Thrombosis is a common disorder with a relevant burden of morbidity and mortality worldwide, particularly among elderly patients. Growing evidence demonstrated a direct role of oxidative stress in thrombosis, with various cell types contributing to this process. Among them, erythrocytes produce high quantities of intracellular reactive oxygen species (ROS) by NADPH oxidase activation and haemoglobin autoxidation. Concomitantly, extracellular ROS released by other cells in the blood flow can be uptaken and accumulate within erythrocytes. This oxidative milieu can alter erythrocyte membrane structure, leading to an impaired erythrocyte function, and promoting erythrocytes lysis, binding to endothelial cells, activation of platelet and of coagulation factors, phosphatidylserine exposure and release of microvesicles. Moreover, these abnormal erythrocytes are able to adhere to the vessel wall, contributing to thrombin generation within the thrombus. This process results in accelerated haemolysis and in a hypercoagulable state, in which structurally impaired erythrocytes contribute to increase thrombus size, to reduce its permeability and susceptibility to lysis. However, the wide plethora of mechanisms by which oxidised erythrocytes contribute to thrombosis is not completely elucidated. This review discusses the main biochemical aspects linking erythrocytes, oxidative stress and thrombosis, addressing their potential implication for clinical and therapeutic management.

In this work, we evaluated the short time-induced oxidative stress–mediated rapid metabolic and physiological responses of resistant and susceptible Sumatran fleabane [Conyza sumatrensis (Retz.) E. Walker; syn.: Erigeron sumatrensis Retz.] to 2,4-D herbicide. Under fixed conditions (25 C and 65 ± 5% relative humidity), we assayed injury symptoms, chlorophyll a fluorescence, and antioxidative systems of biotypes both resistant and susceptible to 2,4-D (1,005 g ae ha−1). Under 15 versus 25 C temperatures and light and dark conditions, oxidative stress–mediated damage was assayed on plants that received 2,4-D herbicide applications. The injury symptoms observed in the 2,4-D–resistant biotype were rapid necrosis in leaves within 30 min, with the reestablishment of normal growth within 1 to 2 wk after 2,4-D treatment. The basal antioxidant enzyme activities of superoxide dismutase, catalase, and ascorbate peroxidase were greater in the resistant than in the susceptible biotype, although the activities of all enzymes generally did not differ between untreated and treated in the resistant biotype. The resistant biotype showed great reduction (at 1 and 4 h after application) in the photosynthetic electron transport chain performance index, while these metabolic changes were only detected after 4 h in the susceptible biotype. The resistant biotype recovered from the foliar damage 1 to 2 wk after 2,4-D application, while the susceptible biotype was controlled. The production of H2O2 was responsive to temperature and increased more rapidly in the 2,4-D–resistant biotype than in the susceptible one at both 15 and 25 C; however, there was a greater increase at 25 C in the resistant biotype. H2O2 production was not light dependent in 2,4-D–resistant C. sumatrensis, with increases even under dark conditions. The 2,4-D–resistant biotype showed rapid photosynthetic damage, possibly due to the rapid necrosis and leaf disruption, and increased H2O2 content compared with the susceptible biotype.

Herbicide-resistant weed management is one of the greatest agricultural challenges in crop production. Thus, the quick identification of herbicide-resistant weeds is extremely important for management. This study aimed to evaluate resistance to PSI-inhibiting herbicides (diquat) and physiological response to paraquat application in Sumatran fleabane [Conyza sumatrensis (Retz.) E. Walker; syn.: Erigeron sumatrensis Retz.]. The research was conducted with two C. sumatrensis biotypes, one susceptible and the other with multiple resistance to herbicides from five different modes of action (glyphosate, paraquat, diuron, saflufenacil, and 2,4-D). A dose–response assay was carried out to evaluate herbicide resistance to diquat in the paraquat-resistant C. sumatrensis biotype. The enzymatic activities of superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX), hydrogen peroxide (H2O2) content, and chlorophyll a (Chl a) fluorescence were measured in both biotypes after paraquat (400 g ai ha−1) application. The dose–response assay confirmed resistance of C. sumatrensis to diquat with resistance factor levels of 26-fold and 6-fold for LD50 and GR50 values, respectively, compared with the susceptible biotype. Accumulation of H2O2 occurred more rapidly in the paraquat-susceptible biotype than in the resistant one. Paraquat treatment caused an increase in SOD and APX activity in the susceptible biotype, but antioxidant enzyme activities were unaffected by paraquat in the resistant one at 5 h after application (HAA). Chl a fluorescence increased across the first 4 HAA in both resistant and susceptible biotypes. However, at 24 HAA, the resistant biotype showed a decline in fluorescence close to untreated plants, while the susceptible biotype died, confirming resistance to diquat in the paraquat-resistant C. sumatrensis biotype. The paraquat-resistant biotype does not induce antioxidative enzymes, as a possible mechanism of resistance to paraquat, but shows rapid recovery of photosynthesis and continuous growth when subjected to paraquat, while the paraquat-susceptible biotype does not survive.

Few proteins have come under such intense scrutiny as superoxide dismutase-1 (SOD1). For almost a century, scientists have dissected its form, function and then later its malfunction in the neurodegenerative disease amyotrophic lateral sclerosis (ALS). We now know SOD1 is a zinc and copper metalloenzyme that clears superoxide as part of our antioxidant defence and respiratory regulation systems. The possibility of reduced structural integrity was suggested by the first crystal structures of human SOD1 even before deleterious mutations in the sod1 gene were linked to the ALS. This concept evolved in the intervening years as an impressive array of biophysical studies examined the characteristics of mutant SOD1 in great detail. We now recognise how ALS-related mutations perturb the SOD1 maturation processes, reduce its ability to fold and reduce its thermal stability and half-life. Mutant SOD1 is therefore predisposed to monomerisation, non-canonical self-interactions, the formation of small misfolded oligomers and ultimately accumulation in the tell-tale insoluble inclusions found within the neurons of ALS patients. We have also seen that several post-translational modifications could push wild-type SOD1 down this toxic pathway. Recently we have come to view ALS as a prion-like disease where both the symptoms, and indeed SOD1 misfolding itself, are transmitted to neighbouring cells. This raises the possibility of intervention after the initial disease presentation. Several small-molecule and biologic-based strategies have been devised which directly target the SOD1 molecule to change the behaviour thought to be responsible for ALS. Here we provide a comprehensive review of the many biophysical advances that sculpted our view of SOD1 biology and the recent work that aims to apply this knowledge for therapeutic outcomes in ALS.

Rats with a normal birth weight (NBW) or intra-uterine growth retardation (IUGR) were fed basic diets (NBW and IUGR groups) or basic diets supplemented with curcumin (NC and IC groups) from 6 to 12 weeks. The body weight of IUGR rats was lower (P<0·05) than that of the controls. Rats with IUGR showed higher (P<0·05) concentrations of TNF-α, IL-1β and IL-6; higher (P<0·05) activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in their serum; and increased (P<0·05) concentrations of malondialdehyde (MDA), protein carbonyl (PC) and 8-hydroxy-2'-deoxyguanosine (8-OHDG) in the liver compared with the NBW rats. The livers of IUGR rats exhibited a lower (P<0·05) superoxide dismutase activity and decreased (P<0·05) metabolic efficiency of the hepatic glutathione redox cycle compared with those of the NBW rats. In response to dietary curcumin supplementation, concentrations of inflammatory cytokines and activities of AST and ALT in the serum and MDA, PC and 8-OHDG in the liver were lower (P<0·05), and the hepatic glutathione redox cycle in the liver was improved (P<0·05) in the IC group than in the IUGR group. These results were associated with lower (P<0·05) phosphorylated levels of the NF-κB pathway and Janus kinase 2 (JAK2) and higher (P<0·05) mRNA expression of genes involved in the nuclear factor, erythroid 2-like 2 (Nfe2l2)/antioxidant response element (ARE) pathway in the liver of the IC rats than that of the IUGR rats. Maternal undernutrition decreased birth weight and led to inflammation, oxidative damage and injury in rats. Curcumin appeared to be beneficial in preventing IUGR-induced inflammation, oxidative damage and injury by activating the expression of the NF-κB, JAK/STAT and Nfe2l2/ARE pathways in the liver.

Coenzyme Q10 (Q10) plays an important role in the cellular antioxidant system by protecting the cells from free-radical oxidative damage and apoptosis. In the present study, we have investigated the effect of Q10 on the preimplantation development of porcine parthenogenetic embryos, as well as the underlying mechanism. The results showed that 100 μM was the optimal concentration of Q10, which resulted in significantly increased cleavage and blastocyst formation rates and improvement of blastocyst quality. Q10 improved the blastocyst hatching rate and cellular proliferation rate in hatching blastocysts and increased the expression of hatching-related genes. Furthermore, Q10 not only decreased reactive oxygen species production, DNA damage levels, and apoptosis in the blastocysts from H2O2-induced oxidative injury, but also maintained mitochondrial function. Taken together, these results indicate that Q10 has beneficial effects on the development of porcine parthenogenetic embryos by preventing oxidative damage and apoptosis.

Propolis is a resinous hive product collected by honeybees from various sources of plants. Numerous scientific investigations have been focused on the biological activities of propolis and its functions as a health supplement in humans. It could have similar function in other animals, such as in poultry. This review is focused on the recent findings concerning the effects of propolis, as an antioxidant, on performance, carcass characteristics, behaviour, immunity, and physiological homeostasis in domesticated poultry species (broiler chickens, laying hens, quail, and duck); and the needs in future poultry research.

The relationship between hydrophobicity and the protective effect of whey protein hydrolysates (WPHs) against oxidative stress was studied. Whey protein was first hydrolysed by pepsin and trypsin to obtain WPHs. After absorbed by macroporous adsorption resin DA201-C, three fractions named as M20, M40, and M60 were eluted by various concentrations of ethanol. The hydrophobicity showed a trend of increase from M20 to M60. Antioxidant ability test in vitro indicated that all the three components of WPHs displayed reasonably good antioxidant ability. Moreover, with the increase of hydrophobicity, antioxidant ability of WPHs improved significantly. Then rat pheochromocytoma line 12 (PC12) cells oxidative model was built to evaluate the suppression of oxidative stress of three components on PC12 cells induced by H2O2. Morphological alterations, cell viability, apoptosis rate, and intracellular antioxidase system tests all indicated that WPHs exert significant protection on PC cells against H2O2-induced damage. Among them, M60 had the highest protective effect by increasing 19·3% cell survival and reducing 28·6% cell apoptosis. These results suggested hydrophobicity of WPHs was contributing to the antioxidant ability and the protective effect against oxidative damage.

Treatment with a combination of four nutrients, i.e. R-α-lipoic acid, acetyl-l-carnitine, nicotinamide and biotin, just as with pioglitazone, significantly improves glucose tolerance, insulin release, plasma NEFA, skeletal muscle mitochondrial biogenesis and oxidative stress in Goto–Kakizaki (GK) rats. However, it is not known whether treatment with these nutrients can improve mitochondrial function and reduce oxidative stress in GK rats. The effects of a combination of these four nutrients on mitochondrial function, oxidative stress and apoptosis in GK rat liver were investigated. Livers of untreated GK rats showed (1) abnormal changes in the activities of mitochondrial complexes (decreases in I, III and IV and increases in II and V), (2) increases in protein oxidation, (3) decreases in antioxidant enzymes (superoxide dismutase, glutathione S-transferase, NADH-quinone oxidoreductase-1), (4) a decrease in total antioxidant capacity but increases in reduced glutathione level and glyceraldehyde 3-phosphate dehydrogenase expression and (5) significant increases in apoptosis biomarkers, including expression of p21 and p53. A 3-month treatment with the four nutrients significantly improved most of these abnormalities in GK rats, and the effects of the nutrient combination were greater than those of pioglitazone for most of these indices. These results suggest that dietary supplementation with nutrients that are thought to influence mitochondrial function may be an effective strategy for improving liver dysfunction in GK diabetic rats.

Dioxins are lipophilic compounds with a small molecular weight and are highly persistent, bioaccumulative and toxic. Dioxin detoxification is associated with an increased production of reactive oxygen species (ROS). In physiological conditions the body is protected against ROS and their toxic products by a wide range of antioxidant systems. We hypothesize that the imbalance between ROS production, associated with dioxin exposure, and the antioxidant defence capacity, may lead to oxidative stress, with consequent increased consumption of antioxidants and accumulation of toxic compounds in blood and tissues. The objective of this study was to evaluate the effect of exposure to dioxins on the plasma redox status of lactating buffalo cows. To this aim, the major liposoluble (retinol and α-tocopherol) and water-soluble (ascorbate) antioxidants, the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity, the total antioxidant capacity (TAC), as well as specific protein oxidation markers (protein bound carbonyls and nitro-tyrosine) and lipid oxidation markers (hydroperoxides), were chosen as indices of blood redox status. The concentration of antioxidants, protein-bound carbonyls (PC), nitro-tyrosine (N-Tyr), and hydroperoxides (LPO), the SOD and GPx activity, and the TAC were measured in plasma samples obtained from buffalo cows exposed to environmental levels of dioxins higher (n=21, group A) or lower (n=29; group B) than those permitted. Plasma titres of antioxidants, as measured by HPLC, and the total antioxidant capacity, as measured by trolox equivalents capacity, were higher in group B than in A. Similarly, SOD and GPx activities were higher in group B than in A. Conversely, plasma levels of PC, N-Tyr and LPO, as measured by ELISA, were higher in group A than in B. Our results suggest that exposure to dioxins impairs the plasma antioxidant defence system of lactating buffalo cows, and that metabolic processes associated with dioxin detoxification might induce or enhance oxidation of protein and lipids. This adverse effect on blood redox status might have negative implications for animal health and reproduction, and might compromise animal welfare.

The aim of the present study was to verify whether extra-virgin olive oil, a dietary component naturally containing phenolic antioxidants, has the potential to protect the brain from the deleterious effects of ageing. To accomplish this goal, we used male rats fed a high-energy diet containing either maize oil, or extra-virgin olive oil with high or low phenol content (720 or 10 mg total phenols/kg oil, corresponding to a daily dose of 4 or 0·05 mg total phenols/kg body weight, respectively) from age 12 months to senescence. The measured endpoints were biochemical parameters related to oxidative stress and functional tests to evaluate motor, cognitive and emotional behaviour. Olive oil phenols did not exert major protective actions on motor and cognitive function, as we observed only a tendency to improved motor coordination on the rotarod in the old animals treated with the oil rich in phenols (40 % average increase in the time to first fall; P = 0·18). However, an interesting finding of the present study was a reduced step-through latency in the light–dark box test, found in the older animals upon treatment with the oil rich in antioxidant phenols, possibly indicating an anxiety-lowering effect. This effect was associated with decreased glutathione reductase activity and expression in the brain, a phenomenon previously associated with decreased anxiety in rodents. These results indicate a previously undetected effect of a diet containing an olive oil rich in phenols. Further studies are warranted to verify whether specific food antioxidants might also have an effect on emotional behaviour.

Space flight is a new experience for man. Tension on the weight-bearing components of the musculo–skeletal system is greatly reduced, as is the work required for movement. The body responds by a reductive remodelling of the musculo–skeletal system. Protein is lost from muscles with anti-gravity functions. The rate of Ca loss from the weight-bearing bones is about 1 % per month. Voluntary dietary intake is reduced during space flight by about 20 %. These adaptations to weightlessness leave astronauts ill-equipped for life with gravity when they return to earth. Rates of energy expenditure are similar to that expected on the ground for comparable activities. Protein intake is adequate in flight but may be limiting after space flight due to substrate competition between repleting muscle and other anabolic processes. The most serious nutritional problem is the inability to maintain energy balance on missions with high exercise requirements. The poor dietary intake is probably a consequence of engineering-imposed environmental constraints. The low levels of lighting in the space vehicle may not be enough to promote vitamin D synthesis. Nevertheless, the evidence suggests that a normal well-balanced diet with plenty of fluids will be as healthy in space as on earth. The long-term goal of the manned space programme is to develop the means of sustaining human life beyond earth. This will involve the development of technologies to grow food, maintain a breathable atmosphere and recycle waste products with the only external input being energy.

Evidence from biochemical and animal models suggests that nutritional antioxidants should inhibit the development of diseases such as CHD and certain cancers. This evidence is not clearly corroborated by intervention studies in human subjects, due, in part, to inadequacies in current analytical methodologies. Although in vitro assays can give useful information on the attributes required by a compound to act as an antioxidant, results may have little nutritional relevance due to limited bioavailability. The determination of antioxidants in blood is often used as a measure of antioxidant status in vivo, but may not necessarily reflect concentrations in target tissues where oxidative stress is greatest. In addition, the accumulation of antioxidants in selective tissues may not be apparent from plasma measurements. Participation in quality-control schemes for antioxidant determination by HPLC allows inter-laboratory comparison of results. Moderation of indices of oxidative damage to lipids, proteins and DNA can provide information on the effectiveness of compounds as nutritional antioxidants. However, most current methods of assessing oxidative stress are subject to confounding factors of non-oxidative origin. Assays for total antioxidant capacity in plasma differ in their type of oxidation source, target and measurement used to detect the oxidized product. They give different results, should never be used in isolation, and results should be interpreted with caution. Until more is known about the activity and metabolic fate of antioxidants, caution should be exercised in the consumption of large amounts of commercially-available antioxidant preparations.

A high dietary fat intake and low physical activity characterize the current Western lifestyle. Dietary fatty acids do not stimulate their own oxidation and a surplus of fat is stored in white adipose tissue, liver, heart and muscle. In these organs intracellular lipids serve as a rapidly-available energy source during, for example, physical activity. However, under conditions of elevated plasma fatty acid levels and high dietary fat intake, conditions implicated in the development of modern diseases such as obesity and type 2 diabetes mellitus, fat accumulation in liver and muscle (intramyocellular lipids; IMCL) is associated with the development of insulin resistance. Recent data suggest that IMCL are specifically harmful when combined with reduced mitochondrial function, both conditions that characterize type 2 diabetes. In the (pre)diabetic state reduced expression of the transcription factor PPARγ co-activator-1α (PGC-1α), which is involved in mitochondrial biogenesis, has been suggested to underlie the reduced mitochondrial function. Importantly, the reduction in PGC-1α may be a result of low physical activity, consumption of high-fat diets and high plasma fatty acid levels. Mitochondrial function can also be impaired as a result of enhanced mitochondrial damage by reactive oxygen species. Fatty acids in the vicinity of mitochondria are particularly prone to lipid peroxidation. In turn, lipid peroxides can induce oxidative damage to mitochondrial RNA, DNA and proteins. The mitochondrial protein uncoupling protein 3, which is induced under high-fat conditions, may serve to protect mitochondria against lipid-induced oxidative damage, but is reduced in the prediabetic state. Thus, muscular lipotoxicity may impair mitochondrial function and may be central to insulin resistance and type 2 diabetes mellitus.

Embryonic axes of tea (desiccation sensitive) and pea (desiccation tolerant) were dried at different rates or stored at different water contents to distinguish between damage associated with the immediate effects of water loss and the longer-term effects of a partially hydrated state. No loss of viability was observed if pea axes were dried sufficiently rapidly (from 1.8 to 0.1 g H2O g-1dry mass (g/g) within 5 d). However, viability was lost in tea axes dried below 0.5 g/g (approximately -15 MPa) even if axes were dried within 1 h. Death in tea axes dried to moisture contents less than 0.5 g/g probably resulted from the removal of water necessary for cellular structural integrity (i.e. desiccation damage sensu stricto). When axes of both species were dried at slower rates, viability losses were observed at water potentials between about -3 and -15 MPa. The timing for this type of damage was species dependent, occurring within 2 d for tea and after 5 d for pea, and may be explained by higher oxidative activity in tea compared to pea. Embryos of both species with water potentials below -3 MPa were lethally damaged if oxygen consumption exceeded 1000–5000 μmol O2 g-1dry mass. Recalcitrant seeds are different than orthodox seeds because the former do not survive drying below a critical water content, regardless of the drying rate. Rapid drying is required for accurate assessment of the critical water content. Slow drying leads to metabolic imbalance and artefactual assessment of the critical water content for desiccation damage. Both tea and pea seeds were susceptible to damage from metabolic imbalances, suggesting that the predominant stress from slow drying is ageing.

A diet rich in fruits, vegetables and minimally refined cereals is associated with lower risk for chronic degenerative diseases. Since oxidative stress is common in chronic degenerative disease, it has been assumed that dietary antioxidants may explain this protective effect. Every dietary plant contains numerous types of antioxidants with different properties. Many of these antioxidants cooperate in oxidative stress reduction in plants, and we hypothesize that many different antioxidants may also be needed for the proper protection of animal cells. To test this hypothesis, it is useful to identify dietary plants with high total antioxidant content. Several nuts are among the dietary plants with the highest content of total antioxidants. Of the tree nuts, walnuts, pecans and chestnuts have the highest contents of antioxidants. Walnuts contain more than 20 mmol antioxidants per 100 g, mostly in the walnut pellicles. Peanuts (a legume) also contribute significantly to dietary intake of antioxidants. These data are in accordance with our present extended analysis of an earlier report on nut intake and death attributed to various diseases in the Iowa Women's Health Study. We observed that the hazard ratio for total death rates showed a U-shaped association with nut/peanut butter consumption. Hazard ratio was 0·89 (CI =0·81–0·97) and 0·81 (CI =0·75–0·88) for nut/peanut butter intake once per week and 1–4 times per week, respectively. Death attributed to cardiovascular and coronary heart diseases showed strong and consistent reductions with increasing nut/peanut butter consumption. Further studies are needed to clarify whether antioxidants contribute to this apparent beneficial health effect of nuts.

Numerous theories of ageing have been proposed, and many have been tested experimentally, particularly using nematode models such as Caenorhabditis elegans. By combining those theories of ageing that remain plausible with recent findings from studies of C. elegans life span mutants, an integrated theory of ageing has been devised. This is formed from 3 interconnected elements: the evolutionary theory of ageing, the oxidative damage theory of ageing, and a nonadaptive programmed ageing theory. This tripartite theory of ageing gives rise to a number of predictions that may be tested experimentally.

We examined the effects of high-fructose (FR) feeding on the development of diabetic complications in the lens and the kidney of streptozotocin (STZ)-diabetic rats. Male Wistar Furth rats were treated with one of two doses of STZ (HIGH STZ, 55 mg/kg body weight; MOD STZ, 35 mg/kg body weight) or vehicle alone (SHAM) and were then assigned to a control (CNTL) or 400 g FR/kg diet for 12 weeks. At the end of the study, body weight, plasma glucose and insulin concentrations differed among STZ groups (HIGH v. MOD v. SHAM, P<0·001) but did not differ due to diet. Plasma FR concentrations were significantly higher in FR-fed v. CNTL-fed groups (P<0·0001) and in HIGH-STZ groups v. MOD-STZ and SHAM groups (P<0·0004 and P<0·0001 respectively). Focal length variability of the lens, a quantitative measure of cataract formation, was increased in the HIGH STZ, FR group compared with the HIGH STZ, CNTL group (P<0·01). The concentration of H2O2 in kidney microsomes was significantly higher in HIGH STZ, FR rats v. HIGH STZ, CNTL rats (P<0·01). Microalbuminuria was not observed in any of the groups examined, and there was no evidence of extensive histological damage in the kidney from any rats. Under conditions of severe hyperglycaemia, high FR intake promotes the development of cataracts in the lens of the eye, and results in increased concentrations of substances indicative of oxidative stress in the kidney. Although FR has been suggested as a carbohydrate source for diabetics, a high FR diet coupled with hyperglycaemia produces effects that may promote some of the complications associated with diabetes.