End Products Of Oxidation Research Articles

PM2.5-induced lung injury is attenuated in macrophage-specific NLRP3 deficient mice

Fine particulate matter (PM2.5) is one of the most important components of environmental pollutants and is associated with lung injury. Pyroptosis, a form of programmed cell death mainly mediated by the NLRP3 inflammasome, has been reported to be involved in sepsis-induced or ischemia/reperfusion-induced lung injury. However, the specific mechanisms of pyroptosis in PM2.5-induced lung injury are not yet clear. We constructed macrophage-specific NLRP3 knockout mice to explore the mechanism of PM2.5-induced lung injury in terms of inflammatory response, oxidative stress, and apoptosis levels, including the relationship between these effects and pyroptosis. The results disclosed that PM2.5 exposure increased the infiltration of macrophages and leukocytes and the secretion of inflammatory cytokines, including TNF-α and IL-6, in lung tissue. The activity of antioxidant enzymes, including SOD, GSH-PX, and CAT, significantly decreased, while MDA, the end product of lipid oxidation, remarkably increased. The level of apoptosis in lung tissue, measured by the TUNEL assay and apoptosis-related proteins (BAX and BCL-2), was significantly increased. Macrophage-specific NLRP3 knockout could offset these effects. We further observed that PM2.5 treatment activated the NLRP3 inflammasome and subsequently induced pyroptosis, as evidenced by the increased production of IL-1β and IL-18 and the increase of the protein levels of NLRP3, ASC, caspase-1, and GSDMD, which were inhibited when NLRP3 was knocked out in macrophages. Taken together, these results revealed that NLRP3-mediated macrophage pyroptosis promoted PM2.5-induced lung injury through aggravating inflammation, oxidative stress, and apoptosis. Targeting the inhibition of NLRP3-mediated macrophage pyroptosis provides a new way to study lung injury induced by the exposure to PM2.5.

Bioflavonoid (Hesperidin) Restrains Protein Oxidation and Advanced Glycation End Product Formation by Targeting AGEs and Glycolytic Enzymes.

Alpha-amylase (α-amylase) not long ago has acquire recognition as a possible drug target for the management of diabetes. Here, we have investigated the binding and enzyme activity of α-amylase by hesperidin; a naturally occurring flavanone having wide therapeutic potential. Hesperidin exerted an inhibitory influence on α-amylase activity with an IC50 value of 16.6 µM. Hesperidin shows a significant binding toward α-amylase with a binding constant (Ka) of the order of 104 M-1. The evaluation of thermodynamic parameters (∆H and ∆S) suggested that van der Waals force and hydrogen bonding drive seemingly specific hesperidin-α-amylase complex formation. Glycation and oxidation studies were performed using human serum albumin (HSA) as ideal protein. Hesperidin inhibited fructosamine content ≈40% at 50 µM and inhibited advanced glycation end products (AGEs) formation by 71.2% at the same concentration. Moreover, significant recovery was evident in free -SH groups and carbonyl content of HSA. Additionally, molecular docking also entrenched in vitro observations and provided an insight into the important residues (Trp58, Gln63, His101, Glu233, Asp300, and His305) at the heart of hesperidin-α-amylase interaction. This study delineates mechanistic insight of hesperidin-α-amylase interaction and provides a platform for use of hesperidin to treat AGEs directed diseases.

Catalytic Effects of Zeolite Socony Mobil-5 (ZSM-5) on the Oxidation of Acoustically Levitated exo-Tetrahydrodicyclopentadiene (JP-10) Droplets.

Jet propulsion 10 (JP-10) droplets with and without aluminum nanoparticles in conjunction with HZSM-5 zeolite and surfactants were ultrasonically levitated, and their oxidation processes were explored to identify how the oxidation process of JP-10 is catalytically affected by the HZSM-5 zeolites and how the surfactant and Al NPs in the system impacted the key experimental parameters of the ignition such as ignition delay time, burn rate, and the maximum temperatures. Singly levitated droplets were ignited using a carbon dioxide laser under an oxygen-argon atmosphere. Pure JP-10 droplets and JP-10 droplets with silicon dioxide of an identical size distribution as the zeolite HZSM-5 did not ignite in strong contrast to HZSM-5-doped droplets. Acidic sites were found to be critical in the ignition of the JP-10. With the addition of the surfactant, the characteristic features of the JP-10 ignition were improved, so the ignition delay time of the zeolite-JP-10 samples were decreased by 2-3 ms and the burn rates were increased by 1.3 to 1.6 × 105 K s-1. The addition of Al NPs increased the maximum temperatures during the combustion of the systems by 300-400 K. Intermediates and end products of the JP-10 oxidation over HZSM-5 were characterized by UV-vis emission and Fourier-transform infrared transmission spectroscopies, revealing key reactive intermediates (OH, CH, C2, O2, and HCO) along with the H2O molecules in highly excited rovibrational states. Overall, this work revealed that acetic sites in HZSM-5 are critical in the catalytic ignition of JP-10 droplets with the addition of the surfactant and Al NPs, enhancing the oxidation process of JP-10 over HZSM-5 zeolites.

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

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

Psoriasis, An inflammatory condition associated with oxidative stress

Background: Psoriasis is a chronic inflammatory skin disease characterized by pathological skin lesions due to various exogenous and endogenous factors. Oxidative stress can be one of the causes for the occurrence of psoriasis as well as significant contributor to its progression. Skin exposure to a number of irritants or proinflammatory agents including UVA and UVB generates ROS through the oxidative burst in infiltrating leukocytes at the site of inflammation which damages the skin cells. Measurement of the oxidative stress marker like lipid peroxidation product Malondialdehyde (MDA) and Nitric Oxide end products (NO2+NO3) along with the inflammatory marker hs-CRP in Psoriasis patients can uncover their role in disease causation, progression and development of various co-morbidities and timely prevention can significantly improve the quality of life of the psoriasis patients.
 Aims and Objectives: To measure the oxidative stress marker like lipid peroxidation product Malondialdehyde (MDA) and Nitric Oxide end products (NO2+NO3) along with the inflammatory marker hs-CRP in Psoriasis patients to uncover their role in disease causation, progression and development of various co-morbidities and timely prevention to significantly improve the quality of life of the psoriasis patients.
 Materials and Methods: Fifty patients of psoriasis mainly plaque type of either sex, in the age group of 35 ± 15.5 (range: 7-79) years were taken following inclusion and exclusion criteria. To evaluate the oxidative stress lipid peroxidation product malondialdehyde (MDA) and Nitric Oxide end products (NO2 + NO3) were measured. hs-CRP was measured as an inflammatory marker and their correlation with the disease severity and duration was evaluated.
 Results: A significant increase in malondialdehyde (MDA), Nitric Oxide end products (NOx) and hs-CRP levels (P<0.001) was noted in Psoriatic patients as compared to controls. There was a positive correlation between MDA, NOx and hs-CRP levels with the severity and duration of the disease. The correlation between hs-CRP and MDA and NOx also showed positive trend.
 Conclusion: Oxidative stress is one of the factors which can lead to the causation of Psoriasis and also significantly contribute to the disease progression and development of various co-morbidities. By measuring the oxidative stress marker and inflammatory marker in psoriasis patients early in the disease process we can employ preventive strategies for better management and improve the survival and quality of life.

Lipid profiling and dietary assessment of infant formulas reveal high intakes of major cholesterol oxidative product (7-ketocholesterol)

Approximately two-thirds of US infants receive infant formula (IF) as a primary or sole nutritional source during the first six months of life. IF is available in a variety of commercial presentations; from a manufacturing standpoint, they can be categorized as powder- (PIF) or liquid- (LIF) based formulations. Thirty commercial IFs were analyzed in their oxidative and non-oxidative lipid profiles. We identified 7-ketocholesterol – a major end-product of cholesterol oxidation – as a potential biomarker of IF manufacturing. The statistical analysis allowed a re-classification of IF based on their metabolomic fingerprint, resulting in three groups assigned with low-to-high oxidative status. Finally, we modeled the dietary intake of cholesterol, sterols, and 7-ketocholesterol in the first year of life. The database provided in this study will be instrumental for scientists interested in infant nutrition, to establish bases for epidemiological studies aimed to find connections between nutrition and diet-associated diseases, such as sitosterolemia.

Degradation of Acid Violet 19 textile dye by electro-peroxone in a laboratory flow plant

This paper deals with the degradation of Acid Violet 19 (AV19) textile dye by the electro-peroxone (E-peroxone) process in a laboratory flow plant using a filter press cell fitted with a 3D gas diffusion electrode (3D GDE) containing a graphite felt positioned on carbon-cloth PTFE as cathode, and a Ti|IrSnSb-oxides plate as anode. H2O2 was formed by the oxygen reduction reaction (ORR) in the cathode; the air was supplied by an external compressor. The O3 produced externally by an ozonator was added in the pipeline at the outlet of the electrolyzer to promote the reaction between the H2O2 and O3 to produce OH, which is the responsible for the mineralization of the dye. The effect of electrolyte flow rate (Q), current density (j), and initial concentration of AV19 dye on its degradation was addressed. The best electrolysis in a solution containing 40 mg TOC L−1, 0.05 M Na2SO4, at pH 3, was obtained at j = 20 mA cm−2, Q = 2.0 L min−1, using a pressure of the air fed to the 3D GDE of PGDE = 3 psi, and an ozone inlet mass flow rate of F03 = 14.5 mg L−1, achieving 100% discoloration, 60% mineralization, with mineralization current efficiency and energy consumption of 36% and 0.085 kWh(gTOC)−1. The degradation of AV19 dye was also performed by anodic oxidation plus H2O2 electrogenerated (AO-H2O2) and ozonation. The oxidation power was AO-H2O2 < ozonation < E-peroxone. Three carboxylic acids were quantified by chromatography as oxidation end products.

Effects of residual disinfectants on the redox speciation of lead(ii)/(iv) minerals in drinking water distribution systems.

This study investigated the reaction kinetics on the oxidative transformation of lead(ii) minerals by free chlorine (HOCl) and free bromine (HOBr) in drinking water distribution systems. According to chemical equilibrium predictions, lead(ii) carbonate minerals, cerussite PbCO3(s) and hydrocerussite Pb3(CO3)2(OH)2(s), and lead(ii) phosphate mineral, chloropyromorphite Pb5(PO4)3Cl(s) are formed in drinking water distribution systems in the absence and presence of phosphate, respectively. X-ray absorption near edge spectroscopy (XANES) data showed that at pH 7 and a 10 mM alkalinity, the majority of cerussite and hydrocerussite was oxidized to lead(iv) mineral PbO2(s) within 120 minutes of reaction with chlorine (3 : 1 Cl2 : Pb(ii) molar ratio). In contrast, very little oxidation of chloropyromorphite occurred. Under similar conditions, oxidation of lead(ii) carbonate and phosphate minerals by HOBr exhibited a reaction kinetics that was orders of magnitude faster than by HOCl. Their end oxidation products were identified as mainly plattnerite β-PbO2(s) and trace amounts of scrutinyite α-PbO2(s) based on X-ray diffraction (XRD) and extended X-ray absorption fine structure (EXAFS) spectroscopic analysis. A kinetic model was established based on the solid-phase experimental data. The model predicted that in real drinking water distribution systems, it takes 0.6-1.2 years to completely oxidize Pb(ii) minerals in the surface layer of corrosion scales to PbO2(s) by HOCl without phosphate, but only 0.1-0.2 years in the presence of bromide (Br-) due the catalytic effects of HOBr generation. The model also predicts that the addition of phosphate will significantly inhibit Pb(ii) mineral oxidation by HOCl, but only be modestly effective in the presence of Br-. This study provides insightful understanding on the effect of residual disinfectant on the oxidation of lead corrosion scales and strategies to prevent lead release from drinking water distribution systems.

Bilirubin Oxidation End Products (BOXes) Induce Neuronal Oxidative Stress Involving the Nrf2 Pathway.

Delayed ischemic neurological deficit (DIND) is a severe complication after subarachnoid hemorrhage (SAH). Previous studies have suggested that bilirubin oxidation end products (BOXes) are probably associated with the DIND after SAH, but there is a lack of direct evidence yet even on cellular levels. In the present study, we aim to explore the potential role of BOXes and the involved mechanisms in neuronal function. We synthesized high-purity (>97%) BOX A and BOX B isomers. The pharmacokinetics showed they are permeable to the blood-brain barrier. Exposure of a moderate concentration (10 or 30 μM) of BOX A or BOX B to isolated primary cortical neurons increased the production of reactive oxygen species. In the human neuroblastoma SH-SY5Y cells, BOX A and BOX B decreased the mitochondrial membrane potential and enhanced nuclear accumulation of the protein Nrf2 implicated in oxidative injury repair. In addition, both chemicals increased the mRNA and protein expression levels of multiple antioxidant response genes including Hmox1, Gsta3, Blvrb, Gclm, and Srxn1, indicating that the antioxidant response element (ARE) transcriptional cascade driven by Nrf2 is activated. In conclusion, we demonstrated that primary cortical neurons and neuroblastoma cells undergo an adaptive response against BOX A- and BOX B-mediated oxidative stress by activation of multiple antioxidant responses, in part through the Nrf2 pathway, which provides in-depth insights into the pathophysiological mechanism of DIND after SAH or other neurological dysfunctions related to cerebral hemorrhage.

Protective effect of Curculigo orchioides in streptozotocin and nicotinamide-induced diabetic neuropathic pain in Wistar rats

Pain, paraesthesia, sensory loss, and associated high morbidity and mortality are typically characterized by diabetic neuropathy (DN). Curculigo orchioides (CO) is a herbal medicine that is rich in flavonoids, glycosides, and polyphenols which are known for potential antioxidant activity. Moreover, the anti-hyperglycemic potential of CO paved the way for pharmacological investigation in the treatment of diabetic complications since the regulation of hyperglycemia is considered as a major factor in the treatment of diabetes. The current study was designed to evaluate the neuroprotective effect of CO extract in DN. DN was induced in rats using streptozotocin (STZ) (65 mg/kg, i.p.) after 15 minutes of nicotinamide (NAD; 230 mg/kg, i.p.). Diabetic rats showed significant mechanical, thermal hyperalgesia, and allodynia. Diabetic rats also showed increased oxidative stress parameters and advanced glycation end products (AGEs) formation. Oral treatment was started on 60th day after STZ–NAD administration and continued for the next 30 days, with different doses (150, 300, and 600 mg/kg) of CO extracts (ethanolic and hydroalcoholic) and standard drug gabapentin (30 mg/kg). The results of the study revealed that both extracts reduced hyperglycemia and inhibited the pain response partially via reduction of oxidative stress and AGEs formation in DN rats. Both the extracts reduced the neuropathic pain in diabetic rats at dose dependent manner.

The Impact of Methane on Microbial Communities at Marine Arctic Gas Hydrate Bearing Sediment.

Cold seeps are characterized by high biomass, which is supported by the microbial oxidation of the available methane by capable microorganisms. The carbon is subsequently transferred to higher trophic levels. South of Svalbard, five geological mounds shaped by the formation of methane gas hydrates, have been recently located. Methane gas seeping activity has been observed on four of them, and flares were primarily concentrated at their summits. At three of these mounds, and along a distance gradient from their summit to their outskirt, we investigated the eukaryotic and prokaryotic biodiversity linked to 16S and 18S rDNA. Here we show that local methane seepage and other environmental conditions did affect the microbial community structure and composition. We could not demonstrate a community gradient from the summit to the edge of the mounds. Instead, a similar community structure in any methane-rich sediments could be retrieved at any location on these mounds. The oxidation of methane was largely driven by anaerobic methanotrophic Archaea-1 (ANME-1) and the communities also hosted high relative abundances of sulfate reducing bacterial groups although none demonstrated a clear co-occurrence with the predominance of ANME-1. Additional common taxa were observed and their abundances were likely benefiting from the end products of methane oxidation. Among these were sulfide-oxidizing Campilobacterota, organic matter degraders, such as Bathyarchaeota, Woesearchaeota, or thermoplasmatales marine benthic group D, and heterotrophic ciliates and Cercozoa.

Tocilizumab mimotope alleviates kidney injury and fibrosis by inhibiting IL-6 signaling and ferroptosis in UUO model

AimsPreviously we identified four Tocilizumab mimotopes and antibodies induced by these mimotopes could bind to IL-6R (interleukin-6 receptor) and regulate the downstream signaling pathways. On the basis of obtained research data, we sought to investigate whether the therapeutic strategies by Tocilizumab mimotope vaccination could be effective in the renal fibrosis model and show the desired activity by inhibiting IL-6 signaling in current study. Main methodsWe immunized the mice with the Tocilizumab mimotope and then performed the unilateral ureteric obstruction (UUO) surgery. Masson-trichrome staining and immunohistochemistry were performed to evaluate the renal fibrosis. The activations and differentiations of F4/80+ cells in the spleens and kidneys were detected by flow cytometry, immunohistochemistry and immunofluorescence. Signaling pathways involved IL-6, pro-fibrotic and ferroptosis were analyzed by immunoblot assay. The free iron and lipid oxidation end product were performed by Prussian blue staining and immunohistochemistry. The injury and apoptosis in the kidneys were evaluated by immunofluorescence. Key findingsThe results showed the mimotope vaccination could reduce the level of fibrosis, injury and apoptosis by down-regulating the pro-fibrotic proteins, alleviating the activations and differentiations of macrophage F4/80+ cells in UUO models. IL-6/ERK signaling pathway was inhibited with the mimotope vaccination. The ferroptosis inhibited proteins significantly increased after the mimotope vaccination. On the contrary, the levels of free iron and lipid oxidation end product were observed to decrease in the mimotope treatment group. SignificanceOur results suggested that the Tocilizumab mimotope vaccination might be an alternative therapy to against renal fibrosis.

Changes in \u03b3H2AX and H4K16ac levels are involved in the biochemical response to a competitive soccer match in adolescent players

The aim of this study was to examine novel putative markers of the response to the competitive soccer match in adolescent players, such as changes in global levels of γH2AX and H4K16ac in the chromatin of peripheral mononuclear blood cells (PMBCs) and a Fourier-transform infrared spectroscopy (FTIR)-based biochemical fingerprint of serum. These characteristics were examined with reference to the physiological and metabolic aspects of this response. Immediately post-match we noticed: (1) a systemic inflammatory response, manifesting as peaks in leukocyte count and changes in concentrations of IL-6, TNFα, and cortisol; (2) a peak in plasma lactate; (3) onset of oxidative stress, manifesting as a decline in GSH/GSSG; (4) onset of muscle injury, reflected in an increase in CK activity. Twenty-four hours post-match the decrease in GSH/GSSG was accompanied by accumulation of MDA and 8-OHdG, macromolecule oxidation end-products, and an increase in CK activity. No changes in SOD1 or GPX1 levels were found. Repeated measures correlation revealed several associations between the investigated biomarkers. The FTIR analysis revealed that the match had the greatest impact on serum lipid profile immediately post-game. In turn, increases in γH2AX and H4K16ac levels at 24 h post-match indicated activation of a DNA repair pathway.

Влияние паразитарных инвазий на значения малонового диальдегида и церулоплазмина у лошадей

Parasitic invasions in horses often cause metabolic disorders and have a negative impact on their health and performance. The purpose of this research was to study the processes of lipid peroxidation and antioxidant protection in horse helminthiases, as well as following the deworming with a drug containing the antioxidant santoquine. The intensity of lipid peroxidation and antioxidant protection was determined in horses with different degrees of invasion by concentrations of malondialdehyde and ceruloplasmin accumulated in the blood. The studies have revealed that the concentration of malondialdehyde, the end product of free radical oxidation of cell membrane phospholipids, depends on the intensity of infestation with intestinal nematodes. In horses infested with paraskaris and intestinal strongylata, a significant accumulation of malondialdehyde was by 18.2% higher as compared to uninfected animals. The level of ceruloplasmin was significantly lower – by 21.8% in animals with a moderate degree of invasion as compared to clinically healthy animals. To neutralize free radicals the antioxidant santoquine was used. Effective deworming by means of using santoquine reduced the intensity of lipid peroxidation processes, which resulted in a significant decrease in the concentration of malondialdehyde by 22.1% and an increase in the level of ceruloplasmin against the background of the lower rate of free radical oxidation by 25.8%.

Polyphenols by Generating H2O2, Affect Cell Redox Signaling, Inhibit PTPs and Activate Nrf2 Axis for Adaptation and Cell Surviving: In Vitro, In Vivo and Human Health.

Human health benefits from different polyphenols molecules consumption in the diet, derived mainly by their common activities in the gastrointestinal tract and at the level of blood micro-capillary. In the stomach, intestine and colon, polyphenols act as reducing agents preventing lipid peroxidation, generation and absorption of AGEs/ALEs (advanced glycation end products/advanced lipid oxidation end products) and postprandial oxidative stress. The low absorption of polyphenols in blood does not support their activity as antioxidants and their mechanism of activity is not fully understood. The results are from in vitro, animal and human studies, detected by relevant oxidative stress markers. The review carries evidences that polyphenols, by generating H2O2 at nM concentration, exogenous to cells and organs, act as activators of signaling factors increasing cell Eustress. When polyphenols attain high concentration in the blood system, they generate H2O2 at µM concentration, acting as cytotoxic agents and Distress. Pre-treatment of cells or organisms with polyphenols, by generating H2O2 at low levels, inhibits cellular PTPs (protein tyrosine phosphatases), inducing cell signaling through transcription of the Nrf2 (nuclear factor erythroid 2-related factor 2) axis of adaptation and protection to oxidation stress. Polyphenols ingestion at the right amount and time during the meal acts synergistically at the level of the gastrointestinal tract (GIT) and blood system, for keeping the redox homeostasis in our organism and better balancing human health.

Photoisomerization Neutralizes Vasoconstrictive Activity of a Heme Degradation Product.

Delayed cerebral ischemia (DCI) caused by cerebral vasospasm is the leading determinant of poor outcome and mortality in subarachnoid hemorrhage (SAH) patients, but current treatment options lack effective prevention and therapy. Two substance families of heme degradation products (HDPs), bilirubin oxidation end products (BOXes) and propentdyopents (PDPs), are elicitors of pathologic cerebral hypoperfusion after SAH. Z-configured HDPs can be photoconverted into the corresponding E-isomers. We hypothesize that photoconversion is a detoxification mechanism to prevent and treat DCI. We irradiated purified Z-BOXes and Z-PDPs with UV/Vis light and documented the Z–E photoconversion. E-BOX A slowly reisomerizes to the thermodynamically favored Z-configuration in protein-containing media. In contrast to vasoconstrictive Z-BOX A, E-BOX A does not cause vasoconstriction in cerebral arterioles in vitro and in vivo in wild-type mice. Our results enable a critical assessment of light-induced intrathecal photoconversion and suggest the use of phototherapy to prevent and cure HDP-mediated cerebral vasospasms.

Complete nitrogen removal via simultaneous nitrification and denitrification by a novel phosphate accumulating Thauera sp. strain SND5

Bacteria capable of simultaneous nitrification and denitrification (SND) and phosphate removal could eliminate the need for separate reactors to remove nutrients from wastewater and alleviate competition for carbon sources between different heterotrophs in wastewater treatment plants (WWTPs). Here we report a newly isolated Thauera sp. strain SND5, that removes nitrogen and phosphorus from wastewater via SND and denitrifying-phosphate accumulation, respectively, without accumulation of metabolic intermediates. Strain SND5 simultaneously removes ammonium, nitrite, and nitrate at an average rate of 2.85, 1.98, and 2.42 mg-N/L/h, respectively. Batch testing, detection of functional genes, nitrogenous gas detection and thermodynamic analysis suggested that nitrogen gas, with hydroxylamine produced as an intermediate, was the most likely end products of heterotrophic ammonium oxidation by strain SND5. The generated end products and intermediates suggest a novel nitrogen removal mechanism for heterotrophic ammonium oxidation in strain SND5 (NH4+→NH2OH→N2). Strain SND5 was also found to be a denitrifying phosphate-accumulating organism, capable of accumulating phosphate, producing and storing polyhydroxybutyrate (PHB) as an intracellular source of carbon while using nitrate/nitrite or oxygen as an electron acceptor during PHB catabolism. This study identifies a novel pathway by which simultaneous nitrogen and phosphorus removal occurs in WWTPs via a single microbe.

Foods with Potential Prooxidant and Antioxidant Effects Involved in Parkinson's Disease.

Oxidative stress plays a fundamental role in the pathogenesis of Parkinson's disease (PD). Oxidative stress appears to be responsible for the gradual dysfunction that manifests via numerous cellular pathways throughout PD progression. This review will describe the prooxidant effect of excessive consumption of processed food. Processed meat can affect health due to its high sodium content, advanced lipid oxidation end-products, cholesterol, and free fatty acids. During cooking, lipids can react with proteins to form advanced end-products of lipid oxidation. Excessive consumption of different types of carbohydrates is a risk factor for PD. The antioxidant effects of some foods in the regular diet provide an inconclusive interpretation of the environment's mechanisms with the modulation of oxidation stress-induced PD. Some antioxidant molecules are known whose primary mechanism is the neuroprotective effect. The melatonin mechanism consists of neutralizing reactive oxygen species (ROS) and inducing antioxidant enzyme's expression and activity. N-acetylcysteine protects against the development of PD by restoring levels of brain glutathione. The balanced administration of vitamin B3, ascorbic acid, vitamin D and the intake of caffeine every day seem beneficial for brain health in PD. Excessive chocolate intake could have adverse effects in PD patients. The findings reported to date do not provide clear benefits for a possible efficient therapeutic intervention by consuming the nutrients that are consumed regularly.

P1021MARKERS OF “METABOLIC MEMORY” AND KIDNEY GRAFT FUNCTION IN PATIENTS WITH TYPE 1 DIABETES MELLITUS AFTER SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANTATION

Abstract Background and Aims To evaluate the relationship between oxidative stress markers and advanced glycation end products receptor (RAGE) with kidney graft function and complications of end-stage renal disease (ESRD) in patients with type 1 diabetes mellitus (T1DM), who reached stable euglycemia after simultaneous pancreas-kidney transplantation (SPKT). Method The study included 27 patients with T1DM duration for 21 [19; 28] years, diabetic nephropathy (DN) duration 7,0 [5,5; 13,5] years and duration of renal replacement therapy (dialysis) for 2 [1; 4] years after successful SPKT. The posttransplantation period at the time of inclusion was 61 [20; 90] months. Assessment included examination of oxidative stress markers (3-nitrothyrosine (3-NT), superoxide dismutase (SOD) and RAGE, analysis of the main kidney transplant dysfunction markers (KIM-1, NGAL, podocin, IL-18) and state of carbohydrate metabolism with monitoring for 1 year. All patients received three-component immunosuppressive therapy. Results SPKT allowed to achieve stable euglycemia (HbA1c 5.5 [5.1; 5.9] %, 5.5 [5.3; 5.7] % and С-peptide 2,9 [2,1; 3,6] ng/ml, 2,6 [2,0; 3,4] ng/ml at baseline and after 1 year of follow – up, respectively) and the restoration of graft function to the rate of estimated glomerular filtration rate (eGFR) CKD-EPI stage C2, albuminuria stage A1 of chronic kidney disease (CKD). However, 22% of patients experienced an increase of albumin-to-creatinine ratio to A2 at different times after surgical treatment. There was a statistically significant increase in SOD level (p=0.0005) and RAGE level (p=0.011) after 12 months of observation. Significant correlations of kidney transplant function parameters with “metabolic memory" markers (oxidative stress and RAGE) were also found: RAGE &amp; creatinine (R=0.50, p=0.02), RAGE &amp; KIM-1 (R=0.43, p=0.047), 3-NT&amp; eGFR (R= - 0.40, p=0.046), IL-18 &amp; SOD baseline (R=0.43, p=0.047). Attention is drawn to the correlations of RAGE &amp; HbA1c+12 month (R=0.47, p=0.01), podocin with HbA1c (R=-0.46, p=0.03), which may probably reflect the direct influence of carbohydrate metabolism compensation to the kidney graft condition and also the correlation of SOD baseline &amp; RAGE +12 month (R= - 0.70, p=0.0008), which may demonstrate the relative influence of components of "metabolic memory”. Conclusion SPKT as the way to achieve compensation of carbohydrate metabolism remains just one of factors of stable kidney graft function. The results of analysis of “metabolic memory” markers could indicate not only their direct contribution to the persistence of metabolic consequences of DM and DN, but also their possible participation in the development of recurrent nephropathy.

Methylxanthines Inhibit Primary Amine Oxidase and Monoamine Oxidase Activities of Human Adipose Tissue.

Background: Methylxanthines including caffeine and theobromine are widely consumed compounds and were recently shown to interact with bovine copper-containing amine oxidase. To the best of our knowledge, no direct demonstration of any interplay between these phytochemicals and human primary amine oxidase (PrAO) has been reported to date. We took advantage of the coexistence of PrAO and monoamine oxidase (MAO) activities in human subcutaneous adipose tissue (hScAT) to test the interaction between several methylxanthines and these enzymes, which are involved in many key pathophysiological processes. Methods: Benzylamine, methylamine, and tyramine were used as substrates for PrAO and MAO in homogenates of subcutaneous adipose depots obtained from overweight women undergoing plastic surgery. Methylxanthines were tested as substrates or inhibitors by fluorimetric determination of hydrogen peroxide, an end-product of amine oxidation. Results: Semicarbazide-sensitive PrAO activity was inhibited by theobromine, caffeine, and isobutylmethylxanthine (IBMX) while theophylline, paraxanthine, and 7-methylxanthine had little effect. Theobromine inhibited PrAO activity by 54% at 2.5 mM. Overall, the relationship between methylxanthine structure and the degree of inhibition was similar to that seen with bovine PrAO, although higher concentrations (mM) were required for inhibition. Theobromine also inhibited oxidation of tyramine by MAO, at the limits of its solubility in a DMSO vehicle. At doses higher than 12 % v/v, DMSO impaired MAO activity. MAO was also inhibited by millimolar doses of IBMX, caffeine and by other methylxanthines to a lesser extent. Conclusions: This preclinical study extrapolates previous findings with bovine PrAO to human tissues. Given that PrAO is a potential target for anti-inflammatory drugs, it indicates that alongside phosphodiesterase inhibition and adenosine receptor antagonism, PrAO and MAO inhibition could contribute to the health benefits of methylxanthines, especially their anti-inflammatory effects.