hyperuricemia and the relationship between MCs and renal fibrosis. Our results reveal that hyperuricemia contributes to renal injury, with a significant increase in renal MCs, leading to renal fibrosis, mitochondrial structural disorders, and oxidative stress damage. The administration of the MCs membrane stabilizer, sodium cromoglycate (SCG), decreased the expression of SCF/c-kit, reduced the expression of α-SMA, MMP2, and inhibited the TGF-β1/Smad2/3 pathway, thereby alleviating renal fibrosis. Additionally, SCG reduced renal oxidative stress and mitigated mitochondrial structural damage by inhibiting Ang II production and increasing renal GSH, GSH-Px, and GR levels. Collectively, the recruitment of MCs, activation of the TGF-β1/Smad2/3 pathway, and Ang II production drive renal oxidative stress, ultimately promoting the progression of renal fibrosis in hyperuricemic rats.

A Pilot Study of Influence of Endurance Training on the Prooxidative and Antioxidant Status of Women after Breast Cancer.

The objective of this study was to assess the effect of 8-week long endurance training on the prooxidative–antioxidative status of plasma in women treated for breast cancer. The participants of the study were 12 women after radical mastectomy aged 45 to 56 years (M = 50.6 ± 2.9 years), who had undergone full cancer treatment, on average more than 5 years after the treatment (M = 5.9 ± 0.9 years). Body mass components were measured twice using the method of bioelectric impedance analysis. In order to optimize training loads and to assess the level of exercise tolerance of the participants, the group was subject to an ergospirometric exercise test twice, before (1st) and after (2nd) the completion of the training cycle. The blood was also taken twice for biochemical analyses. Statistically significant differences were noted in the maximum exercise load, the level of which increased in the second test (p < 0.05). No change was observed in the level of antioxidative potential, i.e., the content of some variables, ferric reducing ability of plasma (FRAP), urea, total phenolics, thiobarbituric acid reactive substances (TBARS), and in the blood indices of the body’s nutritional status during the project (total protein, albumin. Endurance training caused an increase in exercise tolerance and did not cause an aggravation of oxidative stress in women undergoing breast cancer treatment.

Farming largemouth bass (Micropterus salmoides) with lettuce (Lactuca sativa) and radicchio (Cichorium intybus) in aquaponics: effects of stocking density on fish growth and quality, and vegetable production

Submitted 2020-06-30 | Accepted 2020-09-01 | Available 2020-12-01 https://doi.org/10.15414/afz.2020.23.mi-fpap.79-87 The present study assessed the effects of two initial stocking densities (low – LD, 4.23 kg m-3, moderate – MD, 8.05 kg m-3) on growth, health and fillet quality of largemouth bass (Micropterus salmoides), and on yield of lettuce (Lactuca sativa) and radicchio (Cichorium intybus group Rubifolium) produced in a low-tech recirculating aquaponic system. A total of 104 largemouth bass (initial body weight: 236 ± 38 g) were randomly stocked in eight 500 L tanks (four per stocking density) and monitored during a 70-day period. Vegetables yield was similar in LD and MD groups. Lettuce yield (6.33 kg m-2) was in line with typical values, whereas radicchio showed a negligible yield (1.34 kg m-2). Likewise, fish final weight (263 g, on average), specific growth rate (0.17% d-1), feed conversion ratio (2.72), and mortality (4.8%) did not differ between treatments. Fish morphometric indices, slaughter results and fillet quality were not affected by stocking density. In conclusion, the production of lettuce was successful in the tested system, whereas the production of radicchio did not achieve satisfactory results. Growth performances of the largemouth bass were poor and further investigations are required to optimize the rearing of this fish species in low-tech aquaponic systems. Keywords: largemouth bass, lettuce, radicchio, water quality, flesh quality References BAßMANN, B. et al. (2017). Stress and welfare of African catfish (Clarias gariepinus Burchell, 1822) in a coupled aquaponic system. Water, 9(7), 504. https://doi.org/10.3390/w9070504 BROWN, T. G. et al. (2009). Biological synopsis of largemouth bass (Micropterus salmoides). Canadian Manuscript Report of Fisheries and Aquatic Sciences, 2884, v + 27 p. CHAVES-POZO, E. et al. (2019). An overview of the reproductive cycle of cultured specimens of a potential candidate for Mediterranean aquaculture, Umbrina cirrosa. Aquaculture, 505, 137–149. https://doi.org/10.1016/j.aquaculture.2019.02.039 CHEN, Y. et al. (2020). Effects of dietary fish oil replacement by soybean oil and L-carnitine supplementation on growth performance, fatty acid composition, lipid metabolism and liver health of juvenile largemouth bass, Micropterus salmoides. Aquaculture, 516, 734596. https://doi.org/10.1016/j.aquaculture.2019.734596 PANTANELLA, E. et al. (2012). Aquaponics vs. hydroponics: production and quality of lettuce crop. Acta Horticulturae, 927, 887-893. https://doi.org/10.17660/ActaHortic.2012.927.109 RAHMAN, M. M (2015). Role of common carp (Cyprinus carpio) in aquaculture production systems. Frontiers in Life Science, 8(4), 399–410. https://doi.org/10.1080/21553769.2015.1045629 RAKOCY, J. E. (2012). Aquaponics: integrating fish and plant culture. In: Tidwell J.H. (Ed), Aquaculture production systems. India: Wiley-Blackwell (pp. 343–386). https://doi.org/10.1002/9781118250105.ch14 SAS (Statistical Analysis System). 2013. SAS/STAT(R) 9.2 User’s Guide, second ed. SAS Institute Inc., Cary, NC, USA. Retrieved May 10, 2020 from http://support.sas.com/documentation/cdl/en/statug/63033/HTML/default/viewer.htm#glm_toc.htm SOMERVILLE, C. et al. (2014). Small-scale aquaponic food production. Integrated fish and plant farming. Rome: FAO Fisheries and Aquaculture Technical Paper No. 589. Retrieved May 15, 2020 from http://www.fao.org/3/a-i4021e.pdf SUÁREZ, M. D. et al. (2014). Influence of dietary lipids and culture density on rainbow trout (Oncorhynchus mykiss) flesh composition and quality parameter. Aquaculture Engineering, 63, 16–24. http://dx.doi.org/10.1016/j.aquaeng.2014.09.001 SUN, J.-L. et al. (2020). Interactive effect of thermal and hypoxia on largemouth bass (Micropterus salmoides) gill and liver: Aggravation of oxidative stress, inhibition of immunity and promotion of cell apoptosis. Fish &amp; Shellfish Immunology, 98, 923–936. https://doi.org/10.1016/j.fsi.2019.11.056 TIDWELL, J. H. et al. (2000). Species profile – Largemouth bass. Southern Regional Aquaculture Center 722. Retrieved May 20, 2020 from http://aquaculture.ca.uky.edu/aquaculture-publications/12 TIDWELL, J. H. et al. (2007). Effect of stocking density on growth and water quality for largemouth bass Micropterus salmoides growout in ponds. Journal of the World Aquaculture Society, 29, 79–83. https://doi.org/10.1111/j.1749-7345.1998.tb00302.x TYSON, R. V. et al. (2004). Reconciling water quality parameters impacting nitrification in aquaponics: the pH levels. In: Proceedings of the Florida State Horticultural Society 117, 79–83. Retrieved May 20, 2020 from https://journals.flvc.org/fshs/article/view/858557_11 VITULE, J. R. S. et al. (2006). Introduction of the African catfish Clarias gariepinus (Burchell, 1822) into Southern Brazil. Biological Invasions, 8, 677–681. https://doi.org/10.1007/s10530-005-2535-8 WANG, Y. et al. (2019). Effect of stocking density on growth, serum biochemical parameters, digestive enzymes activity and antioxidant status of largemouth bass, Micropterus salmoides. Pakistan Journal of Zoology, 51(4), 1509–1517. http://dx.doi.org/10.17582/journal.pjz/2019.51.4.1509.1517 WATTS, C. et al. (2016). Evaluation of stocking density during second‐year growth of largemouth bass, Micropterus salmoides, raised indoors in a recirculating aquaculture system. Journal of the World Aquaculture Society, 47(4), 538–543. https://doi.org/10.1111/jwas.12315 YILDIZ, H. Y. et al. (2017). Fish welfare in aquaponic systems: its relation to water quality with an emphasis on feed and faeces—A review. Water, 9(1), 13. https://doi.org/10.3390/w9010013 YUAN, J. et al. (2019). Analysis of the growth performances, muscle quality, blood biochemistry and antioxidant status of Micropterus salmoides farmed in in-pond raceway systems versus usual-pond systems. Aquaculture, 511, 734241. https://doi.org/10.1016/j.aquaculture.2019.734241 Â

Relationships among pancreatic beta cell function, the Nrf2 pathway, and IRS2: a cross-sectional study

ABSTRACT Objectives This study aimed to investigate the relationships among islet function, the Nrf2 pathway, and insulin receptor substrate 2 (IRS2) in type 2 diabetes mellitus (T2DM), prediabetes mellitus (IGR), and normal glucose tolerance (NGT) populations. Methods Three hundred cases each were selected for the NGT, IGR, and T2DM groups; FBG, 2hPG, HbA1 c, FINS, TG, TC, HDL-C, and LDL-C levels and serum levels of nuclear factor in E2-related factor 2 (Nrf2), insulin receptor substrate 2 (IRS2), tumor necrosis factor alpha (TNF-α), and heme oxygenase 1 (HO-1) were evaluated. Results The T2DM group had lower islet β-cell function index and insulin sensitivity index than the NGT and IGR groups (P < 0.05). The Nrf2, IRS2, and HO-1 levels in the NGT, IGR, and T2DM groups followed a decreasing trend in the order mentioned, whereas the TNF-α levels followed an increasing trend. Conclusions Upon impairment of glucose regulation, the expression of TNF-α in the human body increased, which indicated the aggravation of oxidative stress (OS) and the inflammatory response. Islet function was maintained in the pre-diabetic population, and concurrently, the TNF-α, Nrf2, and HO-1 levels were moderately elevated, the expression of IRS2 was marginally inhibited, and the Nrf2 pathway was activated under mild OS stimulus to resist OS, inflammation, and injury, which may have been mediated through PI3 K/AKT. In patients with T2DM, islet function was significantly poorer, TNF-α amplification was enhanced significantly, and Nrf2, HO-1, and IRS2 expression reduced significantly; this suggested that, along with the aggravation of OS and the inflammatory response, Nrf2 pathway activation and HO-1 expression were both inhibited, the antioxidant capacity of the body was reduced, IRS2 degradation increased, and islet function was impaired.

Keap1-Nrf2 signaling pathway in angiogenesis and vascular diseases.

The transcription factor, nuclear factor E2-related factor 2 (Nrf2), is highly sensitive to oxidative burst products, including reactive oxygen species (ROS) and reactive nitrogen species. In the cell nucleus, Nrf2 activates various antioxidant genes by binding to the antioxidant response elements. As an adapter for cullin 3/ring-box 1, kelch-like ECH-associated protein 1 (Keap1) ubiquitinates and degrades Nrf2 under physiological conditions. Conversely, with the aggravation of oxidative stress, Keap1-Nrf2 interaction could be much more easily dissociated. ROS play a key role in regulating the redox signaling pathway and affect the vasculature in a dose-dependent manner. Long-term production or high concentration of ROS are harmful to the vascular system, while moderate ROS can promote angiogenesis and tissue regeneration. Furthermore, appropriate regulation of oxidative stress mediated via the Keap1-Nrf2 pathway would be beneficial in various diseases associated with abnormal angiogenesis, including diabetes and cancers. Nrf2 deficiency has also been shown to result in significantly impaired survival, proliferation, and angiogenic capacity of endothelial cells in a hind limb ischemia model. Thus, this review will briefly summarize the underlying molecular mechanisms of Keap1-Nrf2 pathway in regulating oxidative stress and also help elucidate the critical role of Keap1-Nrf2 in angiogenesis under physiological and pathological conditions.

Interactive effect of thermal and hypoxia on largemouth bass (Micropterus salmoides) gill and liver: Aggravation of oxidative stress, inhibition of immunity and promotion of cell apoptosis

High temperatures and low oxygen in aquatic environments, such as intensive aquaculture or in natural watersheds, inevitably cause stress in fish. Fish are exposed to high temperatures during the summer, which exacerbates hypoxia. Hypoxia (1.2 ± 0.2 mg/L) under 20 °C (20 HG) and 26 °C (26 HG) was simulated to induce stress in largemouth bass (Micropterus salmoides). Related enzymes and genes involved in antioxidant, immune, and apoptotic responses were selected to explore the interactive effects of temperature and hypoxia on largemouth bass. The results showed that malondialdehyde (MDA) levels in plasma, gill, and liver increased in the 26 HG (p < 0.05). Liver superoxide dismutase (SOD) activity increased in the 26 HG. Peak SOD (SOD1, SOD2, SOD3a, and SOD3b), CAT, and GSH-Px mRNA levels in the gill and liver were observed at 12–24 h of stress. The levels of gill and liver total antioxidant capacity, catalase (CAT), glutathione peroxidase (GSH-Px) activities and other enzyme activities and genes in the 26 HG were higher than those in the 20 HG (p < 0.05). The gill and liver acid phosphatase and alkaline phosphatase activities increased with time in the 26 HG (p < 0.05), while gill and liver lysozyme activities in the 26 HG were lower than those in the 20 HG (p < 0.05). Tumor necrosis factor-α mRNA level was upregulated in the gill and downregulated in the liver at 24 h in the 26 HG. Interleukin (IL)-1β and IL-8 mRNA levels were upregulated in the gill and liver in the 26 HG at 24 h, whereas IL-15 mRNA level was downregulated in the 26 HG at 12 h. Transforming growth factor-β1 mRNA level was upregulated in the gill in the 20 HG at 24 h, but downregulated in gill and liver in the 26 HG at 24 h. Similarly, IL-10, Hepcidin-1, and Hepcidin-2 showed lower expression levels in the 26 HG. Gill and liver caspase-3 activities were higher in the 26 HG (p < 0.05), and gill caspase-3 activity was higher than that in the liver. The mRNA levels of proapoptotic genes (caspase-3, caspase-8, and caspase-9) were higher in the 26 HG. The present study demonstrates the interactive effects of temperature and hypoxia on stress in largemouth bass gill and liver. These results will be helpful to understand the mechanisms of stress induced by temperature and hypoxia in fish and provide a theoretical basis for aquaculture management.

Physical Fatigue and Morphofunctional State of the Myocardium in Experimental Chronic Stress.

The relationship between the development of skeletal muscle fatigue of a specific type in male Wistar rats and morphofunctional alterations in the myocardium in the posttraumatic stress disorder (PTSD) model has been investigated for the first time. The aggravation of oxidative stress in the cardiomyocytes and the related transformation of the cell structural components and the depletion of energy reserves in PTSD has been identified as one of the main factors that accelerate the onset of musculoskeletal fatigue.

PO-133 Effects of different concentrations of hydrogen on oxidative stress in rats with high intensity exercise

Objective Exercise-induced oxidative stress is due to the massive increase in free radicals caused by strenuous exercise, which exceeds the ability of self-clearing. It is one of the main causes of sports injury and sports fatigue. Eliminating excessive production of free radicals is the key to alleviating exercise induced oxidative damage. Therefore, the purpose of this study is to study the effect of hydrogen on exercise-induced oxidative damage, to explore its possible mechanism and to explore the best dose of hydrogen with different concentrations.&#x0D; Methods 40 male SD rats (200±20g) were randomly divided into five groups(n=8):sedentary, exercise control, low concentration hydrogen with exercise(H1), medium concentration hydrogen with exercise(H2), high concentration hydrogen with exercise(H3). The rats performed high-intensity exercise for 4 weeks, except the sedentary. rats that with Low, medium and high concentration hydrogen were placed in a hydrogen atmosphere with a concentration of 0.5%, 1% and 1.5% for 1 h immediately after each exercise (keeping the concentration of oxygen and nitrogen in the environment the same as those in the air). The rats were weighed weekly during the experiment. The next day after 4 weeks of training, the samples were collected, and the contents of total superoxide dismutase (T-SOD), catalase (CAT), total antioxidant capacity (T- AOC) and malondialdehyde (MDA) were determined respectively.&#x0D; Results The weight of exercise control was significantly lower than sedentary in the third and fourth weeks of exercise (P&lt;0.05). Compared to sedentary rats, there was no significant difference in the weight of rats between H1, H2 and H3 group. The contents of T-AOC, CAT and T-SOD in exercise control were significantly higher than those in sedentary (P&lt;0.05). The content of CAT in H2 group was significantly decreased compared with exercise control (P&lt;0.01). Compared with exercise control, the T-AOC and T-SOD in the H2 group showed a downward trend but no statistical difference (P&gt;0.05), there was no significant difference between the above indexes, compared with sedentary. In addition, there was no difference in T-SOD and CAT content between H1 group and exercise control; Compared with exercise control, there was no significant difference in T-SOD, T-AOC and CAT in H3 group. At the MDA level, each exercise group increased significantly compared with the sedentary (P&lt;0.05), and the MDA levels in the H1, H2, and H3 groups were decreased compared with the exercise control, but there was no statistical difference.&#x0D; Conclusions It can be seen from the above results that different concentrations of hydrogen intervention can improve the weight loss of rats after intensive exercise. More importantly, the dosage and effect of 1% concentration of hydrogen is easier to remove the excessive radicals produced by intense exercise in the body, avoid the aggravation of oxidative stress, and have very good therapeutic effect. It provides a theoretical basis for the further study of the application of hydrogen in exercise oxidative damage.

Titanium dioxide nanoparticle-induced cytotoxicity and the underlying mechanism in mouse myocardial cells

Exposure to fine particulate matter (PM) is known to cause cardiovascular disease. While extensive research has focused on the risk of atmospheric PM to public health, particularly heart disease, limited studies to date have attempted to clarify the molecular mechanisms underlying myocardial cell damage caused by exposure to titanium dioxide nanoparticles (TiO2 NPs). Data from the current investigation showed that TiO2 NPs are deposited in myocardial mitochondria via the blood circulation accompanied by obvious ultrastructural changes and impairment of mitochondrial structure and function in mouse myocardial cells, including reduction in mitochondrial membrane potential and ATP production, aggravation of oxidative stress along with increased levels of reactive oxygen species, malondialdehyde and protein carbonyl, and decreased glutathione content and enzymatic activities, including superoxide dismutase and glutathione peroxidase. Furthermore, TiO2 NPs induced a significant decrease in the activities of complex I, complex II, complex III, complex IV, succinate dehydrogenase, NADH oxidase, Ca2+-ATPase, Na+/K+-ATPase, and Ca2+/Mg2+-ATPase, and upregulation of cytokine expression (including cytochrome c, caspase-3, and p-JNK) in mitochondria-mediated apoptosis while downregulating Bcl-2 expression in mouse myocardial cells. Our results collectively indicate that chronic exposure to TiO2 NPs induces damage in mitochondrial structure and function as well as mitochondria-mediated apoptosis in mouse myocardial cells, which may be closely associated with heart disease in animals and humans.

Proteomic Analysis of Mitochondria-Enriched Fraction Isolated from the Frontal Cortex and Hippocampus of Apolipoprotein E Knockout Mice Treated with Alda-1, an Activator of Mitochondrial Aldehyde Dehydrogenase (ALDH2).

The role of different genotypes of apolipoprotein E (apoE) in the etiology of Alzheimer’s disease is widely recognized. It has been shown that altered functioning of apoE may promote 4-hydroxynonenal modification of mitochondrial proteins, which may result in mitochondrial dysfunction, aggravation of oxidative stress, and neurodegeneration. Mitochondrial aldehyde dehydrogenase (ALDH2) is an enzyme considered to perform protective function in mitochondria by the detoxification of the end products of lipid peroxidation, such as 4-hydroxynonenal and other reactive aldehydes. The goal of our study was to apply a differential proteomics approach in concert with molecular and morphological techniques to elucidate the changes in the frontal cortex and hippocampus of apolipoprotein E knockout (apoE−/−) mice upon treatment with Alda-1—a small molecular weight activator of ALDH2. Despite the lack of significant morphological changes in the brain of apoE−/− mice as compared to age-matched wild type animals, the proteomic and molecular approach revealed many changes in the expression of genes and proteins, indicating the impairment of energy metabolism, neuroplasticity, and neurogenesis in brains of apoE−/− mice. Importantly, prolonged treatment of apoE−/− mice with Alda-1 led to the beneficial changes in the expression of genes and proteins related to neuroplasticity and mitochondrial function. The pattern of alterations implies mitoprotective action of Alda-1, however, the accurate functional consequences of the revealed changes require further research.

200 - Aggravation of Oxidative Stress after Thioredoxin Reductase Deficiency Interrupts Starvation-Induced Autophagy through Oxidative Modification of Lysosomal Cathepsins

Oxidative damage and aggregation of cellular proteins is a hallmark of neurodegenerative diseases. Autophagy induction as a means for degradation of protein aggregates in lysosomes is an important vital process in normal conditions, and its interruption has been linked to neuronal cell death in these diseases. The importance of redox status of the cell in induction of autophagy has been linked to oxidative modification of cysteine groups in key molecular proteins. The cellular redox milieu is regulated by the availability of reduced glutathione and Thioredoxin system and is important in fine tuning of many cellular function including the autophagy machinery. Amongst the intricate network of many autophagy related proteins (ATGs), only ATG4 has been identified as a potential target of Trx; we therefore aimed to further investigate the role of Trx system in regulation of autophagy process. Using pharmacological and RNA-editing technology we show that exacerbation of oxidative stress after Trx-reductase deficiency in a model of nutritional stress in neuroblastoma SH-SY5Y cells interferes with autophagy progression and promotes apoptosis. This was associated with decreased protein-degradation in lysosomes due to altered lysosomal acidification and accumulation of autophagosomes. Previous studies have shown the critical role of low levels of ROS for normal induction of autophagy. Our study provides novel evidence that aggravated oxidative stress affects the final stages of autophagy by inhibiting lysosome maturation by modification of cathepsin processing. This provides a novel mechanistic link between protein aggregation and conversion of autophagy to apoptosis in SH-SY5Y cells.

Does the sympathetic nervous system contribute to the pathophysiology of metabolic syndrome?

The metabolic syndrome (MS), formally known as syndrome X, is a clustering of several risk factors such as obesity, hypertension, insulin resistance, and dislypidemia which could lead to the development of diabetes and cardiovascular diseases (CVD). The frequent changes in the definition and diagnostic criteria of MS are indications of the controversy and the challenges surrounding the understanding of this syndrome among researchers. Obesity and insulin resistance are leading risk factors of MS. Moreover, obesity and hypertension are closely associated to the increase and aggravation of oxidative stress. The recommended treatment of MS frequently involves change of lifestyles to prevent weight gain. MS is not only an important screening tool for the identification of individuals at high risk of CVD and diabetes but also an indicator of suitable treatment. As sympathetic disturbances and oxidative stress are often associated with obesity and hypertension, the present review summarizes the role of sympathetic nervous system and oxidative stress in the MS.

Renin-angiotensin system blockade and exercise-induced increase in aortic stiffness.

In physiological conditions, the cushioning function of central conduit arteries transforms the cyclic high-flow and pressure oscillations in the ascending aorta into continuous and low-pressure blood flow at the level of microcirculation. Aging and elevated blood pressure (BP) induces structural and functional changes in arterial wall viscoelastic properties, resulting in arterial stiffening. The latter is reflected in progressive impairment of the cushioning function of central arteries and is typically associated with the development of isolated systolic hypertension and left ventricular hypertrophy. Importantly, prospective cohort studies have demonstrated that arterial hardening represents a strong and independent predictor of all-cause and cardiovascular mortality in various diseased populations, including patients with essential hypertension. Current guidelines on the management of arterial hypertension recommend regular physical activity as a major nonpharmacologic treatment approach towards BP lowering and cardiovascular risk reduction. In contrast, several lines of evidence from clinical studies suggest that acute high-intensity exercise can transiently elevate the risk of fatal and nonfatal cardiovascular events, mainly in prediposed individuals with substrate of structural cardiovascular disease. The mechanistic background of this deleterious impact of acute exercise on the cardiovascular system remains largely unclear. Activation of the sympathetic nervous system, aggravation of oxidative stress, platelet activation, impaired coagulation and fibrinolysis, and acute deterioration of large artery elasticity represent some of the mechanisms that have been proposed to be involved. It has to be noted that the type, frequency, duration, and intensity of physical exercise, play an important role in the exercise-induced alterations on the cardiovascular system. In this regard, previous clinical studies that investigated the effects of acute exercise on arterial elasticity, provide variable results. Some studies have shown high-intensity exercise to be associated with an acute increase in stiffness of central conduit arteries in healthy individuals. In other clinical studies, maximal aerobic exercise was found not to acutely affect large artery elasticity in young healthy patients. In contrast to the above, other investigators observed a sustained and prolonged improvement in compliance of peripheral muscular-type arteries and no change in elasticity of central conduit arteries after submaximal acute exercise in healthy patients. In this issue of The Journal of Clinical Hypertension, Gkaliagkousi and coworkers add important information to our knowledge, in this area, by reporting the results of a clinical study that explored acute changes in aortic stiffness after a high-intensity aerobic exercise test: (1) in untreated hypertensive compared with normotensive individuals, and (2) in hypertensive patients after 3 months of treatment with the angiotensin receptor blocker (ARB), valsartan. The study included 25 young patients with never-treated, newly diagnosed, stage I hypertension and 15 ageand sexmatched healthy volunteers. The investigators performed a careful workup of patients prior to study enrollment, excluding patients with secondary causes of hypertension and patients with white-coat or masked hypertension by performing 24-hour ambulatory BP monitoring. Arterial stiffness was assessed by measuring carotid to femoral pulse wave velocity (cf-PWV) with the use of the Sphygmocor device (AtCor Medical, West Ryde, Australia) at maximal exercise and at 10, 30, and 60 minutes after the completion of a treadmill exercise test. At baseline exercise test, significant elevations in systolic BP were noted at maximal exercise in both, hypertensive patients and healthy controls, which returned to pre-exercise levels after 10 and 30 minutes of recovery, respectively. In contrast, diastolic BP was not significantly different during acute high-intensity exercise, in both study groups. With regards to exercised-induced changes in aortic stiffness, cf-PWV was significantly elevated at maximal exercise in the group of hypertensive patients but not in the group of healthy controls. Of importance, despite the post-exercise reduction in systolic BP levels, the increase in cf-PWV persisted, even after 30 minutes of recovery in hypertensive patients. As expected, systolic BP and cf-PWV levels at all 5 timepoints of the baseline exercise test were significantly higher in hypertensive patients than in controls. After completion of the baseline test, 15 hypertensive participants who had indications to receive BP-lowering therapy according to guidelines were included in a subsequent interventional phase of the study to receive treatment with valsartan 160 mg daily for 3 months. Valsartan treatment resulted in significant reductions in both office and ambulatory BP and all treated hypertensive patients achieved adequate BP control at study Address for correspondence: Pantelis E. Zebekakis, MD, PhD, Section of Nephrology and Hypertension, 1st Department of Medicine, AHEPA University Hospital, St. Kiriakidi 1, GR54636, Thessaloniki, Greece E-mail: pzebeka@med.auth.gr

Аутоімунна реакція проти нейроспецифічних білків та якість життя пацієнтів з уродженою вадою серця

The results of experimental investigation of autoimmune reaction targeted against neirospecific protein antigens in patients with congenital heart failure are presented. It is shown that titer for autoanibodies to these patients’ brain proteins is significantly higher compared with healthy persons. Elevation of titer of these autoantibodies is correlated with the ability to solve tasks for revealing complex analogies and decrease of life quality. Therefore, worsening of life quality and development of cognitive deficit in patients with cardiovascular diseases might be associated with autoimmune reaction against specific proteins of nervous tissue cells. The results obtained demonstrate that generation of autoantibodies in patients with congenital heart failure is linked with the cognitive deficit. One of the most important causes of cognitive decline could be hypoxia state due to surgery intervention. Consequences of hypoxia, in their turn, are accompanied by chronic oxidative stress. Molecular and cell injuries induced by free radicals are known to be the widely spread cause of various pathologies. Further investigations for validation of diagnostic hallmarks for estimation of the origin of progression of the cognitive deficit in patients with congenital heart failure are needed. These studies will allow clarifying mechanisms of influence of hypoxia-induced injuries associated with the aggravation of oxidative stress in nervous tissue cells. Understanding of relationship between decline of cognitive function and pathologies of cardiovascular system is necessary for more precise clinical diagnostics of the early prevention of possible complications and proper treatment of patients.

Binge alcohol consumption aggravates oxidative stress and promotes pathogenesis of NASH from obesity-induced simple steatosis.

The pathogenesis of nonalcoholic steatohepatitis (NASH) is a two-stage process in which steatosis is the "first hit" and an unknown "second hit." We hypothesized that "a binge" could be a "second hit" to develop NASH from obesity-induced simple steatosis. Thirty-week-old male Otsuka Long-Evans Tokushima fatty (OLETF) rats were administered 10 mL of 10% ethanol orally for 5, 3, 2, and 1 d/wk for 3 consecutive weeks. As control, male Otsuka Long-Evans Tokushima (OLET) rats were administered the same amount of alcohol. Various biochemical parameters of obesity, steatosis and NASH were monitored in serum and liver specimens in untreated and ethanol-treated rats. The liver sections were evaluated for histopathological alterations of NASH and stained for cytochrome P-4502E1 (CYP2E1) and 4-hydroxy-nonenal (4-HNE). Simple steatosis, hyperinsulinemia, hyperglycemia, insulin resistance, hypertriglycemia and marked increases in hepatic CYP2E1 and 4-HNE were present in 30-wk-old untreated OLETF rats. Massive steatohepatitis with hepatocyte ballooning was observed in the livers of all OLETF rats treated with ethanol. Serum and hepatic triglyceride levels as well as tumor necrosis factor (TNF)-α mRNA were markedly increased in all ethanol-treated OLETF rats. Staining for CYP2E1 and 4-NHE demonstrated marked increases in the hepatic tissue of all the groups of OLETF rats treated with ethanol compared with OLET rats. Our data demonstrated that "a binge" serves as a "second hit" for development of NASH from obesity-induced simple steatosis through aggravation of oxidative stress. The enhanced levels of CYP2E1 and increased oxidative stress in obesity play a significant role in this process.

Coal-burning endemic fluorosis is associated with reduced activity in antioxidative enzymes and Cu/Zn-SOD gene expression

To study the effect of fluorine on the oxidative stress in coal-burning fluorosis, we investigated the environmental characteristics of coal-burning endemic fluorosis combined with fluorine content surveillance in air, water, food, briquette, and clay binder samples from Bijie region, Guizhou Province, southwest of China. The activities of antioxidant enzymes including copper/zinc superoxide dismutase (Cu/Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and level of lipid peroxidation such as malondialdehyde (MDA) were measured in serum samples obtained from subjects residing in the Bijie region. Expression of the Cu/Zn-SOD gene was assessed by quantitative reverse transcriptase PCR (qRT-PCR). Our results showed that people suffering from endemic fluorosis (the high and low exposure groups) had much higher MDA level. Their antioxidant enzyme activities and Cu/Zn-SOD gene expression levels were lower when compared to healthy people (the control group). Fluorosis can decrease the activities of antioxidant enzymes, which was associated with exposure level of fluorine. Down-regulation of Cu/Zn-SOD expression may play an important role in the aggravation of oxidative stress in endemic fluorosis.

Elevated Asymmetric Dimethylarginine is Associated With Oxidant Stress Aggravation in Patients With Early Stage Autosomal Dominant Polycystic Kidney Disease

Background/Aims: In experimental models of polycystic kidney disease impaired bioavailability of nitric oxide (NO) and elevated mRNA expression of oxidative stress markers at the kidney level was noted. However, clinical studies investigating the potential role of endothelial dysfunction and oxidative stress in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) are limited. We evaluated asymmetric dimethylarginine (ADMA) as marker of NO synthase inhibitor as well as 15-F_2t-Isoprostane and oxidized-low density lipoprotein (oxidized-LDL) as measures of oxidative stress in patients with early stages ADPKD. Methods: We recruited 26 ADPKD patients (Group A) with modestly impaired renal function (eGFR 45-70 ml/min/1.73m²), 26 age- and sex-matched ADPKD patients (Group B) with relatively preserved renal function (eGFR)>70 ml/min/1.73m²), and 26 age- and sex-matched controls (Group C). Determination of circulating levels of ADMA, 15-F_2t-Isoprostane, oxidized-LDL and routine biochemistry was performed. Results: Group A and B had significantly higher ADMA levels as compared to controls (1.68±0.7 vs 0.51±0.2 μmol/l, P<0.001 and 1.26±0.7 vs 0.51±0.2 μmol/l, P<0.001, respectively). 15-F_2t-IsoP and oxidized-LDL levels were also significantly higher in Group B relative to controls (788.8±185.0 vs 383.1±86.0 pgr/ml, P<0.001 and 11.4±6.6 vs 6.4±2.6 EU/ml, P<0.05 respectively) and were further elevated in Group A. In correlation analysis, ADMA levels exhibited strong associations with levels of 15-F_2t-Isoprostane (r=0.811, P<0.001) and oxidized-LDL (r=0.788, P<0.001), whereas an inverse correlation was evident between ADMA and eGFR (r=-0.460, P<0.001). Conclusion: This study shows elevation in circulating levels of ADMA along with aggravation of oxidative stress from the early stages of ADPKD.

Superoxide in AVF dysfunction: a new target for intervention

an adequately functioning vascular access is an absolute requisite for patients receiving hemodialysis. Among the three currently available (fistulae, grafts, and tunneled catheters) vascular accesses, the arteriovenous fistula (AVF) is considered the “gold standard” and is the most common mode

Effect of fluoride on oxidative stress and Mn-SOD expression in rats with endemic fluorosis of coal burning

To study the effect of fluoride on the oxidative stress of the rats in endemic fluorosis of coal burning and Mn-SOD expression at mRNA and protein levels. SD rats were divided into 2 groups (the number of female and male in each group was the same): control group and fluorosis group. All rats of the fluorosis group were fed corn dried by burning coal from endemic fluorosis areas with high fluoride content (fluoride 17 mg/kg in feed) to establish an animal model of fluorosis. In these rats, dental fluorosis was evaluated. The fluoride content in the urine was measured by fluorine ion-elective electrode method. The hepatic tissue and serum level of malonaldehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathion reductase (GR) were measured by biochemical methods. The index signs of liver function were also measured from the serum. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were performed to detect the alterations of Mn-SOD expression in the liver at mRNA and protein levels. The dental fluorosis was observed in the fluorosis group, and the incidence was 11/11. The fluoride contents [(3.50 ± 2.58) mg/L] in the urine of fluorosis rats were increased as compared with the control [(1.42 ± 0.38) mg/L] (P < 0.05). AST [(223.74 ± 71.51) U/L] and total protein [(72.43 ± 5.59) g/L] of the hepatic function index in fluorosis rats showed obviously abnormal as compared with the control [(169.28 ± 53.74) U/L and (82.36 ± 7.31) g/L], respectively (P < 0.05). In the liver the content of MDA [(10.41 ± 0.59) µmol/g protein] increased as compared to the control [(5.80 ± 1.31) µmol/g protein, P < 0.01], and the activities of SOD [(62.60 ± 8.65) U/mg protein] and GR [ (1.17 ± 0.66) U/g protein] markedly decreased in the fluorosis group compared to the control [SOD (117.28 ± 8.64) U/mg protein and GR [(8.80 ± 1.59) U/g protein; P < 0.05, P < 0.01]. The level of Mn-SOD in the liver was markedly decreased in the fluorosis group [(14.83 ± 2.50) U/mg protein] as compared with the control [(34.05 ± 5.22) U/mg protein, P < 0.01]. The levels of mRNA (0.64 ± 0.15) and protein (0.84 ± 0.13) of Mn-SOD were markedly decreased in the fluorosis group as compared with the control [(0.86 ± 0.21) and (1.04 ± 0.14)], respectively (P < 0.05, P < 0.01). Fluorosis can decrease the activities of Mn-SOD, which is associated with decreased levels of mRNA and protein of Mn-SOD. Down-regulation of Mn-SOD expression may play an important role in the aggravation of oxidative stress in endemic fluorosis.

Correlation of Nitric Oxide and Other Free Radicals With the Severity of Acute Pancreatitis and Complicated Systemic Inflammatory Response Syndrome

To investigate the correlation of nitric oxide (NO) and other free radicals with the severity of acute pancreatitis (AP) and complicated systemic inflammatory response syndrome (SIRS). Fifty AP patients (24 simple AP patients and 26 patients with AP complicated by SIRS) were involved in the study. Fifty healthy volunteers were included as controls. Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were evaluated, and plasma NO, plasma lipid peroxides, plasma vitamin E, plasma beta-carotene, whole-blood glutathione (GSH), and the activity of plasma GSH peroxidase were measured. Compared with the control group, the APACHE II scores heightened in the AP group, and the SIRS group had the highest APACHE II scores (P < 0.005, P < 0.001, respectively). Plasma NO and plasma lipid peroxides increased with the heightening APACHE II scores, demonstrating a significant linear positive correlation (r = 0.618, r = 0.577, respectively; P < 0.001). Plasma vitamin E, plasma beta-carotene, whole-blood GSH, and the activity of plasma GSH peroxidase decreased with the heightening APACHE II scores, demonstrating a significant linear negative correlation (r = -0.600, r = -0.609, r = -0.559, r = -0.592, respectively; P < 0.001). Nitric oxide and other free radicals take part in the aggravation of oxidative stress and oxidative injury and may play important roles in the pathogenesis of AP and SIRS. It may be valuable to measure free radicals to predict the severity of AP.