J.M.C. Gutteridge's research while affiliated with National Institute for Biological Standards and Control and other places
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Publications (340)
In recent years, there has been an explosion of interest about the use of `antioxidant' nutritional supplements. Do they really defend the body against diseases? Should we all be taking vitamin E, vitamin C, or more of certain polyunsaturated fats? Written by two leading experts in the field of free radicals in biology and medicine, this book unrav...
Phagocytic cells know exactly where an infection is by following chemotactic signals. The phagocytosis of bacteria results in a 'respiratory burst' in which superoxide radicals are released. We have previously compared the release of reactive oxygen species (ROS) by antibiotics, during electron transfer reactions, to this event. Antibiotics in thei...
The first life forms evolved in a highly reducing environment. This reduced state is still carried by cells today, which makes the concept of "reductive stress" somewhat redundant. When oxygen became abundant on the Earth, due to the evolution of photosynthesis, life forms had to adapt or become extinct. Living organisms did adapt, proliferated and...
There is an industry-driven public obsession with antioxidants, which are equated to safe, health-giving molecules to be swallowed as mega-dose supplements or in fortified foods. Sometimes they are good for you, but sometimes they may not be, and pro-oxidants can be better for you in some circumstances. This article re-examines and challenges some...
We aimed to quantify concentrations of inducible heme oxygenase (HO)-1 in the lungs of patients with acute respiratory distress syndrome (ARDS) and to investigate its role as a source of ferrous iron and as a signaling agent for iron regulation. Control of such processes by heme oxygenase has implications for the onset, progression, and resolution...
To ascertain the influence of albumin on antioxidant status in patients with acute lung injury.
Prospective, randomized, placebo-controlled study.
Intensive care units, teaching hospitals.
Twenty patients meeting the American European Consensus criteria for acute lung injury.
Ten patients received albumin (25 g of a 25% solution every 8 hrs for a t...
Acute respiratory distress syndrome (ARDS) is associated with altered plasma and lung iron chemistry. Iron can promote microbial virulence and catalyse pro-oxidant reactions, thereby contributing to the oxidative stress that characterises the syndrome. Therefore, the expression of ferritin and transferrin receptors (TfR) were sought in the lungs an...
Iron is an element essential for the survival of most aerobic organisms. However, when its availability is not adequately controlled, iron, can catalyze the formation of a range of aggressive and damaging reactive oxygen species, and act as a microbial growth promoter. Depending on the concentrations formed such species can cause molecular damage o...
To assess antioxidant protection against iron-catalyzed reactive oxygen species in meningococcal sepsis and to establish whether severity of illness is related to deficiencies in these antioxidant systems.
Prospective, controlled study.
Pediatric intensive care unit of a postgraduate teaching hospital.
Twenty children aged 6 months to 15 yrs (media...
Cleavage of an asparagine-linked sugar chain by hydrogen peroxide (H2O2) and a copper salt was investigated. Incubation of a 2-aminopyridine (PA)-labeled biantennary sugar chain, GlcNAcbeta1-2Manalpha1-6(GlcNAcbeta1-2Manalpha1-3)Manbeta1-4GlcNAcbeta1-4GlcNAc-PA, with H2O2 and Cu2+ led to formation of four major degradation products. Reversed phase...
Conventional cardiopulmonary bypass surgery (CCPB) increases the iron loading of plasma transferrin often to a state of plasma iron overload, with the presence of low molecular mass iron. Such iron is a potential risk factor for oxidative stress and microbial virulence. Here we assess 'off-pump' coronary artery surgery on the beating heart for chan...
Reactive oxygen (ROS) and reactive nitrogen species (RNS) produced in vivo at levels that cannot be dealt with adequately by endogenous antioxidant systems can lead to the damage of lipids, proteins, carbohydrates and nucleic acids. Oxidative modification of these molecules by toxic levels of ROS and RNS represents an extreme event that can lead to...
Iron is an essential requirement for the growth, development, and long term survival of most aerobic organisms. When control over safe iron sequestration is lost or compromised, leading to the release of low molecular mass forms of iron, the heart appears to be particularly sensitive to iron toxicity with cardiomyopathies often developing as a cons...
Reactive oxygen species produced at toxic levels are damaging species. When produced at sub-toxic levels, however, they are involved as second messengers in numerous signal transduction pathways. In addition to these findings, we can add the concept that iron (often viewed as the "villain" in free radical biology) can also be considered as a signal...
Patients with ARDS are known to be subjected to oxidative stress which is implicated in the pathophysiology of the injury. Inducible haem oxygenase (HO-1) catalyses the conversion of haem to biliverdin, carbon monoxide and iron, and is up-regulated by oxidative stress. HO-1 expression is thought to have beneficial effects, however, over- expression...
Patients with ARDS have well described abnormalities of plasma and BAL iron chemistry. Low molecular mass iron (LMrFe) is both pro-oxidant and a microbial virulence factor. Thus, abnormalities in the metabolism of iron may have profound implications in ARDS. We have shown previously that in a rodent model of sepsis ferritin and transferrin receptor...
The neutrophil enzyme myeloperoxidase (MPO) purposefully makes hypochlorous acid (HOCl) as part of the cells defence against microbial infections. During cell lysis, however, MPO will be released into the extracellular environment where production of HOCl, a powerful oxidant, will lead to molecular damage. Extracellular MPO binds to the copper-cont...
Cardiopulmonary bypass (CPB) surgery is often associated with mild lung injury and in some patients leads to acute lung injury and acute respiratory distress syndrome (ARDS). Aberrant plasma iron chemistry (increased iron loading of transferrin and/or the presence of redox-active low molecular mass iron) and increased plasma thiol levels are featur...
Experimental Protocols for Reactive Oxygen and Nitrogen Species is a translated, expanded, and fully updated of the Japanese book Experimental Protocols for Reactive Oxygen Research: assay methods, gene analysis, and pathophysiology models published in 1994. The aim of the book is to provide experimental protocols covering many aspects of free radi...
Experimental Protocols for Reactive Oxygen and Nitrogen Species is a translated, expanded, and fully updated of the Japanese book Experimental Protocols for Reactive Oxygen Research: assay methods, gene analysis, and pathophysiology models published in 1994. The aim of the book is to provide experimental protocols covering many aspects of free radi...
Experimental Protocols for Reactive Oxygen and Nitrogen Species is a translated, expanded, and fully updated of the Japanese book Experimental Protocols for Reactive Oxygen Research: assay methods, gene analysis, and pathophysiology models published in 1994. The aim of the book is to provide experimental protocols covering many aspects of free radi...
Experimental Protocols for Reactive Oxygen and Nitrogen Species is a translated, expanded, and fully updated of the Japanese book Experimental Protocols for Reactive Oxygen Research: assay methods, gene analysis, and pathophysiology models published in 1994. The aim of the book is to provide experimental protocols covering many aspects of free radi...
Experimental Protocols for Reactive Oxygen and Nitrogen Species is a translated, expanded, and fully updated of the Japanese book Experimental Protocols for Reactive Oxygen Research: assay methods, gene analysis, and pathophysiology models published in 1994. The aim of the book is to provide experimental protocols covering many aspects of free radi...
Experimental Protocols for Reactive Oxygen and Nitrogen Species is a translated, expanded, and fully updated of the Japanese book Experimental Protocols for Reactive Oxygen Research: assay methods, gene analysis, and pathophysiology models published in 1994. The aim of the book is to provide experimental protocols covering many aspects of free radi...
Experimental Protocols for Reactive Oxygen and Nitrogen Species is a translated, expanded, and fully updated of the Japanese book Experimental Protocols for Reactive Oxygen Research: assay methods, gene analysis, and pathophysiology models published in 1994. The aim of the book is to provide experimental protocols covering many aspects of free radi...
Experimental Protocols for Reactive Oxygen and Nitrogen Species is a translated, expanded, and fully updated of the Japanese book Experimental Protocols for Reactive Oxygen Research: assay methods, gene analysis, and pathophysiology models published in 1994. The aim of the book is to provide experimental protocols covering many aspects of free radi...
Experimental Protocols for Reactive Oxygen and Nitrogen Species is a translated, expanded, and fully updated of the Japanese book Experimental Protocols for Reactive Oxygen Research: assay methods, gene analysis, and pathophysiology models published in 1994. The aim of the book is to provide experimental protocols covering many aspects of free radi...
Experimental Protocols for Reactive Oxygen and Nitrogen Species is a translated, expanded, and fully updated of the Japanese book Experimental Protocols for Reactive Oxygen Research: assay methods, gene analysis, and pathophysiology models published in 1994. The aim of the book is to provide experimental protocols covering many aspects of free radi...
Experimental Protocols for Reactive Oxygen and Nitrogen Species is a translated, expanded, and fully updated of the Japanese book Experimental Protocols for Reactive Oxygen Research: assay methods, gene analysis, and pathophysiology models published in 1994. The aim of the book is to provide experimental protocols covering many aspects of free radi...
Experimental Protocols for Reactive Oxygen and Nitrogen Species is a translated, expanded, and fully updated of the Japanese book Experimental Protocols for Reactive Oxygen Research: assay methods, gene analysis, and pathophysiology models published in 1994. The aim of the book is to provide experimental protocols covering many aspects of free radi...
Experimental Protocols for Reactive Oxygen and Nitrogen Species is a translated, expanded, and fully updated of the Japanese book Experimental Protocols for Reactive Oxygen Research: assay methods, gene analysis, and pathophysiology models published in 1994. The aim of the book is to provide experimental protocols covering many aspects of free radi...
Experimental Protocols for Reactive Oxygen and Nitrogen Species is a translated, expanded, and fully updated of the Japanese book Experimental Protocols for Reactive Oxygen Research: assay methods, gene analysis, and pathophysiology models published in 1994. The aim of the book is to provide experimental protocols covering many aspects of free radi...
Experimental Protocols for Reactive Oxygen and Nitrogen Species is a translated, expanded, and fully updated of the Japanese book Experimental Protocols for Reactive Oxygen Research: assay methods, gene analysis, and pathophysiology models published in 1994. The aim of the book is to provide experimental protocols covering many aspects of free radi...
Pathological changes in iron status are known to occur during bypass and will be superimposed upon physiological abnormalities in iron distribution, characteristic of the neonatal period. We have sought to define the severity of iron overload in these patients. Plasma samples from 65 paediatric patients undergoing cardiopulmonary bypass (CPB) were...
In the late 1950's free radicals and antioxidants were almost unheard of in the clinical and biological sciences but chemists had known about them for years in the context of radiation, polymer and combustion technology. Daniel Gilbert, Rebeca Gerschman and their colleagues related the toxic effects of elevated oxygen levels on aerobes to those of...
Patients with ARDS are subjected to oxidative stress both by the nature of the condition and the supporting interventions required (eg hyperoxia). Haem oxygenase 1 (HO-1) is a heat shock protein up-regulated by oxidative stress, and may offer antioxidant protection. However, others suggest that HO-1 may under certain circumstances have deleterious...
Haem oxygenase-1 (HO-1) is a highly inducible stress protein that removes haem from cells with the release of biliverdin, carbon monoxide and low-molecular-mass iron (LMrFe). Several antioxidant functions have been ascribed to HO; its induction is considered to be a protective event. However, LMrFe produced during haem catabolism might elicit a pro...
Patients with sepsis frequently develop multiple organ failure (MOF) which has a high associated mortality. The lung is the commonest organ to be thus afflicted, the acute respiratory distress syndrome (ARDS) developing in some 40% of patients with sepsis. Why the lung should be particularly susceptible to the septic process is unclear. Low molecul...
The copper-containing plasma protein caeruloplasmin (Cp) has been shown to possess several oxidase activities, but with the exception of its ferrous ion oxidising (ferroxidase) activity which so far appear to be of minor biological relevance. Recently, Kim and colleagues (Kim et al. (1998) FEBS Lett. 431, pp. 473-475) observed that Cp can catalytic...
To assess the degree, source, and patterns of oxidative damage to bronchoalveolar lavage proteins as a modification of amino acid residues in patients with acute respiratory distress syndrome (ARDS).
Prospective, controlled study.
Adult intensive care unit of a postgraduate teaching hospital.
Twenty-eight patients with established ARDS were studied...
Inhaled nitric oxide (.NO) is used to improve gas exchange and reduce pulmonary vascular resistance (PVR) in patients with the acute respiratory distress syndrome (ARDS). Although controlled studies have shown no survival benefit, some investigators have suggested that inhaled.NO may have antiinflammatory properties under these circumstances. In co...
Cardiopulmonary bypass surgery is associated with the release of low molecular mass iron, which increases the saturation of plasma transferrin to over 50% in all adult patients treated. In a significant minority, however plasma transferrin becomes 100% iron saturated and non-transferrin bound iron can be detected in the plasma. An iron-saturated tr...
Haem oxygenase-1 is upregulated by numerous insults, including oxidative stress, and under such circumstances it is considered to be a protective stratagem. We have measured the haem oxygenase-1 expression in heart, lung and liver tissues of control and iron-overloaded rats. Lung tissue from iron-overloaded rats displayed a significant increase in...
Patients undergoing cardiopulmonary bypass (CPB) are subjected to severe oxidative stress, and frequently show evidence of acute lung injury post surgery. Associations between acute lung injury, oxidative stress, and aberrant ATP catabolism have been made and prompted us to consider whether the purine metabolites xanthine and hypoxanthine alter sig...
Adult patients undergoing cardiopulmonary bypass (CPB) surgery are subjected to increased oxidative stress and show a spectrum of lung injury. Increased levels of hydrogen peroxide (H2O2) are often seen during episodes of oxidative stress, such as the use of high FiO2s, and this molecule plays a key role in the formation of highly damaging oxidants...
The majority of deaths amongst critically ill patients requiring intensive care are attributable to sepsis and its sequelae: septic shock, the systemic inflammatory response syndrome (SIRS) and the acute respiratory distress syndrome (ARDS). Clinically, sepsis/SIRS and ARDS are characterised by disordered vascular control, manifest as systemic hypo...
In normal health, there is a balance between the formation of oxidising chemical species and their effective removal by protective antioxidants. Antioxidants are a diverse group of molecules with diverse functions. For example, they range from large highly specific proteinaceous molecules with catalytic properties to small lipid- and water-soluble...
1. Oxygen is a toxic gas - an introductionto oxygen toxicity and reactive species 2. The chemistry of free radicals and related 'reactive species' 3. Antioxidant defences Endogenous and Diet Derived 4. Cellular responses to oxidative stress: adaptation, damage, repair, senescence and death 5. Measurement of reactive species 6. Reactive species can...
The acute respiratory distress syndrome (ARDS) is known to be associated with increased oxidative stress. Heme oxygenase (HO) catalyses the intracellular breakdown of heme proteins to biliverdin and bilirubin, with the release of carbon monoxide and free iron. HO-1, a heat shock protein (hsp32), is widely induced under conditions of oxidative stres...
1.Albumin is often administered intravenously to critically ill patients as a volume expander, to combat hypoalbuminaemia, and to decrease hyperbilirubinaemia. There is, however, an ongoing debate concerning the therapeutic benefit of the former which is an expensive form of treatment.
2.Albumin has several biological functions, in particular as a...
Most of copper present in rat plasma and liver binds to caeruloplasmin and metallothionein, respectively, and is not redox active. However, free forms of copper including loosely bound forms to other molecules are redox active. We assessed the free copper in Long-Evans rats with a cinnamon-like coat color (LEC rats), an animal model of Wilson disea...
Low molecular mass iron (LMrFe) can appear in plasma when the transferrin becomes fully iron loaded. Such iron poses a risk factor for oxidative damage, and for microbial virulence. A previous novel approach to the detection and measurement of LMrFe in plasma was the use of the iron-binding properties of the glycopeptide antitumour antibiotic bleom...
Ferric ions bind to citrate and undergo an autoreduction to form a ferrous-citrate complex, greatly increasing the redox activity of the iron complex. Ferrous ions and citrate are also essential for the enzymic activity of aconitase. Aconitase, with its iron-sulphur cluster has a versatile structure which allows it to act as an iron regulatory prot...
The acute respiratory distress syndrome (ARDS) in adults is associated with a wide variety of precipitating factors, often not directly involving the lung, and has an associated mortality of 50-80%. ARDS is almost invariably associated with sepsis, either as an initiating factor or as a secondary complication, which increases the expression of a nu...
A wide variety of extracted and synthesised drug molecules have electron transfer capabilities which allow them to generate reactive oxygen species (ROS). In particular, many antibiotics that kill or inhibit bacteria, yeasts and cancer cells readily transfer electrons to oxygen making superoxide and hydrogen peroxide in the process. When suitable r...
The formation of reactive oxygen species (ROS), leading to increased oxidative stress has been implicated as a contributing
factor to the development and progression of ARDS. Evidence of increased oxidative damage to lipids and proteins has been
found in the plasma of patients with ARDS, together with low or compromised antioxidant protection. Oxid...
Haem oxygenase catalyses the conversion of haem to biliverdin, free iron, and CO. It exists in two isoforms, one is constitutively expressed (HO-2), the other (HO-1) is induced by a variety of stresses including haem, endotoxin and hyperthermia. HO-1 is a heat shock protein (HSP) and is known as HSP 32. Evidence, suggests that haem oxygenase, has a...
Reactive oxygen species (ROS) have been implicated in the pathophysiology of lung surgery associated with ischaemia/reperfusion. ROS produced by activated neutrophils are often involved in various forms of alveolar injury. Hydrogen peroxide (H2O2) produced by such neutrophils can enter the gas phase at physiological temperatures. To study this we m...
Heme oxygenase is the microsomal-bound enzyme responsible for cleavage of heme to biliverdin, with the concomitant release of free iron and carbon monoxide. Two isoforms have been identified and cloned: HO-1 (inducible) and HO-2 (constitutive). HO-1 (heat shock protein 32) is induced by various forms of oxidative stress, where it is thought to have...
To assess plasma iron status in critically ill patients with septic shock.
Observational, prospective study.
Adult intensive care units in teaching and tertiary referral hospitals.
Fifteen adult patients with established septic shock. Normal control subjects (n = 10) were also investigated. Data from patients and controls were compared with previou...
To assess the relationship between oxidative stress resulting from cardiopulmonary bypass and the onset of increased pulmonary vascular permeability.
Prospective, controlled study.
Adult intensive care unit of a postgraduate teaching hospital.
Ten patients undergoing surgery requiring cardiopulmonary bypass, and seven normal subjects.
Cardiopulmona...
Acute respiratory distress syndrome in adults (ARDS) carries a high mortality. Patients with ARDS experience severe oxidative stress from neutrophil activation, and from treatment with high inspired oxygen concentrations (F(I)O2). Oxidative stress arises from an increased generation of reactive oxygen species (ROS) which overwhelm existing antioxid...
Plasma from certain preterm and term babies has recently been shown to contain low molecular mass iron (LMrFe) that can be chelated and measured in the bleomycin assay. The chemical nature of such iron, when detected in biological fluids, is still unclear with suggestions that it may not be a redox active form of iron until it becomes bound to bleo...
This chapter describes basic principles of oxidative stress, brain iron, and neurodegeneration. Superoxide dismutases (SODs) are enzymes that are an important defence against O2 toxicity. This antioxidant role of SODs is supported by a wide range of evidence including results obtained using the techniques of modern molecular biology. Two-thirds of...
Xanthine oxidase (XOD) has been implicated as a source of reactive oxygen species (ROS) in vivo, and may contribute to oxidative damage associated with some disease states including ARDS.It is formed from the dehydrogenase form of the enzyme (XDH) by a variety of causes including ischaemia/reperfusion and hypoxia. XOD utilises its substrates hypoxa...
Bronchoalveolar lavage (BAL) provides a sample of lung surface lining fluid. Several pulmonary diseases appear to involve tissue damage caused by reactive oxygen species generated by inhaled oxidants or by phagocytic cells activated within the lung. We show that BAL from normal healthy controls contain chelatable redox active iron that is pro-oxida...
There is a strong evidence that adult patients with acute respiratory distress syndrome (ARDS) are under severe oxidative stress, which leads to molecular damage. Using gas chromatography-mass spectrometry, our objective was to sequentially monitor changes, in intensive care unit (ICU) patients, characteristic of the oxidative loss of plasma unsatu...
Citations
... The superoxide anion radicals (O 2 •− ) were generated photochemically (by using a mercury lamp) in a medium containing: 50 mM phosphate buffer, pH 7.8; 1.17 × 10 −6 M riboflavin; 0.2 mM methionine; 2 × 10 −5 M KCN and 5.6 × 10 −5 M nitro-blue tetrazolium (NBT) [38] . The generated O 2 •− reduce the presented in the medium nitro-blue tetrazolium (NTB) to produce blue colored formazan. ...
... MDA was estimated by following the method of Ohkawa et al. (1979). H 2 O 2 was determined in accordance to Gutteridge and Quilan (2000). ...
... This increased risk may be associated in part with the failure to expand maternal plasma volume adequately, thus diminishing appropriate placental perfusion 3,4,5 . Although controlled methods of iron supplementation during pregnancy have consistently demonstrated positive effects on maternal iron status at delivery, they have shown reductions in factors that are associated with anemia, for example increased risk of preterm delivery and infant low birth weight 1,3,4,6,7 . ...
... Against microbial invasion, disease, and pollutant toxicity, oxidative stress activates defensive mechanisms in macrophages and neutrophils. Given the Fenton reaction's iron, which generates hydroxyl radicals, Fe 2+ (free iron) is a crucial component connected to ROS generation's toxicity [128,129]. ...
... The liver and jejunum samples were minced and homogenized in 10 volumes (liver) and 5 volumes (jejunum) of 25 mmol/L sucrose with 10 mmol/L Tris-HCl, pH 7.5, supplemented with 1×phosphatase inhibitor mix I and 1×protease inhibitor mix G at 1500 rpm using the IKA-Werk Ultra-Turrax homogenizer from Janke & Kunkel (Staufen, Germany) at 4 • C. The homogenates were sonicated on ice at 10 kHz for 30 s (Bandeline Sonopuls HD 2070) followed by centrifugation in a Beckman ultracentrifuge at 100,000× g for 90 min at 4 • C [63]. The supernatants obtained were used for the biochemical analyses. ...
... Several reports have demonstrated that DT content was significantly higher in the aortic tissue of hyperglycemic animals [62], and that urinary DT excretion was increased in people with diabetes [63], and in children with an autism spectrum disorder [64]. It is considered that protein contained in food can be oxidized when cooked, and low levels of DT, as well nitrotyrosine and o-tyrosine are found in many normal body tissues [19,65]. Why urinary DT level was associated with higher vegetable consumption in the current study is unclear. ...
... When present in low to moderate concentrations, free radicals such as superoxide (O 2 •− ), hydroxyl radicals ( • OH), and singlet oxygen ( 1 O 2 ) are essential in regulating various physiological functions of the body. 20 However, owing to their unpaired electron, they are extremely reactive with other cellular molecules and can hamper the body's antioxidant defense systems, thereby leading to oxidative stress. 21 DOX promotes oxidative stress by the formation of a semiquinone derivative via an NADPHdependent reduction reaction. ...
... Antioxidants protect against oxidative stress by interrupting the propagation of free radicals or inhibiting the formation of free radicals. Oxidative stress has been implicated in the genesis and progression of various human diseases and conditions, including diabetes, arthritis, cancer, atherosclerosis, heart attack, Alzheimer's disease, Parkinson's, and many more [11][12][13][14]. Clinical research reveals that consuming foods rich in antioxidants and polyphenols boosts the antioxidant capacity of our body and reduces the damage caused by oxidative stress [15][16][17][18][19]. us, including plant-based antioxidant-rich nutrients in our diet can help prevent us from various chronic diseases. ...
... Ascorbic acid (vitamin C) is an essential dietary micronutrient required for a variety of biological functions. It primarily functions as a cofactor for many enzymes, such as the prolyl and lysyl hydroxylases which are involved in collagen biosynthesis (Halliwell and Gutteridge, 2015c). A deficiency in vitamin C causes the disease scurvy. ...
... Copper via changing its oxidation state catalyzes the conversion of two O 2 •radicals and two H + to H 2 O 2 and O 2 (Halliwell and Gutteridge, 2015). ...
