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1.
Kinetic and stoichiometric constraints determine the pathway of H2O2 consumption by red blood cells.
Orrico, F, Möller, MN, Cassina, A, Denicola, A, Thomson, L
Free radical biology & medicine. 2018;:231-239
Abstract
Red blood cells (RBC) are considered as a circulating sink of H2O2, but a significant debate remains over the role of the different intraerythocyte peroxidases. Herein we examined the kinetic of decomposition of exogenous H2O2 by human RBC at different cell densities, using fluorescent and oxymetric methods, contrasting the results against a mathematical model. Fluorescent measurements as well as oxygen production experiments showed that catalase was responsible for most of the decomposition of H2O2 at cell densities suitable for both experimental settings (0.1-10 × 1010 cell L-1), since sodium azide but not N-ethylmaleimide (NEM) inhibited H2O2 consumption. Oxygen production decreased at high cell densities until none was detected above 1.1 × 1012 cell L-1, being recovered after inhibition of the thiol dependent systems by NEM. This result underlined that the consumption of H2O2 by catalase prevail at RBC densities regularly used for research, while the thiol dependent systems predominate when the cell density increases, approaching the normal number in blood (5 × 1012 cell L-1). The mathematical model successfully reproduced experimental results and at low cell number it showed a time sequence involving Prx as the first line of defense, followed by catalase, with a minor role by Gpx. The turning points were given by the total consumption of reduced Prx in first place and reduced GSH after that. However, Prx alone was able to account for the added H2O2 (50 µM) at physiological RBC density, calling attention to the importance of cell density in defining the pathway of H2O2 consumption and offering an explanation to current apparently conflicting results in the literature.
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2.
The role of operating parameters and oxidative damage mechanisms of advanced chemical oxidation processes in the combat against antibiotic-resistant bacteria and resistance genes present in urban wastewater.
Michael-Kordatou, I, Karaolia, P, Fatta-Kassinos, D
Water research. 2018;:208-230
Abstract
An upsurge in the study of antibiotic resistance in the environment has been observed in the last decade. Nowadays, it is becoming increasingly clear that urban wastewater is a key source of antibiotic resistance determinants, i.e. antibiotic-resistant bacteria and antibiotic resistance genes (ARB&ARGs). Urban wastewater reuse has arisen as an important component of water resources management in the European Union and worldwide to address prolonged water scarcity issues. Especially, biological wastewater treatment processes (i.e. conventional activated sludge), which are widely applied in urban wastewater treatment plants, have been shown to provide an ideal environment for the evolution and spread of antibiotic resistance. The ability of advanced chemical oxidation processes (AOPs), e.g. light-driven oxidation in the presence of H2O2, ozonation, homogeneous and heterogeneous photocatalysis, to inactivate ARB and remove ARGs in wastewater effluents has not been yet evaluated through a systematic and integrated approach. Consequently, this review seeks to provide an extensive and critical appraisal on the assessment of the efficiency of these processes in inactivating ARB and removing ARGs in wastewater effluents, based on recent available scientific literature. It tries to elucidate how the key operating conditions may affect the process efficiency, while pinpointing potential areas for further research and major knowledge gaps which need to be addressed. Also, this review aims at shedding light on the main oxidative damage pathways involved in the inactivation of ARB and removal of ARGs by these processes. In general, the lack and/or heterogeneity of the available scientific data, as well as the different methodological approaches applied in the various studies, make difficult the accurate evaluation of the efficiency of the processes applied. Besides the operating conditions, the variable behavior observed by the various examined genetic constituents of the microbial community, may be directed by the process distinct oxidative damage mechanisms in place during the application of each treatment technology. For example, it was shown in various studies that the majority of cellular damage by advanced chemical oxidation may be on cell wall and membrane structures of the targeted bacteria, leaving the internal components of the cells relatively intact/able to repair damage. As a result, further in-depth mechanistic studies are required, to establish the optimum operating conditions under which oxidative mechanisms target internal cell components such as genetic material and ribosomal structures more intensively, thus conferring permanent damage and/or death and preventing potential post-treatment re-growth.
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3.
Is maternal microbial metabolism an early-life determinant of health?
Romano, KA, Rey, FE
Lab animal. 2018;(9):239-243
Abstract
Mounting evidence suggests that environmental stress experienced in utero (for example, maternal nutritional deficits) establishes a predisposition in the newborn to the development of chronic diseases later in life. This concept is often referred to as the "fetal origins hypothesis" or "developmental origins of health and disease". Since its first proposal, epigenetics has emerged as an underlying mechanism explaining how environmental cues become gestationally "encoded". Many of the enzymes that impart and maintain epigenetic modifications are highly sensitive to nutrient availability, which can be influenced by the metabolic activities of the intestinal microbiota. Therefore, the maternal microbiome has the potential to influence epigenetics in utero and modulate offspring's long-term health trajectories. Here we summarize the current understanding of the interactions that occur between the maternal gut microbiome and the essential nutrient choline, that is not only required for fetal development and epigenetic regulation but is also a growth substrate for some microbes. Bacteria able to metabolize choline benefit from the presence of this nutrient and compete with the host for its access, which under extreme conditions may elicit signatures of choline deficiency. Another consequence of bacterial choline metabolism is the accumulation of the pro-inflammatory, pro-thrombotic metabolite trimethylamine-N-oxide (TMAO). Finally, we discuss how these different facets of microbial choline metabolism may influence infant development and health trajectories via epigenetic mechanisms and more broadly place a call to action to better understand how maternal microbial metabolism can shape their offspring's propensity to chronic disease development later in life.
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4.
Exposure of Microcystis aeruginosa to hydrogen peroxide and titanium dioxide under visible light conditions: Modeling the impact of hydrogen peroxide and hydroxyl radical on cell rupture and microcystin degradation.
Chang, CW, Huo, X, Lin, TF
Water research. 2018;:217-226
Abstract
The aims of this study are to evaluate, under visible light conditions, the ability of H2O2 and TiO2 to produce OH, their quantitative impacts on the cell integrity of Microcystis, and the subsequent release and degradation of microcystins (MCs). A sequential reaction model was developed, including one sub-model to simulate the rupture kinetics for cell integrity of Microcystis, and another to describe the release and degradation of MCs. For cell rupture, the dual-oxidant Delayed Chick-Watson model (DCWM) and dual-oxidant Hom model (HM) were first proposed and developed, giving excellent simulation results of cell rupture kinetics. Kinetic rate constants between Microcystis cells and H2O2 [Formula: see text] as well as OH (k•OH, Cell) under visible light successfully separated the individual effects of H2O2 and OH on Microcystis. The dual-oxidant models were further validated with additional experiments, making the models more convincing. Finally, the dual-oxidant cell rupture models were integrated with the MC degradation model and well predicted the observed MCs concentrations in the experimental systems. The results of this study not only demonstrate the potential application of H2O2 and TiO2 for the control of cyanobacteria and metabolites in natural water bodies, but also provide a new methodology to differentiate the individual contributions of the two oxidants, H2O2 and OH, on cell rupture, thus giving a novel way to more precisely determine the effective doses of applied oxidants for cyanobacteria control.
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5.
Carvacrol ameliorates haematological parameters, oxidant/antioxidant biomarkers and pulmonary function tests in patients with sulphur mustard-induced lung disorders: A randomized double-blind clinical trial.
Khazdair, MR, Alavinezhad, A, Boskabady, MH
Journal of clinical pharmacy and therapeutics. 2018;(5):664-674
Abstract
WHAT IS KNOWN AND OBJECTIVE In this study, the effect of carvacrol (CAR) on pulmonary function tests (PFT), haematological indices and oxidant/antioxidant biomarkers in patients with sulphur mustard (SM)-induced lung disorders was examined. METHODS Twenty patients exposed to SM 27-30 years ago were divided into two groups and treated with either placebo (P) or CAR (1.2 mg/kg per day) (n = 10 for each group). Forced vital capacity (FVC), peak expiratory flow (PEF), total and different white blood cell (WBC), haematological parameters and oxidant/antioxidant biomarkers were measured at the baseline (step 0), one and two months (steps I and II, respectively) after starting the treatment. RESULTS AND DISCUSSION PEF was significantly increased in the CAR-treated group in step II compared to step 0 (P < .01). Total WBC (P < .01) and neutrophil (P < .05) count in the CAR-treated group were significantly decreased in the group in steps I and II (P < .01 for both cases) compared to step 0. The levels of thiol, superoxide dismutase and catalase in the CAR-treated group were significantly increased (P < .05 to P < .001) in steps I and II, but malondialdehyde significantly decreased in step II compared to step 0 (P < .01). The percentage of total and differential WBC, oxidant/antioxidant biomarkers, FVC and PEF values following a two-month treatment period were significantly improved in the CAR-treated group compared to the placebo group (P < .05 to P < .001). WHAT IS NEW AND CONCLUSION Two-month treatment with CAR reduced inflammatory cells and oxidant biomarkers, whereas increased antioxidant biomarkers and improved PFT tests in SM-exposed patients.
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6.
Influence of exogenous lactoferrin on the oxidant/antioxidant balance and molecular profile of hormone receptor-positive and -negative human breast cancer cells in vitro.
Zalutskii, IV, Lukianova, NY, Storchai, DM, Burlaka, AP, Shvets, YV, Borikun, TV, Todor, IM, Lukashevich, VS, Rudnichenko, YA, Chekhun, VF
Experimental oncology. 2017;(2):106-111
Abstract
AIM: To investigate the mechanisms of cytotoxic activity and pro-/antioxidant effect of lactoferrin on hormone receptor-positive and receptor-negative breast cancer cells in vitro. MATERIALS AND METHODS The study was performed on receptor-positive (MCF-7, T47D) and receptor-negative (MDA-MB-231, MDA-MB-468) human breast cancer cell lines. Immunocytochemical staining, flow cytometry, low-temperature electron paramagnetic resonance, and the Comet assay were used. RESULTS Upon treatment with lactoferrin, the increased levels of reactive oxygen species (ROS) (p < 0.05), NO generation rate by inducible NO-synthase (p < 0.05) and the level of "free" iron (p < 0.05) were observed. Moreover, the effects of lactoferrin were more pronounced in receptor-negative MDA-MB-231 and MDA-MB-468 cells. These changes resulted in increased expression of proapoptotic Bax protein (p < 0.05), reduced expression of the antiapoptotic Bcl-2 protein (p < 0.05) and level of not-oxidized mitochondrial cardiolipin (1.4-1.7-fold, p < 0.05). This, in turn, caused an increase in the percentage of apoptotic cells (by 14-24%, p < 0.05). Cytotoxic effects of lactoferrin were accompanied by an increase in the percentage of DNA in the comet tail and blocking cell cycle at G2/M phase, especially in receptor-negative cell lines. CONCLUSION The study showed that exogenous lactoferrin causes a violation of an antioxidant balance by increasing the level of ROS, "free" iron and NO generation rate, resalting in the blocking of cell cycle at G2/M-phase and apoptosis of malignant cells.
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7.
Differentiation impairs Bach1 dependent HO-1 activation and increases sensitivity to oxidative stress in SH-SY5Y neuroblastoma cells.
Piras, S, Furfaro, AL, Brondolo, L, Passalacqua, M, Marinari, UM, Pronzato, MA, Nitti, M
Scientific reports. 2017;(1):7568
Abstract
Neuronal adaptation to oxidative stress is crucially important in order to prevent degenerative diseases. The role played by the Nrf2/HO-1 system in favoring cell survival of neuroblastoma (NB) cells exposed to hydrogen peroxide (H2O2) has been investigated using undifferentiated or all-trans retinoic acid (ATRA) differentiated SH-SY5Y cells. While undifferentiated cells were basically resistant to the oxidative stimulus, ATRA treatment progressively decreased cell viability in response to H2O2. HO-1 silencing decreased undifferentiated cell viability when exposed to H2O2, proving the role of HO-1 in cell survival. Conversely, ATRA differentiated cells exposed to H2O2 showed a significantly lower induction of HO-1, and only the supplementation with low doses of bilirubin (0,5-1 μM) restored viability. Moreover, the nuclear level of Bach1, repressor of HO-1 transcription, strongly decreased in undifferentiated cells exposed to oxidative stress, while did not change in ATRA differentiated cells. Furthermore, Bach1 was displaced from HO-1 promoter in undifferentiated cells exposed to H2O2, enabling the binding of Nrf2. On the contrary, in ATRA differentiated cells treated with H2O2, Bach1 displacement was impaired, preventing Nrf2 binding and limiting HO-1 transcription. In conclusion, our findings highlight the central role of Bach1 in HO-1-dependent neuronal response to oxidative stress.
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8.
Dioxygen activation by nonheme iron enzymes with the 2-His-1-carboxylate facial triad that generate high-valent oxoiron oxidants.
Kal, S, Que, L
Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry. 2017;(2-3):339-365
Abstract
The 2-His-1-carboxylate facial triad is a widely used scaffold to bind the iron center in mononuclear nonheme iron enzymes for activating dioxygen in a variety of oxidative transformations of metabolic significance. Since the 1990s, over a hundred different iron enzymes have been identified to use this platform. This structural motif consists of two histidines and the side chain carboxylate of an aspartate or a glutamate arranged in a facial array that binds iron(II) at the active site. This triad occupies one face of an iron-centered octahedron and makes the opposite face available for the coordination of O2 and, in many cases, substrate, allowing the tailoring of the iron-dioxygen chemistry to carry out a plethora of diverse reactions. Activated dioxygen-derived species involved in the enzyme mechanisms include iron(III)-superoxo, iron(III)-peroxo, and high-valent iron(IV)-oxo intermediates. In this article, we highlight the major crystallographic, spectroscopic, and mechanistic advances of the past 20 years that have significantly enhanced our understanding of the mechanisms of O2 activation and the key roles played by iron-based oxidants.
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9.
The value of serum pro-oxidant/antioxidant balance in the assessment of asphyxia in term neonates.
Boskabadi, H, Zakerihamidi, M, Heidarzadeh, M, Avan, A, Ghayour-Mobarhan, M, Ferns, GA
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2017;(13):1556-1561
Abstract
OBJECTIVE Asphyxia is a major cause of disabilities in term-born infants. Here we have explored the value in HIE (hypoxic-ischemic-encephalopathy) of using a combination of serum pro-oxidant/antioxidant balance (PAB) assay for predicting the prognosis of asphyxia. METHOD Ninety term neonates with asphyxia were enrolled and followed up for two years. Serum PAB, demographic/biochemical characteristics of mothers, and their neonates were determined. The Denver II test was used to assess outcomes. RESULTS Of the 90 asphyxiated neonates, 47 (52.2%) had a normal outcome and 43 babies (47.8%) had abnormal outcome. Serum PAB levels in neonates with normal and abnormal outcomes were 17.1 ± 9.23 and 48.27 ± 41.30 HK, respectively. A combination of HIE intensity and PAB, compared to other indicators, had a higher predictive-value (95.2%) for outcomes in asphyxiated babies. CONCLUSION We demonstrate that PAB in combination with HIE grade may have a better predictive value for the prognosis of asphyxiated babies and predicting future neurologic problems in asphyxiated term infants.
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10.
Increased oxidative stress parameters in children with moderate iodine deficiency.
Kurku, H, Gencer, A, Pirgon, O, Buyukinan, M, Aslan, N
Journal of pediatric endocrinology & metabolism : JPEM. 2016;(10):1159-1164
Abstract
BACKGROUND Iodine is a part of thyroid hormones and has been reported to act directly as an antioxidant or induce indirectly antioxidant enzymes. This study aimed to assess the urinary iodine concentration and its relationship between the antioxidant and oxidative stress capacity in healthy school-aged children. METHODS In total, 196 students from five primary schools, randomly selected between 9 and 12 years (mean age: 10.2±1.2 years), were enrolled in the study. Urinary iodine levels were measured by spectrophotometry with the Sandell-Kolthoff reaction. Total antioxidant status (TAS) and total oxidant status (TOS) were analysed from urine samples. The ratio of TOS to TAS was regarded as an oxidative stress index (OSI), an indicator of the degree of oxidative status. RESULTS Fifty-four percentage (107) of the children had iodine deficiency (ID) and the majority of them (30%) had mild ID. There was no severe-ID child in the population (<20 μg/L). Urine TAS levels were significantly lower in the moderate-ID group than in the mild-ID group (6.5±4.1 vs. 11.3±4.1 mmol, p<0.001) and the iodine-sufficient group (11.0±5.3 μmol, p<0.001). TOS levels and OSI were found higher in the moderate-ID group than in the mild-ID group (4.8±2.1 vs. 3.7±2.1 μmol, p<0.001) and the iodine-sufficient group (4.8±2.1 vs. 3.4±2.5 mmol, p<0.001). In the moderate-ID group, low urine iodine levels exhibited significant negative correlations with OSI (r=-0.660) and TOS (r=-0.248) and a positive correlation with TAS (r=0.475). CONCLUSIONS We found that children with moderate ID were exposed to more oxidative burden than children with mild ID or iodine sufficiency. Increased systemic oxidative stress induced by moderate ID could cause development of ID-related complications and diseases. Iodine supplementation could have a beneficial role in the prevention of oxidative stress.