Depletion Of Antioxidants Research Articles

Heavy Metal Toxicity and its Treatment

Abstract Heavy metals are ubiquitous environmental contaminants that are capable of inducing a broad range of physiological, biochemical and behavioural dysfunctions. Heavy metal poisoning remains a persistent public health problem in Malaysia and throughout the world. Exposure to toxic metals and compounds containing them through inhalation, ingestion or skin contact may cause various pathophysiological conditions, and the nervous system is the most susceptible organ system to this exposure causing a condition known as heavy metal-mediated neurotoxicity. This review summarises the current understanding of the mechanisms by which arsenic, lead and mercury induce heavy metal-mediated neurotoxicity. These heavy metals cause toxic manifestations in the nervous system primarily through the presence of excessive pro-oxidants and depletion of antioxidants, causing an imbalance homeostasis also described as oxidative stress. In addition, this article also reviews previous common chelation treatments and emerging antioxidant treatments since antioxidants have become the current interest in the prevention and treatment of these heavy metal-mediated toxicities.

Demyelination in cuprizone mice is ameliorated by calycosin mediated through astrocyte Nrf2 signaling pathway

Oxidative stress plays a pivotal role in multiple sclerosis (MS), triggering demyelination predominantly through excessive peroxide production and the depletion of antioxidants. The accumulation of oxidative damage can be caused by dysregulation of astrocytes, which are the brain's main regulators of oxidative homeostasis. Calycosin, an essential bioactive component extracted from Astragalus, is recognized for its neuroprotective properties. Although recent research has highlighted calycosin's neuroprotective capabilities, its role in demyelinating conditions like MS remains unclear. In this work, we examined the possible molecular mechanism of calycosin's neuroprotective effect on cuprizone (CPZ)-induced demylination in mice. According to our research, calycosin successfully reduced demyelination and behavioral dysfuction in CPZ mice. Calycosin also decreased the production of oxidative stress and enhanced the expression of antioxidants in CPZ mice and in astrocytes induced by hydrogen peroxide (H2O2). Furthermore, both in vivo and in vitro experiments demonstrated that calycosin promoted the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) along with the upregulation of heme oxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), and superoxide dismutase (SOD). Importantly, the application of all-trans retinoic acid (ATRA), a specific inhibitor of Nrf2, effectively reversed the myelin-protective and antioxidant effects conferred by calycosin. This study suggested that calycosin might exert neuroprotection by inhibiting oxidative stress and reducing demyelination via the activation of astrocyte Nrf2 signaling. These findings indicated that calycosin might be a potential candidate for treating MS.

Monosodium glutamate induces hypothalamic–pituitary–adrenal axis hyperactivation, glucocorticoid receptors down-regulation, and systemic inflammatory response in young male rats: Impact on miR-155 and miR-218

Abstract Young children are attracted to flavored foods with enhancers, particularly monosodium glutamate (MSG). Experimental studies have proven that MSG can alter the hypothalamic–pituitary–adrenal (HPA) axis response in neonates. We, therefore, investigated the modulation of microRNAs (miRNAs) by dietary MSG and its association with the stimulation of the HPA axis and inflammatory response in young male rats. One-month-old male rats were fed chow enriched with MSG (3 g/kg) for 16 weeks. Feeding MSG to rats markedly up-regulated hypothalamic miR-218, Toll-like receptors-4, and nuclear factor-kB but down-regulated miR-155 and glucocorticoid receptors (GR). In addition, it triggered a remarkable elevation in adrenocortical lipid peroxidation and depletion of antioxidants. These changes were coupled with increased plasma levels of the HPA axis hormones, comprising corticotropin-releasing hormone, adrenocorticotropic hormone, corticosterone levels, and serum pro-inflammatory cytokines. Taken together, current findings indicated that MSG caused an activation of the HPA axis, a down-regulation of GRs, and a systemic inflammatory response. These disturbances were associated with modulating hypothalamic miRNAs, encompassing miR-218 and 155.

Chemical speciation and oxidative potential of PM10 in different residential microenvironments: Bedroom, living room and kitchen

Exposure to particulate matter (PM) and its chemical constituents in residential microenvironments has become a major health concern worldwide. The oxidative potential (OP) has been proposed as a metric for estimating the PM capacity to induce oxidative stress and, consequently, health effects. In the present study, PM10 was daily monitored simultaneously in the bedroom, living room and kitchen of three dwellings for one week in a small town of Portugal, to perform a detailed characterisation of its organic and inorganic constituents and the determination of the OP. Bedrooms (B) were found to be a hotspot of PM10 concentrations (B1 = 22.7 μg m−3; B2 = 19.5 μg m−3; B3 = 68.1 μg m−3). PM10-bound elements varied significantly between microenvironments in all dwellings. Lower molecular weight polycyclic aromatic hydrocarbons (PAHs) were found to be between 14 and 72 times higher than high molecular weight PAHs in bedrooms. The mean volume-normalised OP determined by the dithiothreitol and ascorbic acid assays varied within the 0.01–0.38 nmol min−1 m−3 and 0.03–0.53 nmol min−1 m−3 ranges, respectively. Quinones, oxy-aromatic, aromatic and alkyl-aromatic compounds stood out in bedrooms. Strong and significantly positive relationship between OP and black carbon, Cu and Br were observed, indicating common redox active species mainly associated with traffic emissions. Sr, Fe, Zn and Zr presented higher concentrations in dwelling 3, exhibiting excellent positive correlation with OP, indicating that the Sahara dust intrusion recorded in that house may have contributed to the formation of more redox active species thought to drive antioxidant depletion responses.

Oxidation mechanism of sulfur-containing compounds and antioxidant depletion dynamics: Insights into interactions

Sulfur-containing compounds (SCCs) are the most abundant heteroatomic organic species (HOS) in petroleum fuels. This study investigates the dynamics of SCCs in surrogate fuel systems, focusing on their oxidation stability, reactivity, and interactions. An analysis of eleven selected SCCs, spanning both reactive (thiols, sulfides, and disulfides) and nonreactive (thiophenes and benzothiazole) species, was conducted at 140 °C. The investigation delves into reaction and degradation mechanisms, exploring resulting products, binary mixtures of reactive SCCs for potential interactions, and multicomponent SCC systems to understand nuanced interaction. Findings reveal unique reaction pathways in single-component SCCs, synergetic and antagonistic effects in binary mixtures, and substantial decreases in reaction rates in all multicomponent systems. Moreover, SCCs expedited antioxidant consumption, highlighting their pivotal role in fuel stability and degradation. The study contributes valuable insights into SCC dynamics, advocating further exploration of HOS’s interactions for enhanced fuel formulation and stability testing strategies.

Evaluation of Oxidative Stress, Anti-Oxidant, Vitamins and Co-Factor Elements in The Sera of Gastric Cancer in Iraqi Patients.

The objective of this study is to analyze oxidative stress markers Total Oxidant Status (TOS) and total Antioxidant Status (TAS), assess antioxidant levels (vitamin C, E), and evaluate co-factor element profiles zinc (Zn), copper (Cu), iron (Fe) in the serum of Iraqi gastric cancer patients. By elucidating these relationships, the research aims to enhance knowledge on oxidative stress, dietary factors, and potential therapeutic approaches for managing nutritional imbalances in this cohort. The study included 60 gastric cancer patients and 60 matched controls. Blood samples were collected and serum was extracted for analysis of TOS, TAS, Vitamin C, Vitamin E, copper, zinc, and iron levels. Measurements were conducted using spectrophotometry and ELISA kits from various companies. Statistical analysis was performed with IBM SPSS 25.0, presenting results as means ± SD, and differences between groups were assessed via independent samples t-test at p < 0.05 and p ≤ 0.01. The study results indicated statistically significant differences between gastric cancer patients and controls in various biomarkers, with all comparisons showing p-values less than 0.001. This suggests strong evidence for the observed differences between the two groups in (TOS), (TAS), vitamins C and E, Cu, Zn, and Fe levels. These relationships underscore the intricate connections among biomarkers in gastric cancer pathophysiology. The study underscores the intricate relationship between oxidative stress, antioxidant depletion, and micronutrient imbalances in gastric cancer. These findings offer valuable insights into the disease's pathophysiology, indicating potential diagnostic biomarkers. Further research is warranted to unravel underlying mechanisms and explore clinical applications for early gastric cancer diagnosis.

Antioxidant depletion from a 2 mm high-density polyethylene geomembrane used in brine containment

The depletion of antioxidants from a 2 mm high-density polyethylene geomembrane immersed in brine at seven temperatures (95, 85, 75, 65, 55, 40, and 25°C) for 28 months is reported. An Arrhenius model is used to predict the performance of the geomembrane at low site-specific temperatures. The antioxidant depletion times are reported for temperatures between 20 and 95°C. The solubility of the antioxidant and stabilizer packages, the oxidation by-products, and their susceptibility to hydrolysis are discussed. After 28 months of incubation, no oxidative degradation was observed for samples in the full brine solution even at 95°C. Morphological changes reduced the stress-crack resistance to a stable representative value without a reduction in the tensile elongation at break. The effect of the brine solution concentration on the depletion of antioxidants and stabilizers was investigated at 85°C. It was found that the depletion rate decreases with the increasing brine concentration.

Oxidative Stress and Annexin A2 Differential Expression in Free Fatty Acids-Induced Non-Alcoholic Fatty Liver Disease in HepG2 Cells.

Non-alcoholic fatty liver disease (NAFLD) is a rising global burden, affecting one in four adults. Despite the increasing prevalence of NAFLD, the exact cellular and molecular mechanisms remain unclear, and effective therapeutic strategies are still limited. In vitro models of NAFLD are critical to understanding the pathogenesis and searching for effective therapies; thus, we evaluated the effects of free fatty acids (FFAs) on NAFLD hallmarks and their association with the modulation of Annexin A2 (ANXA2) and Keratin 17 (KRT17) in HepG2 cells. Our results show that oleic and palmitic acids can differentially induce intracellular lipid accumulation, cell death, and promote oxidative stress by increasing lipid peroxidation, protein carbonylation, and antioxidant defense depletion. Moreover, a markedly increased expression of inflammatory cytokines demonstrated the activation of inflammation pathways associated with lipotoxicity and oxidative stress. ANXA2 overexpression and KRT17 nuclear translocation were also observed, supporting the role of both molecules in the progression of liver disease. Taken together, these data provide insights into the interplay between ANXA2 and KRT17 in NAFLD, paving the way for understanding molecular mechanisms involved with the disease and developing new therapeutic strategies.

Arsenic Induced Oxidative Neural-Damages in Rat are Mitigated by Tea-Leave Extract via MMPs and AChE Inactivation, Shown by Molecular Docking and in Vitro Studies with Pure Theaflavin and AChE.

Chronic arsenic-exposure causes neuromuscular disorders and other health anomalies. Damage to DNA and cytoskeletal/extracellular matrix is brought on by reactive-oxygen-species (ROS)-induced intrinsic antioxidant depletion (thiols/urate). Therapeutic chelating-agents have multiple side-effects. The protection of (Camellia sinensis) tea-extract and role of uric-acid (UA) or allopurinol (urate-depletor) on arsenic-toxicity were verified in rat model. Camellia sinensis (CS dry-leaves), UA or allopurinol was supplemented to arsenic-intoxicated rats for 4-weeks. Purified theaflavins and their galloyl-ester were tested in-vitro on pure AChE (acetylcholinesterase) and their PDB/PubChem 3-D structures were utilized for in-silico binding studies. The primary chemical components were evaluated from CS-extracts. Biochemical analysis, PAGE-zymogram, DNA-stability comet analysis, HE-staining was performed in arsenic-exposed rat brain tissues. Animals exposed to arsenic showed symptoms of erratic locomotion, decreased intrinsic antioxidants (catalase/SOD1/uric acid), increased AChE, and malondialdehyde. Cerebellar and cerebrum tissue damages were shown with increased levels of matrix-metalloprotease (MMP2/9) and DNA damage (comets). Allopurinol- supplemented group demonstrated somewhat similar biochemical responses. In the CS-group brain tissues especially cerebellum is considerably protected which is evident from endogenous antioxidant and DNA and cytoskeleton protection with concomitant inactivation of MMPs and AChE. Present study indicates theaflavin-digallate (TFDG) demonstrated the highest inhibition of purified AChE (IC50 = 2.19 µg/ml with the lowest binding free-energy; -369.87 kcal/mol) followed by TFMG (IC50 = 3.86 µg/ml, -347.06 kcal/mol) suggesting their possible restoring effects of cholinergic response. Favorable responses in UA-group and adverse outcome in allo-group justify the neuro-protective effects of UA as an endogenous antioxidant. Role of flavon-gallate in neuro protection mechanism may be further studied.

Biochemical and histological alterations induced by UV-328 in the gill tissue of Zebra fish (Danio rerio) and its reversal by Dimethoxy curcumin

The presence of Benzotriazole UV Stabilizer-328 (UV-328) in different biological and natural systems is of fast, regular concern in recent days due to their exuberant use in sunscreens. To learn more about its role of oxidative damage in the gills and to uncover the protective nature of DiMC, we evaluated its sub-lethal toxicity in Zebra fish gill tissue and also evaluated the potential defensive role of Dimethoxy curcumin (DiMC). Grown-up Zebra fish were exposed to 55 µg/L of UV-328 and 50mg/kg of DiMC for four weeks. After the completion of 28 days, gill tissues were dissected out and assessed for their response to oxidative stress, antioxidant enzymes status, and histopathological changes. Our results demonstrated that antioxidant such as glutathione (GSH) levels and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and Glutathione S-transferase (GST) were all diminished in the gill tissue along with the profound increase in lipid peroxidation (measured as TBARS) in the UV-328-treated group. Histopathological lesions, for instance, inflammatory cell infiltration with a minimal congestion in primary lamellae, diffuse epithelial hyperplasia and fusion of secondary lamellae, multifocal mucus cell hyperplasia were seen in the UV-328-treated gill tissue of Zebra fish. The UV-328-induced oxidative, biochemical, and histological alterations were almost reverted back to normal in the DiMC enhanced group, suggesting its remediative efficacy against UV-328-induced respirotoxicity. Based on our findings, exposure to UV-328, even at a low level, could be toxic, causing oxidative stress, antioxidant depletion, and pathological gill damage in Zebra fish. And these alterations were almost recuperated in DiMC supplemented group which signifies its protective influence against UV-328 toxicity. Keywords: UV-328; Oxidative stress; Antioxidants; Histopathology; Zebra fish

The Long-Term Performance of a High-Density Polyethylene Geomembrane with Non-Parametric Statistic Analysis and Its Contribution to the Sustainable Development Goals

The tailings from gold beneficiation can cause various negative impacts, necessitating measures to prevent their transport and environmental contamination. Geomembranes serve as hydraulic barriers in mining tailings reservoirs, thereby supporting the Sustainable Development Goals (SDGs). To ensure that the geomembrane effectively mitigates environmental impact, it is essential to study its durability when applied in the field. This article examines the long-term performance of an HDPE geomembrane exposed for 7 and 11 years at a gold mining tailing site in Brazil. Samples were exhumed from different locations at the dam, and their properties were evaluated. Non-parametric statistics were employed using the Kernel Density Estimator (KDE). For the 11-year-old geomembranes, the probability of the geomembrane reaching nominal failure in terms of tensile strength was 0.4%. The peel separation values exceeded the maximum allowable by the GRI GM13 standard. Although the geomembranes showed significant antioxidant depletion, suggesting they were close to or had already reached their residual stages, they approached nominal failure based on their stress crack resistance but did not rupture. The environmental analysis indicated no significant contamination in the area, corroborating that the geomembrane is fulfilling its function. The non-parametric methodology proved promising for durability analysis and could be applied to other engineering projects with geosynthetics, thereby adding reliability to decision-making in alignment with sustainable development.

Mitotherapy with Fresh Isolated Cardiac Mitochondria Via Injection Into Blood Reduces Aluminum Phosphide-Induced Mortality and Protects Cardiac Tissue Against Oxidative Stress and Mitochondrial Damages.

The hallmark of aluminum phosphide (AlP) poisoning is heart failure in victims which is associated with reactive oxygen species (ROS), mitochondrial dysfunction, oxidative stress, alteration in antioxidant defense system and depletion of ATP in cardiomyocytes. In the present study, we hypothesized that the injection of isolated mitochondria into blood or mitochondrial transplantation can likely create a primary target for phosphine released from AlP and inhibit AlP-induced mortality and cardiotoxicity in rat. Male, Wistar, healthy and adult rats were randomly divided into 5 groups as control, AlP (12.5 mg/kg, orally), AlP + mitochondria (125 µg/kg), AlP + mitochondria (250 µg/kg) and mitochondria (250 µg/kg) alone. Functional and intact mitochondria isolated from rat heart and transplantation was carried out via tail vein, 30 min after exposure to AlP. Survival rate, histopathological alterations, cardiac biochemical markers, oxidative stress and mitochondrial toxicity parameters were monitored and analyzed during 30 days. We found that injection of healthy mitochondria into blood at concentrations of 125 and 250 125 µg/ml significantly increased the survival of rats up to 40% and 56.25% respectively, during 30 days. Moreover, we observed that mitochondria injection into blood decreased histopathological damages, cardiac biochemical markers, oxidative stress and mitochondrial toxicity parameters. To our knowledge, the current study is the first report in the literature that demonstrated good therapeutic effects of mitochondrial transplantation in AlP-induced mortality and cardiotoxicity. The findings of the present study suggests that injection of exogenous mitochondria into blood could be an effective therapeutic strategy in treating AlP poisoning.

Cannabidiol effectively prevents oxidative stress and stabilizes hypoxia-inducible factor-1 alpha (HIF-1α) in an animal model of global hypoxia

Cannabidiol (CBD) is a non-psychotomimetic phytocannabinoid derived from Cannabis sativa. It has therapeutic effects in different paradigms of brain injury, acting as a neuroprotectant. As oxidative stress is a primary risk factor for brain damage after neonatal hypoxia, we tested the effect of CBD on oxidative status and non-protein-bound iron accumulation in the immature brain after hypoxia. Moreover, we tested whether cannabidiol affects the accumulation of hypoxia-inducible factor-1 alpha (HIF-1α) which plays a key role in the regulation of cellular adaptation to hypoxia and oxidative stress. We used 7-day-old mice randomly assigned to hypoxic or control groups. Immediately after hypoxia or control exposure, pups were randomly assigned to a vehicle or CBD treatment. 24 h later, they were decapitated and the brains were immediately removed and stored for further biochemical analyses. We found that CBD reduced lipid peroxidation and prevented antioxidant depletion. For the first time, we also demonstrated that CBD upregulated HIF-1α protein level. This study indicates that CBD may effective agent in attenuating the detrimental consequences of perinatal asphyxia.

Usnic acid alleviates inflammatory responses and induces apoptotic signaling through inhibiting NF-ĸB expressions in human oral carcinoma cells.

Usnic acid (UA) is a unique bioactive substance in lichen with potential anticancer properties. Recently, we have reported that UA can reduce 7,12-dimethylbenz[a] anthracene-induced oral carcinogenesis by inhibiting oxidative stress, inflammation, and cell proliferation in a male golden Syrian hamster in vivo model. The present study aims to explore the relevant mechanism of cell death induced by UA on human oral carcinoma (KB) cell line in an in vitro model. We found that UA can induce apoptosis (cell death) in KB cells by decreasing cell viability, increasing the production of reactive oxygen species (ROS), depolarizing mitochondrial membrane potential (MMP) levels, causing nuclear fragmentation, altering apoptotic morphology, and causing excessive DNA damage. Additionally, UA inhibits the expression of Bcl-2, a protein that promotes cell survival, while increasing the expression of p53, Bax, Cytochrome-c, Caspase-9, and 3 proteins in KB cells. UA also inhibits the expression of nuclear factor-κB (NF-κB), a protein that mediates the activation of pro-inflammatory cytokines such as TNF-α and IL-6, in KB cells. Furthermore, UA promotes apoptosis by enhancing the mitochondrial-mediated apoptotic mechanism through oxidative stress, depletion of cellular antioxidants, and an inflammatory response. Ultimately, the findings of this study suggest that UA may have potential as an anticancer therapeutic agent for oral cancer treatments.

Palliative effects of carnosol on lung-deposited pollutant particles-induced thrombogenicity and vascular injury in mice.

The toxicity of inhaled particulate air pollution perseveres even at lower concentrations than those of the existing air quality limit. Therefore, the identification of safe and effective measures against pollutant particles-induced vascular toxicity is warranted. Carnosol is a bioactive phenolic diterpene found in rosemary herb, with anti-inflammatory and antioxidant actions. However, its possible protective effect on the thrombotic and vascular injury induced by diesel exhaust particles (DEP) has not been studied before. We assessed here the potential alleviating effect of carnosol (20 mg/kg) administered intraperitoneally 1 h before intratracheal (i.t.) instillation of DEP (20 μg/mouse). Twenty-four hours after the administration of DEP, various parameters were assessed. Carnosol administration prevented the increase in the plasma concentrations of C-reactive protein, fibrinogen, and tissue factor induced by DEP exposure. Carnosol inhibited DEP-induced prothrombotic effects in pial microvessels invivo and platelet aggregation invitro. The shortening of activated partial thromboplastin time and prothrombin time induced by DEP was abated by carnosol administration. Carnosol inhibited the increase in pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor α) and adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and P-selectin) in aortic tissue. Moreover, it averted the effects of DEP-induced increase of thiobarbituric acid reactive substances, depletion of antioxidants and DNA damage in the aortic tissue. Likewise, carnosol prevented the decrease in the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) caused by DEP. We conclude that carnosol alleviates DEP-induced thrombogenicity and vascular inflammation, oxidative damage, and DNA injury through Nrf2 and HO-1 activation.

Protective effect of cinnamon extract against cobalt-induced multiple organ damage in rats.

The role of oxidative stress and inflammation in cobalt (Co) toxicity has been the focus of previous studies. Cinnamon and its main components have been reported to have protective effects in various tissues with antioxidant and anti-inflammatory effects. In this study, the protective effect of cinnamon extract (CE) against possible Co-induced heart, kidney, and liver damage in rats was investigated biochemically. Eighteen albino Wistar-type male rats were categorized into three groups (n = 6 per group): control (CG), CoCL2-administered (CoCL2), and CE + CoCL2-administered (CE + Co) groups. The CE + CoCL2 group was administered CE (100mg/kg), and the CoCL2 and CG groups were administered distilled water orally by gavage. One hour after the administration, Co (150mg/kg) was administered orally to the CE + CoCL2 and CoCL2 groups. This procedure was repeated once daily for 7days. Then, biochemical markers were studied in the excised heart, kidney, and liver tissues. CoCL2 increased oxidants and proinflammatory cytokines and decreased antioxidants in heart, kidney, and liver tissues. Heart, kidney, and liver tissue were affected by Co damage. CE treatment suppressed the CoCL2-induced increase in oxidants and proinflammatory cytokines and decrease in antioxidants in heart, kidney, and liver tissues. CE treatment has been shown to attenuate cardiac damage by reducing serum troponin I (TpI) and creatine kinase-MB (CK-MB), renal damage by reducing creatinine and blood urea nitrogen (BUN), and liver damage by reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Co induced the production of oxidants and proinflammatory parameters and antioxidant depletion in heart, kidney, and liver tissues of rats. Our experimental results show that CE protects heart, kidney, and liver tissues against oxidative and inflammatory changes induced by CoCLl2.

Targeted Metabolomics Highlights Dramatic Antioxidant Depletion, Increased Oxidative/Nitrosative Stress and Altered Purine and Pyrimidine Concentrations in Serum of Primary Myelofibrosis Patients.

To date, little is known concerning the circulating levels of biochemically relevant metabolites (antioxidants, oxidative/nitrosative stress biomarkers, purines, and pyrimidines) in patients with primary myelofibrosis (PMF), a rare form of myeloproliferative tumor causing a dramatic decrease in erythropoiesis and angiogenesis. In this study, using a targeted metabolomic approach, serum samples of 22 PMF patients and of 22 control healthy donors were analyzed to quantify the circulating concentrations of hypoxanthine, xanthine, uric acid (as representative purines), uracil, β-pseudouridine, uridine (as representative pyrimidines), reduced glutathione (GSH), ascorbic acid (as two of the main water-soluble antioxidants), malondialdehyde, nitrite, nitrate (as oxidative/nitrosative stress biomarkers) and creatinine, using well-established HPLC method for their determination. Results showed that PMF patients have dramatic depletions of both ascorbic acid and GSH (37.3- and 3.81-times lower circulating concentrations, respectively, than those recorded in healthy controls, p < 0.0001), accompanied by significant increases in malondialdehyde (MDA) and nitrite + nitrate (4.73- and 1.66-times higher circulating concentrations, respectively, than those recorded in healthy controls, p < 0.0001). Additionally, PMF patients have remarkable alterations of circulating purines, pyrimidines, and creatinine, suggesting potential mitochondrial dysfunctions causing energy metabolism imbalance and consequent increases in these cell energy-related compounds. Overall, these results, besides evidencing previously unknown serum metabolic alterations in PMF patients, suggest that the determination of serum levels of the aforementioned compounds may be useful to evaluate PMF patients on hospital admission for adjunctive therapies aimed at recovering their correct antioxidant status, as well as to monitor patients' status and potential pharmacological treatments.

Oxidative Stress and Antioxidant Status in Adult Patients with Transfusion-Dependent Thalassemia: Correlation with Demographic, Laboratory, and Clinical Biomarkers.

Iron overload in beta transfusion-dependent thalassemia (β-TDT) may provoke oxidative stress and reduction of the antioxidant defenses, with serious consequences for the disease course and complications. The present study evaluated the oxidant/antioxidant status of β-TDT patients and its correlation with demographic, clinical, laboratory, and instrumental biomarkers. The OXY-adsorbent assay and the d-ROMs (Diacron, Grosseto, Italy) were evaluated in 58 β-TDT patients (mean age: 37.55 ± 7.83 years, 28 females) enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Iron overload was quantified with R2* magnetic resonance imaging. Mean OXY was 323.75 ± 113.19 μmol HClO/mL and 39 (67.2%) patients showed a decreased OXY-Adsorbent level (<350 μmol HClO/mL), of whom 22 (37.9%) showed severely reduced levels. Mean d-ROMs was 305.12 ± 62.19 UA; 12 (20.7%) patients showed oxidative stress, and 4 (6.9%) elevated oxidative stress. OXY showed a significant negative correlation with global and segmental cardiac iron levels. D-ROMs levels significantly correlated with markers of cardiovascular risk (aging, glycemia, and N-terminal pro-B-type natriuretic peptide). Antioxidant depletion is frequent in β-TDT patients, where OXY might serve as additive biomarker to assess heart iron status, whereas the d-ROMs might be helpful to assess the cardiovascular risk burden.

Long-term Performance of Textured HDPE Geomembranes in Municipal Solid Waste Landfills

The effect of texturing (co-extrusion using a blowing agent) on the long-term performance of geomembranes immersed in synthetic municipal solid waste (MSW) leachate is examined over an approximately 8-year period. Antioxidant depletion of the textured part is shown to be much faster than that of the smooth edge. Likewise, the degradation in the tensile break properties at 85°C is faster for the textured part than for the smooth edge portion and smooth equivalent. The updated estimates for antioxidant depletion time based on data at four different temperatures (40, 55, 75, and 85°C) over 98 months of data collection are compared with predictions based on 34 months of data and the implications are discussed. Nominal failure was reached at 75°C, and this combined with data at 85°C allows prediction of the time between depletion of Std-OIT and nominal failure at lower temperatures. The effect of salt concentration in incubation fluid on the time to degradation is examined. Finally, the paper comments on the uses of textured versus smooth geomembrane.&#x0D;

Assessment of interactions between elemental carbon and metals in black carbon: Hydroxyl radical generation and glutathione depletion

Elemental carbon (EC) and metals are two important parts of atmospheric black carbon (BC). However, little information is available regarding the interaction between them and its impacts on the reactive oxygen species (ROS) formation and physiological antioxidants depletion. In this study, we chose six most frequently detected metals (Cu(Ⅱ), Fe(Ⅲ), Mn(Ⅱ), Cr(Ⅲ), Pb(Ⅱ) and Zn(Ⅱ)) in BC and examined their interactions with EC in the ROS generation and glutathione (GSH) oxidation. Results showed that only Cu(Ⅱ) and EC synergically promoted the GSH oxidation and hydroxyl radical (•OH) generation. Other five metals had negligible effects on the GSH oxidation regardless of the presence or absence of EC. The synergistic interaction between Cu(Ⅱ) and EC could be attributed to the superior electrical conductivity of EC. In the process, EC transferred electrons from the adjacent GSH to Cu(Ⅱ) through its graphitic carbon framework to yield Cu(Ⅰ) and GSH radical. Cu(Ⅰ) further reacted with dioxygen to generate •OH, which eventually led to the oxidation of GSH. Our results revealed a new driving force inducing the ROS formation and GSH depletion as well as provided novel insights into the risk assessment of BC.