Oxidative stress in growth hormone transgenic coho salmon with compressed lifespan – a model for addressing aging

Abstract

Growth hormone (GH) transgenic fish have dramatically enhanced growth rates, increased oxygen demands and reactive oxygen species production. GH-transgenic coho salmon provide an opportunity to address effects of increased metabolism on physiological aging. The objective of this study was to compare oxidative stress in wild-type (WT) and GH-transgenic (T) coho salmon (Oncorhynchus kisutch) of different ages (1 and 2 years). Antioxidant enzyme activity, protein carbonyls (PC) and glutathione (GSH, GSSG) were measured. PC correlated to growth rates in individual fish. T fish exhibited lower antioxidant enzyme activities and GSH levels compared to the WT, while levels of PC and GSSG were higher. Age affects were observed in both WT and T fish; enzyme activities and GSH decreased while PC and GSSG increased. Our results support the metabolic rate theory of aging. This study aims to be a platform for continued studies of the theories of aging using fish as model organisms.     

Role of Magnesium in Oxidative Stress in Individuals with Obesity

Adipose tissue is considered an endocrine organ that promotes excessive production of reactive oxygen species when in excess, thus contributing to lipid peroxidation. Magnesium deficiency contributes to the development of oxidative stress in obese individuals, as this mineral plays a role as an antioxidant, participates as a cofactor of several enzymes, maintains cell membrane stability and mitigates the effects of oxidative stress. The objective of this review is to bring together updated information on the participation of magnesium in the oxidative stress present in obesity. We conducted a search of articles published in the PubMed, SciELO and LILACS databases, using the keywords ‘magnesium’, ‘oxidative stress’, ‘malondialdehyde’, ‘superoxide dismutase’, ‘glutathione peroxidase’, ‘reactive oxygen species’, ‘inflammation’ and ‘obesity’. The studies show that obese subjects have low serum concentrations of magnesium, as well as high concentrations of oxidative stress marker in these individuals. Furthermore, it is evident that the adequate intake of magnesium contributes to its appropriate homeostasis in the body. Thus, this review of current research can help define the need for intervention with supplementation of this mineral for the prevention and treatment of disorders associated with this chronic disease.     

Patient-derived fibroblasts indicate oxidative stress status and may justify antioxidant therapy in OXPHOS disorders

Oxidative phosphorylation disorders are often associated with increased oxidative stress and antioxidant therapy is frequently given as treatment. However, the role of oxidative stress in oxidative phosphorylation disorders or patients is far from clear and consequently the preventive or therapeutic effect of antioxidants is highly anecdotic. Therefore, we performed a systematic study of a panel of oxidative stress parameters (reactive oxygen species levels, damage and defense) in fibroblasts of twelve well-characterized oxidative phosphorylation patients with a defect in the POLG1 gene, in the mitochondrial DNA-encoded tRNA-Leu gene (m.3243A>G or m.3302A>G) and in one of the mitochondrial DNA-encoded NADH dehydrogenase complex I (CI) subunits. All except two cell lines (one POLG1 and one tRNA-Leu) showed increased reactive oxygen species levels compared with controls, but only four (two CI and two tRNA-Leu) cell lines provided evidence for increased oxidative protein damage. The absence of a correlation between reactive oxygen species levels and oxidative protein damage implies differences in damage prevention or correction. This was investigated by gene expression studies, which showed adaptive and compensating changes involving antioxidants and the unfolded protein response, especially in the POLG1 group. This study indicated that patients display individual responses and that detailed analysis of fibroblasts enables the identification of patients that potentially benefit from antioxidant therapy. Furthermore, the fibroblast model can also be used to search for and test novel, more specific antioxidants or explore ways to stimulate compensatory mechanisms.     

Investigation of Cadmium-Induced Genotoxicity and Oxidative Stress Response in Indian Major Carp,Labeo rohita

We investigated genotoxicity and oxidative stress in the gills of Labeo rohita exposed to 33.6, 67.1, and 100.6 mg L^–1of cadmium chloride at 96 h. Genotoxicity was assessed using single cell gel electrophoresis whereas oxidative stress was monitored through lipid peroxidation induction and antioxidant response parameters, namely reduced glutathione (GSH), glutathione peroxidase, glutathione-S-transferase, superoxide dismutase, and catalase (CAT) activities. Significant (p < .05) effect of both concentration and time of exposure was observed on the extent of DNA damage in treated fish. Similarly, malondialdehyde content, level of GSH, and activities of antioxidant enzymes were significantly elevated in treated groups, except CAT. The increased DNA damage and lipid peroxidation (LPO) content along with fluctuation in antioxidant defense system in fish indicated the interaction of cadmium (Cd) with DNA repair processes and production of reactive oxygen species. Thus, Cd is liable for induction of LPO, alteration of antioxidant defenses, and DNA damage in gills of L. rohita.     

Effects of different environmental oxygen levels on free radical processes in fish

Changes in oxygen levels occur frequently in aquatic environments; therefore, water organisms, including fishes, evolve a wide spectrum of adaptations to both anoxia/hypoxia and hyperoxia. The review describes oxidative damage to cellular constituents by reactive oxygen species, alterations in glutathione status, and response of antioxidant enzymes to variable oxygen availability in fish. Anoxia- and hypoxia-tolerant species demonstrate an anticipatory increase of some antioxidant enzymes during low-oxygen state in order to enhance their antioxidant potential for dealing with possible oxidative stress upon return to normoxia. Under hyperoxic conditions, it seems that the glutathione system plays an important adaptive role. Most stressful conditions lead to a quick increase in lipid peroxidation products that, in turn, are detoxified rapidly by respective low- and high-molecular weight antioxidants. A scheme on possible ways of regulating antioxidant enzymes by different oxygen levels is proposed.     

Oxidative stress in biological systems and its relation with pathophysiological functions: the effect of physical activity on cellular redox homeostasis

The body of evidence from the past three decades demonstrates that oxidative stress can be involved in several diseases. This study aims to summarise the current state of knowledge on the association between oxidative stress and the pathogenesis of some characteristic to the biological systems diseases and aging process. This review also presents the effect of physical activity on redox homeostasis. There is strong evidence from studies for participation of reactive oxygen and nitrogen species in pathogenesis of acute and chronic diseases based on animal models and human studies. Elevated levels of pro-oxidants and various markers of the oxidative stress and cells and tissues damage linked with pathogenesis of cancer, atherosclerosis, neurodegenerative diseases hypertension, diabetes mellitus, cardiovascular disease, atherosclerosis, reproductive system diseases, and aging were reported. Evidence confirmed that inflammation contributes widely to multiple chronic diseases and is closely linked with oxidative stress. Regular moderate physical activity regulates oxidative stress enhancing cellular antioxidant defence mechanisms, whereas acute exercise not preceded by training can alter cellular redox homeostasis towards higher level of oxidative stress. Future studies are needed to clarify the multifaceted effects of reactive oxygen/nitrogen species on cells and tissues and to continue study on the biochemical roles of antioxidants and physical activity in prevention of oxidative stress-related tissue injury.     

Social dominance does not increase oxidative stress in a female dominance hierarchy of an African cichlid fish

In many group living animal species, individuals use aggression to gain and maintain social dominance to secure access to ecological resources and potential mates. While social dominance has many fitness benefits, there are also potential costs associated with frequent agonistic interactions and status display. One potential cost of social dominance is oxidative stress, the imbalance of reactive oxygen species and antioxidant capacity. In the cichlid species Astatotilapia burtoni, dominant males are aggressive, hold a breeding territory, and have an activated reproductive system resulting in larger gonads. Subordinate males are submissive, school with females, and are nonreproductive. Females are submissive under natural conditions, but in a female-only group, a dominance hierarchy will form with dominant females taking on male-typical behaviours including aggression, territory defence, and increased androgen levels. However, in contrast to males, social dominance is not linked to increased activation of the reproductive system in females, allowing us to test whether social dominance alone exposes individuals to increased oxidative stress. We compared dominant and subordinate females in female-only groups in five markers of oxidative stress. Dominant females did not have higher levels of oxidative damage compared to same-sex subordinates. This result contrasted to the trend in males in which dominant males had higher oxidative damage than their subordinate counterparts. Our findings suggest that the oxidative cost of social dominance is limited and support the notion that previously reported associations between high rank and increased oxidative stress is most likely driven by increased investment in reproduction.     

Wheat variety carrying 2NvS chromosomal segment provides yield advantage through lowering terminal heat–induced oxidative stress

A 2N^vS chromosomal segment carrying bread wheat variety, BARI Gom 33 (‘BG33’), showed tolerance to terminal heat stress and higher yield over a heat-tolerant non-2N^vS BARI Gom 26 (‘BG26’) and a heat-susceptible Pavon 76 (‘Pavon’). This study aimed to ascertain the potential of the 2N^vS ‘BG33’ in terminal heat-induced oxidative stress tolerance compared to non-2N^vS ‘BG26’ and heat-susceptible ‘Pavon’ under two heat regimes at the reproductive stages viz. control (optimum sowing time) and heat stress (late sowing). We found that both ‘BG26’ and ‘BG33’ showed significantly higher tolerance to oxidative stress by limiting the generation of reactive oxygen species (ROS), methylglyoxal under heat stress. During terminal heat stress, both ‘BG33’ and ‘BG26’ exhibited greater cellular homeostasis than heat-susceptible ‘Pavon’, which was maintained by the increased accumulation of osmolytes, nonenzymatic antioxidants, and enzymes associated with ROS scavenging, ascorbate–glutathione cycle, and glyoxalase system. Lesser cellular damage in ‘BG26’ and ‘BG33’ was eventually imitated in a smaller reduction in grain yield (15 and 12%, respectively) than in ‘Pavon’, which had a 33% reduction owing to heat stress. Collectively, our findings revealed that the chromosomal segment 2N^vS provides yield advantage to ‘BG33’ under terminal heat stress by lowering oxidative damage. As 2N^vS translocation contains multiple nucleotide-binding domain leucine-rich repeat containing, cytochrome P450, and other gene families associated with plant stress tolerance, further studies are warranted to dissect the underlying molecular mechanisms associated with higher heat stress tolerance of 2N^vS carrying ‘BG33’.

     

Low oxygen tension alleviates oxidative damage and delays cellular senescence in G6PD-deficient cells

Previous studies have shown that glucose-6-phosphate dehydrogenase (G6PD)-deficient cells are under increased oxidative stress and undergo premature cellular senescence. The present study demonstrates that G6PD-deficient cells cultured under 3% oxygen concentration had an extended replicative lifespan, as compared with those cultured under atmospheric oxygen level. This was accompanied by a reduction in the number of senescence-associated β-galactosidase (SA-β-Gal) positive and morphologically senile cells at comparable population doubling levels (PDL). Concomitant with the extension of lifespan was decreased production of reactive oxygen species. Additionally, lifespan extension was paralleled by the greatly abated formation of such oxidative damage markers as 8-hydroxy-deoxyguanosine (8-OHdG) as well as the oxidized and cross-linked proteins. Moreover, the mitochondrial mass increased, but the mitochondrial membrane potential ΔΨm decreased in cells upon serial propagation. These changes were inhibited by lowering the oxygen tension. Our findings provide additional support to the notion that oxidative damage contributes to replicative senescence of G6PD-deficient cells and reduction of oxidative damage by lowering oxygen tension can delay the onset of cellular senescence.     

辛基酚胁迫对雄性泥鳅抗氧化酶及卵黄蛋白原的影响

为研究辛基酚(OP)对雄性泥鳅抗氧化酶活性及血清卵黄蛋白原(VTG)含量的影响,将雄性泥鳅分别暴露于4种不同质量浓度OP(0.12、0.19、0.32、0.52 mg/L)中持续7、14、21 d和28 d,采用试剂盒检测肝脏超氧化物歧化酶(SOD)与过氧化氢酶(CAT)的含量,采用碱不稳定性蛋白结合磷法检测血清VTG的含量。结果表明,0.12 mg/L OP胁迫14 d,肝脏SOD和CAT含量均无显著变化,但是随着胁迫剂量增大和时间延长,SOD和CAT含量降低极其显著,在0.52 mg/L OP胁迫28 d时降到最低水平;泥鳅在0.12 mg/L OP中暴露7 d时,血清VTG含量就有极其显著升高,且随着胁迫剂量增大和时间的延长,VTG含量呈升高趋势。提示OP胁迫对SOD和CAT活性有显著的抑制作用,并随胁迫剂量增大和时间延长而抑制加剧,造成氧化损伤;OP胁迫可诱导VTG合成,并随暴露剂量增大和时间延长而诱导增强,具有明显的雌激素效应,这可能与其氧化损伤有密切关系。     

Effects of seasonal and latitudinal cold on oxidative stress parameters and activation of hypoxia inducible factor (HIF-1) in zoarcid fish

Acute, short term cooling of North Sea eelpout Zoarces viviparus is associated with a reduction of tissue redox state and activation of hypoxia inducible factor (HIF-1) in the liver. The present study explores the response of HIF-1 to seasonal cold in Zoarces viviparus, and to latitudinal cold by comparing the eurythermal North Sea fish to stenothermal Antarctic eelpout (Pachycara brachycephalum). Hypoxic signalling (HIF-1 DNA binding activity) was studied in liver of summer and winter North Sea eelpout as well as of Antarctic eelpout at habitat temperature of 0°C and after long-term warming to 5°C. Biochemical parameters like tissue iron content, glutathione redox ratio, and oxidative stress indicators were analyzed to see whether the cellular redox state or reactive oxygen species formation and HIF activation in the fish correlate. HIF-1 DNA binding activity was significantly higher at cold temperature, both in the interspecific comparison, polar vs. temperate species, and when comparing winter and summer North Sea eelpout. Compared at the low acclimation temperatures (0°C for the polar and 6°C for the temperate eelpout) the polar fish showed lower levels of lipid peroxidation although the liver microsomal fraction turned out to be more susceptible to lipid radical formation. The level of radical scavenger, glutathione, was twofold higher in polar than in North Sea eelpout and also oxidised to over 50%. Under both conditions of cold exposure, latitudinal cold in the Antarctic and seasonal cold in the North Sea eelpout, the glutathione redox ratio was more oxidised when compared to the warmer condition. However, oxidative damage parameters (protein carbonyls and thiobarbituric acid reactive substances (TBARS) were elevated only during seasonal cold exposure in Z. viviparus. Obviously, Antarctic eelpout are keeping oxidative defence mechanisms high enough to avoid accumulation of oxidative damage products at low habitat temperature. The paper discusses how HIF could be instrumental in cold adaptation in fish.     

Detection of nodularin in European flounder (Platichthys flesus) in the west coast of Sweden: Evidence of nodularin mediated oxidative stress

The brackish, bloom-forming cyanobacterium Nodularia spumigena produces a peptide called nodularin, which may induce liver damage in fish. In the summer of 2007, nodularin was detected in liver tissue of European flounder caught in Swedish waters of Öresund, within the upper salinity limit for N. spumigena. Nodularin concentrations ranging between 22 and 557 μg kg⁻¹ liver (d.w.) were detected in fish liver. Nodularin was not detected in blue mussels (Mytilus edulis). Although N. spumigena blooms can occur in the area, the cyanobacteria were only present in very small amounts in 2007. Results suggested that nodularin accumulated in flounder livers during the summer of 2006, when vast N. spumigena blooms were observed in Öresund, and persisted over several months. Nodularin has previously been shown to induce oxidative stress in mice, crustaceans and mollusks but work on the potential negative effects of nodularin on fish is still scarce. To examine the dynamics of nodularin induced oxidative stress in liver tissue of flounder, the differential responses of the antioxidant enzymes glutathione-S-transferase catalase (CAT) and the formation of malondialdehyde (MDA) were monitored during 14 days in flounder exposed to an intraperitoneal injection of nodularin (0, 2, 10 and 50 μg nodularin kg⁻¹ body weight). The activities of GST and CAT in the liver decreased significantly in the 50 μg nodularin kg⁻¹ exposure after 7 days, but were restored to control levels after an additional 10 days of recovery. The results suggested that nodularin induced oxidative stress in terms of decreased GST and CAT activity, which can result in increased vulnerability of the cell to reactive oxygen species (ROS). No significant changes could be found in MDA levels between the treatments. Thus, the antioxidant defense system presumably managed to prevent oxygen mediated toxicity as seen by the unchanged levels of MDA. Alteration of the enzymatic defense system may increase energetic costs, thus reducing fish growth and survival. The present study also suggests that oxidative stress biomarkers can be used in fish to detect early responses to nodularin.     

Protective effects of fluvastatin against reactive oxygen species induced DNA damage and mutagenesis

Oxidative stress may be an important factor in the development of diabetic complications. Advanced glycation end-products have drown attention as potential sources of oxidative stress in diabetes. We investigated the protective effects of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on oxidative DNA damage from reactive oxygen species or advanced glycation end-products in vitro, as well as effects of main fluvastatin metabolites and other inhibitors of the same enzyme, pravastatin and simvastatin. Protective effects were assessed in terms of the DNA breakage rate in a single-stranded phage DNA system in vitro. DNA was exposed to either reactive oxygen species or advanced glycation end-products. Fluvastatin and its metabolites showed a strong protective effect comparable to those seen with thiourea and mannitol, though pravastatin and simvastatin did not exert clear protective effects. Furthermore, fluvastatin reduced the mutagenesis by reactive oxygen species or advanced glycation end-products in Salmonella typhimurium test strains. Both pravastatin and simvastatin still lacked protective activity. Fluvastatin and its metabolites protect against oxidative DNA damage and may reduce risk of consequent diabetic complications.     

The effects of radiation on sperm swimming behavior depend on plasma oxidative status in the barn swallow (Hirundo rustica)

Sperm are highly susceptible to reactive oxygen species (ROS) that can damage sperm DNA and structure, resulting in reduced fertilizing capacity. Exposure to radioactive contamination can also impair sperm swimming behavior and fertilizing ability, both through a reduction of sperm DNA integrity and via an increased generation of reactive oxygen species (ROS). However, the relationship between individual oxidative status and sperm swimming behavior has never been investigated in any wild population of animals exposed to radioactive contamination. We studied the motility of sperm collected from barn swallows, Hirundo rustica, breeding under different levels of radioactive contamination following the Chernobyl accident in 1986, in relation to individual oxidative status. We tested the hypothesis that the degree of impairment of sperm swimming behavior by radioactive contamination depended on plasma antioxidant capacity, the level of reactive oxygen metabolites (ROMs) and oxidative stress (sensu Costantini et al. 2006), a better oxidative status being associated with higher sperm motility. Sperm behavior parameters were subjected to principal component (PC) analysis, which extracted four PCs explaining 86% of the variance in sperm motility. PC2, representing sperm with high track velocity and ample lateral head displacement, was significantly predicted by the interaction between radiation level and either oxidative damage or oxidative stress. Contrary to our predictions, the highest values of PC2 were associated with relatively high radiation levels, particularly for high levels of either ROMs or oxidative stress. In addition, there was a tendency for values of PC3 (representing the percent of motile sperm) and PC4 (representing slow sperm with high beat cross frequency) to depend on the interaction between radiation level and total plasma antioxidant protection. Our results confirm the importance of oxidative status in determining the genetic and physiological outcome of exposure to radioactive contamination, complementing previous studies relating sperm abnormality to circulating levels of specific antioxidants. Our results also complement previous evidence that oxidative damage of sperm was negatively related to sperm motility, thus indicating a possible trade-off in quenching pro-oxidant compounds in the plasma and the seminal fluid.     

Effects of a bout of traditional and original sumo training on neutrophil immune function in amateur university sumo wrestlers

In order to examine in detail the influence on the neutrophil immune function in sumo wrestlers of performing traditional and original training we examined changes in the neutrophil immune function in 17 male amateur university sumo wrestlers (aged 20.2 ± 1.5 years), before (‘Pre’) and after the training (‘Post’) for 2.5 h under fasting conditions. Assays included blood leukocyte and neutrophil counts, serum concentration of immunoglobulins, complements, myogenic enzymes and neutrophil oxidative burst activity (OBA) and phagocytic activity (PA). Myogenic enzymes, neutrophil counts, the ratio of neutrophil counts:leukocyte counts significantly increased and immunoglobulins and complements decreased in Post compared with Pre. There was a positive correlation between the change of neutrophil counts before and after the training and the change of creatine kinase (r = 0.667, p < 0.01). The Post OBA significantly increased and PA significantly decreased compared with Pre. It was concluded that sumo training causes muscular damage and an increase in the neutrophil count as a response. In this time, although OBA increased, PA decreased after training. Compensation between PA and reactive oxygen species production may exist to maintain the overall integrity of the neutrophil immune function. Copyright © 2008 John Wiley & Sons, Ltd.     

Effect of drought and rewatering on the cellular status and antioxidant response of Medicago truncatula plants

Effects of water stress on plants have been well-documented. However, the combined responses to drought and rewatering and their underlying mechanisms are relatively unknown. The present study attempts to describe spatiotemporal alterations in the physiology and cellular status of Medicago truncatula tissues that result from and subsequently follow a period of moderate water deficit. Physiological processes and cellular damage levels were monitored in roots and leaves by determining lipid peroxidation levels, as well as nitric oxide and hydrogen peroxide content, further supported by stomatal conductance and chlorophyll fluorescence measurements in leaves. During water stress, cells in both organs displayed increased damage levels and reactive oxygen and nitrogen species content, while leaves showed reduced stomatal conductance. Furthermore, both tissues demonstrated increased proline content. Upon rewatering, plants recovered displaying readings similar to pre-stress control conditions. Furthermore, molecular analysis of antioxidant gene expression by quantitative real-time RT-PCR revealed differential spatiotemporal regulation in a number of genes examined (including catalase, cytosolic ascorbate peroxidase, copper/zinc and iron superoxide dismutase and alternative oxidase). Overall, M. truncatula plants demonstrated increased sensitivity to drought-induced oxidative damage; however, this was reversed following rewatering indicating a great elasticity in the plant''s capacity to cope with free oxygen and nitrogen radicals.Key words: drought stress, antioxidants, cellular damage, medicago, proline, hydrogen peroxide, nitric oxide, reactive oxygen species, reactive nitrogen species     

干旱与氧化胁迫对小麦根氧化还原状态和叶片ABA积累的影响

通过分析一氧化氮(nitric oxide,NO)、活性氧(reactive oxygen species,ROS)和干旱胁迫对小麦根氧化还原状态和叶片脱落酸(abscisic acid,ABA)积累的影响,探讨了干旱胁迫下NO和H2O2调节ABA合成的可能机制。结果表明:干旱胁迫处理初期小麦根还原型谷胱甘肽含量降低、抗氧化酶活性发生振荡变化,细胞氧化还原状态向氧化型转变。NO和H2O2能模拟干旱胁迫的作用使细胞状态向氧化型转变,还可以使小麦叶片ABA积累量上升。干旱胁迫下NO和H2O2对ABA合成的调节作用可能是通过调节细胞氧化还原状态进行。     

Oxidative damage markers and inflammatory cytokines are altered in patients suffering with post-chikungunya persisting polyarthralgia

Redox homoeostasis is necessary for the maintenance of living systems. Chikungunya viral infection manifests into joint inflammation and debilitating polyarthralgia affecting the life style of the patient badly. The disease pathophysiology is poorly understood and there is a lack of targeted therapeutics. The pathogenic role of free radicals in arthritis is well established. This study aims for the first time to evaluate the status of several standard oxidative stress markers and their correlation in chikungunya patients suffering with polyarthralgia. Expression of Siglec-9 on monocytes; which can modulate oxidative stress is studied along with intracellular reactive oxygen species (ROS), cellular lipid and protein damage markers in chikungunya patients with/without persisting polyarthralgia along with healthy controls. Furthermore, plasma NO level, antioxidant status was investigated along with some inflammatory cytokines namely IL-6, IFN-γ, CXCL-9, IL-10 and TGFβ1. Interestingly, all oxidative damage markers are altered significantly in groups but their alteration levels vary in patients with/without persisting polyarthralgia. Siglec-9 expression level is increased in patients revealing cellular response to manage oxidative stress with respect to controls. Correlation studies reveal that intracellular ROS correlates well with most of the studied parameters but the correlation coefficient (Pearson r) differs with disease manifestation demonstrating strong role of these factors in a pro-oxidant milieu. The presence of free radicals increases the availability of neoantigens continuously, which possibly further cascades oxidative damage and development of persisting polyarthralgia.