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1.
Complex Interplay of Heme-Copper Oxidases with Nitrite and Nitric Oxide.
Chen, J, Xie, P, Huang, Y, Gao, H
International journal of molecular sciences. 2022;(2)
Abstract
Nitrite and nitric oxide (NO), two active and critical nitrogen oxides linking nitrate to dinitrogen gas in the broad nitrogen biogeochemical cycle, are capable of interacting with redox-sensitive proteins. The interactions of both with heme-copper oxidases (HCOs) serve as the foundation not only for the enzymatic interconversion of nitrogen oxides but also for the inhibitory activity. From extensive studies, we now know that NO interacts with HCOs in a rapid and reversible manner, either competing with oxygen or not. During interconversion, a partially reduced heme/copper center reduces the nitrite ion, producing NO with the heme serving as the reductant and the cupric ion providing a Lewis acid interaction with nitrite. The interaction may lead to the formation of either a relatively stable nitrosyl-derivative of the enzyme reduced or a more labile nitrite-derivative of the enzyme oxidized through two different pathways, resulting in enzyme inhibition. Although nitrite and NO show similar biochemical properties, a growing body of evidence suggests that they are largely treated as distinct molecules by bacterial cells. NO seemingly interacts with all hemoproteins indiscriminately, whereas nitrite shows high specificity to HCOs. Moreover, as biologically active molecules and signal molecules, nitrite and NO directly affect the activity of different enzymes and are perceived by completely different sensing systems, respectively, through which they are linked to different biological processes. Further attempts to reconcile this apparent contradiction could open up possible avenues for the application of these nitrogen oxides in a variety of fields, the pharmaceutical industry in particular.
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2.
Acceptability and Feasibility of a 13-Week Pilot Randomised Controlled Trial Testing the Effects of Incremental Doses of Beetroot Juice in Overweight and Obese Older Adults.
Babateen, AM, Shannon, OM, O'Brien, GM, Okello, E, Khan, AA, Rubele, S, Wightman, E, Smith, E, McMahon, N, Olgacer, D, et al
Nutrients. 2021;(3)
Abstract
Nitrate-rich food can increase nitric oxide production and improve vascular and brain functions. This study examines the feasibility of a randomised controlled trial (RCT) testing the effects of prolonged consumption of different doses of dietary nitrate (NO3-) in the form of beetroot juice (BJ) in overweight and obese older participants. A single-blind, four-arm parallel pilot RCT was conducted in 62 overweight and obese (30.4 ± 4 kg/m2) older participants (mean ± standard deviation (SD), 66 ± 4 years). Participants were randomized to: (1) high-NO3- (HN: 2 × 70 mL BJ/day) (2) medium-NO3- (MN: 70 mL BJ/day), (3) low-NO3- (LN: 70 mL BJ on alternate days) or (4) Placebo (PL: 70 mL of NO3--depleted BJ on alternate days), for 13 weeks. Compliance was checked by a daily log of consumed BJ, NO3- intake, and by measuring NO3- and NO2- concentrations in plasma, saliva, and urine samples. Fifty participants completed the study. Self-reported compliance to the interventions was >90%. There were significant positive linear relationships between NO3- dose and the increase in plasma and urinary NO3- concentration (R2 = 0.71, P < 0.001 and R2 = 0.46 P < 0.001, respectively), but relationships between NO3- dose and changes in salivary NO3- and NO2- were non-linear (R2 = 0.35, P = 0.002 and R2 = 0.23, P = 0.007, respectively). The results confirm the feasibility of prolonged BJ supplementation in older overweight and obese adults.
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3.
Diagnostic Accuracy of Point-of-care Nitrite and Leukocyte Esterase Dipstick Test for the Screening of Pediatric Urinary Tract Infections.
Suresh, J, Krishnamurthy, S, Mandal, J, Mondal, N, Sivamurukan, P
Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia. 2021;(3):703-710
Abstract
Our study aimed to evaluate the diagnostic performance of point-of-care nitrite and leukocyte esterase (LE) dipsticks in the diagnosis of suspected urinary tract infection (UTI) in infants <6 months (young infants) versus older children. The secondary objectives were to study the dipstick efficacy in children with congenital anomalies of the kidney and urinary tract (CAKUT) versus those without CAKUT; in children with simple UTI versus complicated UTI; and to evaluate the clinico-microbiological profile of children presenting with UTI. In this prospective observational study, cases with suspected UTI were enrolled from pediatric emergency or outpatient departments. Urine was collected for performing the urine dipstick and culture. Descriptive data regarding CAKUT, age, gender, etc., were recorded in a predesigned pro forma. We screened 506 children with suspected UTI, of whom 221 had urine culture positive. Approximately 38.4% of the children with UTI had underlying CAKUT, while 7.6% had renal scars. The most common CAKUT was vesicoureteric reflux (VUR). About 12 patients (2.3%) were known to have CAKUT at the time of enrollment in the study. In infants <6 months, LE dipstick had sensitivity 92%, specificity 89.7%, positive predictive value (PPV) 86.7%, negative predictive value (NPV) 93.8%, likelihood ratio (LR) + 8.9, LR- 0.09. In infants <6 months, nitrite dipstick had sensitivity 38%, specificity 97%, PPV 90.4%, NPV 68%, LR+ 12.6 and LR-0.63. In the age group 6 months to 12 years, the efficacy was better for both dipsticks. In age group more than 6 months to 12 years, LE dipstick had sensitivity 96.4%, specificity 95.8%, PPV 94.8 %, NPV 97.2%, LR+ 22.9, LR- 0.04. In age group more than six months to 12 years, nitrite dipstick had sensitivity 94.7%, specificity 99.5%, PPV 99.3%, NPV 96%, LR+ 189.4, and LR-0.05.
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4.
Replacement of Nitrite in Meat Products by Natural Bioactive Compounds Results in Reduced Exposure to N-Nitroso Compounds: The PHYTOME Project.
van Breda, SG, Mathijs, K, Pieters, HJ, Sági-Kiss, V, Kuhnle, GG, Georgiadis, P, Saccani, G, Parolari, G, Virgili, R, Sinha, R, et al
Molecular nutrition & food research. 2021;(20):e2001214
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Abstract
SCOPE It has been proposed that endogenously form N-nitroso compounds (NOCs) are partly responsible for the link between red meat consumption and colorectal cancer (CRC) risk. As nitrite has been indicated as critical factor in the formation of NOCs, the impact of replacing the additive sodium nitrite (E250) by botanical extracts in the PHYTOME project is evaluated. METHOD AND RESULTS A human dietary intervention study is conducted in which healthy subjects consume 300 g of meat for 2 weeks, in subsequent order: conventional processed red meat, white meat, and processed red meat with standard or reduced levels of nitrite and added phytochemicals. Consumption of red meat products enriched with phytochemicals leads to a significant reduction in the faecal excretion of NOCs, as compared to traditionally processed red meat products. Gene expression changes identify cell proliferation as main affects molecular mechanism. High nitrate levels in drinking water in combination with processed red meat intake further stimulates NOC formation, an effect that could be mitigated by replacement of E250 by natural plant extracts. CONCLUSION These findings suggest that addition of natural extracts to conventionally processed red meat products may help to reduce CRC risk, which is mechanistically support by gene expression analyses.
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Nitrate- and Nitrite-Sensing Histidine Kinases: Function, Structure, and Natural Diversity.
Gushchin, I, Aleksenko, VA, Orekhov, P, Goncharov, IM, Nazarenko, VV, Semenov, O, Remeeva, A, Gordeliy, V
International journal of molecular sciences. 2021;(11)
Abstract
Under anaerobic conditions, bacteria may utilize nitrates and nitrites as electron acceptors. Sensitivity to nitrous compounds is achieved via several mechanisms, some of which rely on sensor histidine kinases (HKs). The best studied nitrate- and nitrite-sensing HKs (NSHKs) are NarQ and NarX from Escherichia coli. Here, we review the function of NSHKs, analyze their natural diversity, and describe the available structural information. In particular, we show that around 6000 different NSHK sequences forming several distinct clusters may now be found in genomic databases, comprising mostly the genes from Beta- and Gammaproteobacteria as well as from Bacteroidetes and Chloroflexi, including those from anaerobic ammonia oxidation (annamox) communities. We show that the architecture of NSHKs is mostly conserved, although proteins from Bacteroidetes lack the HAMP and GAF-like domains yet sometimes have PAS. We reconcile the variation of NSHK sequences with atomistic models and pinpoint the structural elements important for signal transduction from the sensor domain to the catalytic module over the transmembrane and cytoplasmic regions spanning more than 200 Å.
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Marching to the Beet: The effect of dietary nitrate supplementation on high altitude exercise performance and adaptation during a military trekking expedition.
Marshall, AR, Rimmer, JE, Shah, N, Bye, K, Kipps, C, Woods, DR, O'Hara, J, Boos, CJ, Barlow, M
Nitric oxide : biology and chemistry. 2021;:70-77
Abstract
PURPOSE The aim was to investigate the effect of dietary nitrate supplementation (in the form of beetroot juice, BRJ) for 20 days on salivary nitrite (a potential precursor of bioactive nitric oxide), exercise performance and high altitude (HA) acclimatisation in field conditions (hypobaric hypoxia). METHODS This was a single-blinded randomised control study of 22 healthy adult participants (12 men, 10 women, mean age 28 ± 12 years) across a HA military expedition. Participants were randomised pre-ascent to receive two 70 ml dose per day of either BRJ (~12.5 mmol nitrate per day; n = 11) or non-nitrate calorie matched control (n = 11). Participants ingested supplement doses daily, beginning 3 days prior to departure and continued until the highest sleeping altitude (4800 m) reached on day 17 of the expedition. Data were collected at baseline (44 m altitude), at 2350 m (day 9), 3400 m (day 12) and 4800 m (day 17). RESULTS BRJ enhanced the salivary levels of nitrite (p = 0.007). There was a significant decrease in peripheral oxygen saturation and there were increases in heart rate, diastolic blood pressure, and rating of perceived exertion with increasing altitude (p=<0.001). Harvard Step Test fitness scores significantly declined at 4800 m in the control group (p = 0.003) compared with baseline. In contrast, there was no decline in fitness scores at 4800 m compared with baseline (p = 0.26) in the BRJ group. Heart rate recovery speed following exercise at 4800 m was significantly prolonged in the control group (p=<0.01) but was unchanged in the BRJ group (p = 0.61). BRJ did not affect the burden of HA illness (p = 1.00). CONCLUSIONS BRJ increases salivary nitrite levels and ameliorates the decline in fitness at altitude but does not affect the occurrence of HA illness.
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Oxidative stress and nitrate/nitrite (NOx) status following citrulline supplementation in type 2 diabetes: a randomised, double-blind, placebo-controlled trial.
Azizi, S, Ebrahimi-Mameghani, M, Mobasseri, M, Karamzad, N, Mahdavi, R
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2021;(1):64-72
Abstract
BACKGROUND The pathogenesis of diabetes is accompanied by oxidative stress. Citrulline can be considered as a potent antioxidant. The present study aimed to examine the effects of citrulline supplementation on the status of oxidative stress and serum levels of nitrite/nitrate (NOx) in patients suffering from type 2 diabetes (T2DM). METHODS The present study comprises a double-blind placebo-controlled randomised clinical trial. The study subjects include 54 patients with T2DM chosen from specialised clinics of Tabriz University of Medical Sciences. The patients were allocated to one of the placebo or intervention groups. The patients in the placebo and the intervention group received one sachet of microcrystalline cellulose or l-citrulline (3 g), respectively, every day for 2 months. Malondialdehyde (MDA), glutathione peroxidase (GPx), total antioxidant capacity (TAC), superoxide dismutase (SOD), serum levels of fasting blood sugar (FBS), citrulline and NOx were assessed before and after the intervention. RESULTS Forty-five patients completed the trial. Significant decreases were found in serum levels of FBS and MDA. Serum levels of TAC, citrulline and NOx in the intervention group increased compared to those of the placebo group, after adjusting the data for the baseline values and confounders. Differences between and within the two groups were statistically nonsignificant for GPx and SOD at the end of the study. Body mass index and energy intake were not changed significantly after the intervention. CONCLUSIONS The results of the present study show the positive effects of citrulline supplementation with respect to attenuating FBS levels and oxidative stress, as well as boosting NOx status, in patients with T2DM.
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A novel electrochemical sensor based on ion imprinted polymer and gold nanomaterials for nitrite ion analysis in exhaled breath condensate.
Diouf, A, El Bari, N, Bouchikhi, B
Talanta. 2020;:120577
Abstract
Human Exhaled Breath Condensate (EBC) contains markers of several inflammatory diseases. Its analysis is of interest to a number of researchers. Nitrite ions (NO2-), which are widely used in our daily lives, are nevertheless among these indicators. In this study, a simple, fast, portable, non-invasive and cheap electrochemical sensor is developed for the analysis of the nitrite profile in EBC. In this regard, sodium nitrite (NaNO2) was first immobilized on self-assembled 2-aminothiophenol (2-ATP) on a screen-printed gold electrode (Au-SPE). Then, a polymer matrix composed of polyvinyl alcohol (PVA) crosslinked with glutaraldehyde (GA) was combined with gold nanoparticles (Au-NPs) to cover the modified Au-SPE and complete the fabrication of the Ion Imprinted Polymer (IIP) sensor. The electrochemical behaviour of the sensor was monitored using Cyclic Voltammetry (CV), Electrochemical Impedance Spectroscopy (EIS) and Differential Pulse Voltammetry (DPV) methods, while the morphology and chemical composition of its layers were observed by infrared Fourier transform (FTIR), Atomic Force Microscopy (AFM) and Scanning Electron Microscopy coupled with energy dispersion X-Ray spectroscopy (SEM-EDS) techniques. In addition, after a successful control test using a Non-Imprinted Ion Polymer (NIIP) sensor, the obtained results demonstrated satisfactory sensitivity and selectivity to nitrite compared to co-existing interfering substances in EBC, such as nitrate, acetate and ammonium nitrate. Under improved experimental conditions, the nitrite IIP sensor exhibits responses proportional to nitrite concentrations (R2 = 0.96) over a concentration range of 0.5-50 μg mL-1 with a detection limit (LOD) of 4 μmol L-1 (signal-to-noise ratio S/N = 3). The proposed approach was well applied for the nitrite determination in EBC samples with a relative standard deviation (RSD = 4%) and could open clinical applications in respiratory medicine.
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Geochemical and isotopic study of abiotic nitrite reduction coupled to biologically produced Fe(II) oxidation in marine environments.
Benaiges-Fernandez, R, Offeddu, FG, Margalef-Marti, R, Palau, J, Urmeneta, J, Carrey, R, Otero, N, Cama, J
Chemosphere. 2020;:127554
Abstract
Estuarine sediments are often characterized by abundant iron oxides, organic matter, and anthropogenic nitrogen compounds (e.g., nitrate and nitrite). Anoxic dissimilatory iron reducing bacteria (e.g., Shewanella loihica) are ubiquitous in these environments where they can catalyze the reduction of Fe(III) (oxyhydr)oxides, thereby releasing aqueous Fe(II). The biologically produced Fe(II) can later reduce nitrite to form nitrous oxide. The effect on nitrite reduction by both biologically produced and artificially amended Fe(II) was examined experimentally. Ferrihydrite was reduced by Shewanella loihica in a batch reaction with an anoxic synthetic sea water medium. Some of the Fe(II) released by S. loihica adsorbed onto ferrihydrite, which was involved in the transformation of ferrihydrite to magnetite. In a second set of experiments with identical medium, no microorganism was present, instead, Fe(II) was amended. The amount of solid-bound Fe(II) in the experiments with bioproduced Fe(II) increased the rate of abiotic NO2- reduction with respect to that with synthetic Fe(II), yielding half-lives of 0.07 and 0.47 d, respectively. The δ18O and δ15N of NO2- was measured through time for both the abiotic and innoculated experiments. The ratio of ε18O/ε15N was 0.6 for the abiotic experiments and 3.1 when NO2- was reduced by S. loihica, thus indicating two different mechanisms for the NO2- reduction. Notably, there is a wide range of the ε18O/ε15N values in the literature for abiotic and biotic NO2- reduction, as such, the use of this ratio to distinguish between reduction mechanisms in natural systems should be taken with caution. Therefore, we suggest an additional constraint to identify the mechanisms (i.e. abiotic/biotic) controlling NO2- reduction in natural settings through the correlation of δ15N-NO2- and the aqueous Fe(II) concentration.
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10.
Initial nitrite concentration promote nitrite-oxidizing bacteria activity recovery from transient anoxia: Experimental and modeling investigations.
Liu, W, Liu, C, Zhang, S, Gu, P, Shen, C, Wang, W, Peng, Y
Bioresource technology. 2019;:121711
Abstract
Transient anoxia due to the periodic anoxic/aerobic operation is beneficial for the nitrite-oxidizing bacteria (NOB) suppression. A continuous reactor of modified University of Cape Town process treating municipal wastewater was equipped with alternating anoxic/aerobic zones to maintain nitritation. Higher nitrite accumulation ratio in the oxic zones was achieved through transient anoxia and shorter aerobic actual hydraulic retention time (15 min), but it steeply deteriorated from above 95.0% to 21.0% after elevated temperature (25 °C). Batch experiments indicated that the existence of initial nitrite at the starting of aerobic phase promoted the recovery of NOB activity from transient anoxia and inhibited the activity of ammonium-oxidizing bacteria. Furthermore, a supplemental modeling further confirmed that the specific growth rates of NOB (μNOB) decreased at the anoxic phase and the recovery extent of μNOB after anoxic exposure have a positive correlation with the initial concentrations of nitrite, leading to the failure of maintaining nitritation.