Differences In Oxidative Stress Responses Research Articles

Respiratory responses to hypoxia during rest and exercise in individuals born pre-term: a state-of-the-art review.

The pre-term birth survival rate has increased considerably in recent decades, and research investigating the long-term effects of premature birth is growing. Moreover, altitude sojourns are increasing in popularity and are often accompanied by various levels of physical activity. Individuals born pre-term appear to exhibit altered acute ventilatory responses to hypoxia, potentially predisposing them to high-altitude illness. These impairments are likely due to the use of perinatal hyperoxia stunting the maturation of carotid body chemoreceptors, but may also be attributed to limited lung diffusion capacity and/or gas exchange inefficiency. Aerobic exercise capacity also appears to be reduced in this population. This may relate to the aforementioned respiratory impairments, or could be due to physiological limitations in pulmonary blood flow or at the exercising muscle (e.g. mitochondrial efficiency). However, surprisingly, the debilitative effects of exercise when performed at altitude do not seem to be exacerbated by premature birth. In fact, it is reasonable to speculate that pre-term birth could protect against the consequences of exercise combined with hypoxia. The mechanisms that underlie this assertion might relate to differences in oxidative stress responses or in cardiopulmonary morphology in pre-term individuals, compared to their full-term counterparts. Further research is required to elucidate the independent effects of neonatal treatment, sex differences and chronic lung disease, and to establish causality in some of the proposed mechanisms that could underlie the differences discussed throughout this review. A more in-depth understanding of the acclimatisation responses to chronic altitude exposures would also help to inform appropriate interventions in this clinical population.

Sex differences in early transcriptomic responses to oxidative stress in the copepod Tigriopus californicus

BackgroundPatterns of gene expression can be dramatically different between males and females of the same species, in part due to genes on sex chromosomes. Here we test for sex differences in early transcriptomic response to oxidative stress in a species which lacks heteromorphic sex chromosomes, the copepod Tigriopus californicus.ResultsMale and female individuals were separately exposed to control conditions and pro-oxidant conditions (hydrogen peroxide and paraquat) for periods of 3 hours and 6 hours. Variance partitioning showed the greatest expression variance among individuals, highlighting the important information that can be obscured by the common practice of pooling individuals. Gene expression variance between sexes was greater than that among treatments, showing the profound effect of sex even when males and females share the same genome. Males exhibited a larger response to both pro-oxidants, differentially expressing more than four times as many genes, including up-regulation of more antioxidant genes, heat shock proteins and protease genes. While females differentially expressed fewer genes, the magnitudes of fold change were generally greater, indicating a more targeted response. Although females shared a smaller fraction of differentially expressed genes between stressors and time points, expression patterns of antioxidant and protease genes were more similar between stressors and more GO terms were shared between time points.ConclusionsEarly transcriptomic responses to the pro-oxidants H2O2 and paraquat in copepods revealed substantial variation among individuals and between sexes. The finding of such profound sex differences in oxidative stress response, even in the absence of sex chromosomes, highlights the importance of studying both sexes and the potential for developing sex-specific strategies to promote optimal health and aging in humans.

The Response to Oxidative Stress in Listeria monocytogenes Is Temperature Dependent.

The stress response of 11 strains of Listeria monocytogenes to oxidative stress was studied. The strains included ST1, ST5, ST7, ST6, ST9, ST87, ST199 and ST321 and were isolated from diverse food processing environments (a meat factory, a dairy plant and a seafood company) and sample types (floor, wall, drain, boxes, food products and water machine). Isolates were exposed to two oxidizing agents: 13.8 mM cumene hydroperoxide (CHP) and 100 mM hydrogen peroxide (H2O2) at 10 °C and 37 °C. Temperature affected the oxidative stress response as cells treated at 10 °C survived better than those treated at 37 °C. H2O2 at 37 °C was the condition tested resulting in poorest L. monocytogenes survival. Strains belonging to STs of Lineage I (ST5, ST6, ST87, ST1) were more resistant to oxidative stress than those of Lineage II (ST7, ST9, ST199 and ST321), with the exception of ST7 that showed tolerance to H2O2 at 10 °C. Isolates of each ST5 and ST9 from different food industry origins showed differences in oxidative stress response. The gene expression of two relevant virulence (hly) and stress (clpC) genes was studied in representative isolates in the stressful conditions. hly and clpC were upregulated during oxidative stress at low temperature. Our results indicate that conditions prevalent in food industries may allow L. monocytogenes to develop survival strategies: these include activating molecular mechanisms based on cross protection that can promote virulence, possibly increasing the risk of virulent strains persisting in food processing plants.

Sex differences in oxidative stress responses of tropical topshells (Trochus histrio) to increased temperature and high pCO2

Given scarcity of knowledge on gender ecophysiological responses of tropical marine organisms to global climate change, the major aim of this research was to investigate potential sex differences in oxidative status of topshell Trochus histrio, after a combined exposure to increased temperature and pCO2. Lipid peroxidation, heat-shock response and antioxidant enzymatic activities were evaluated. Lipid peroxidation varied differently between sexes, with males undergoing cellular damage under high pCO2, which was elevated temperature-counteracted. Heat shock response was thermo- and sex-regulated, with males exhibiting significantly higher heat shock proteins production than females. Catalase activity increased with temperature and was exacerbated in combination with hypercapnia, being highest in females, while glutathione S-transferases activity peaked in males. These results clearly support the existence of distinct physiological strategies to cope oxidative stress between sexes, apparently more efficient in females, and also reinforce for the need of encompassing sex as meaningful variable in future biomarker studies.

Salinity-dependent nickel accumulation and oxidative stress responses in the euryhaline killifish (Fundulus heteroclitus).

The mechanisms of nickel (Ni) toxicity in marine fish remain unclear, although evidence from freshwater (FW) fish suggests that Ni can act as a pro-oxidant. This study investigated the oxidative stress effects of Ni on the euryhaline killifish (Fundulus heteroclitus) as a function of salinity. Killifish were exposed to sublethal levels (5, 10, and 20 mg L(-1)) of waterborne Ni for 96 h in FW (0 ppt) and 100 % saltwater (SW) (35 ppt). In general, SW was protective against both Ni accumulation and indicators of oxidative stress [protein carbonyl formation and catalase (CAT) activity]. This effect was most pronounced at the highest Ni exposure level. For example, FW intestine showed increased Ni accumulation relative to SW intestine at 20 mg Ni L(-1), and this was accompanied by significantly greater protein carbonylation and CAT activity in this tissue. There were exceptions, however, in that although liver of FW killifish at the highest exposure concentration showed greater Ni accumulation relative to SW liver, levels of CAT activity were greatly decreased. This may relate to tissue- and salinity-specific differences in oxidative stress responses. The results of the present study suggest (1) that there was Ni-induced oxidative stress in killifish, (2) that the effects of salinity depend on differences in the physiology of the fish in FW versus SW, and (3) that increased levels of cations (sodium, calcium, potassium, and magnesium) and anions (SO4 and Cl) in SW are likely protective against Ni accumulation in tissues exposed to the aquatic environment.

Developmental differences in hyperoxia-induced oxidative stress and cellular responses in the murine lung

Exposure of newborn mice to high inspired oxygen elicits a distinct phenotype of compromised alveolar and vascular development, although lethality during long-term exposure is lower in newborns compared to adults. As the effects of hyperoxia are mediated by excessive reactive oxygen species (ROS) generation, we hypothesized that newborn mice may exhibit enhanced expression of antioxidant defenses or attenuated ROS generation compared with adults. We measured subcellular oxidant responses to acute hyperoxia in lung slices and alveolar epithelial cells at varying time points during postnatal murine lung development. Oxidant stress was assessed using RoGFP, a ratiometric protein thiol redox sensor, targeted to the cytosol or the mitochondrial matrix. In contrast to newborn resistance to oxygen-induced mortality, cells of lung slices from younger mice demonstrated exaggerated mitochondrial matrix oxidant stress compared to adults, whereas oxidant stress responses in the cytosol were absent. Cell death in lung slices from newborn mice exposed to 48h of hyperoxia was also greater than for adults. Consistent with these findings, expression of antioxidant enzymes in newborn lungs was lower than in adults, and induction of antioxidant levels and activity during 24h of in vivo exposure was absent. However, expression of the reactive oxygen species-generating enzyme NADPH oxidase 1 was increased with hyperoxic exposure in the young but not the adult lung. Collectively, these results suggest that the greater lethality in adult animals may be more likely attributed to processes such as inflammation than to differences in antioxidant defenses. Therapies for neonatal and adult oxidative lung injury should therefore consider and address developmental differences in oxidative stress responses.

Transcriptomic comparison of cyanotoxin variants in a human intestinal model revealed major differences in oxidative stress response: Effects of MC-RR and MC-LR on Caco-2 cells

Microcystins (MCs) are cyclic hepatotoxins produced by various species of cyanobacteria. Their structure includes two variable amino acids (AA) giving rise to more than 90 MC variants, however most of the studies to date have focused on the most toxic variant: microcystin LR (MC-LR). Ingestion is the major route of human exposure to MCs and several in vivo studies have demonstrated macroscopic effects on the gastro-intestinal tract. However, little information exists concerning the pathways affected by MC variants on intestinal cells. In the current study, we have investigated the effects of MC-RR and MC-LR on the human intestinal cell line Caco-2 using a non-selective method and compared their response at the pangenomic scale. The cells were incubated for 4h or 24h with a range of non-toxic concentrations of MC-RR or MC-LR. Minimal effects were observed after short term exposures (4h) to either MC variant. In contrast, dose dependent modulations of gene transcription levels were observed with MC-RR and MC-LR after 24h. The transcriptomic profiles induced by MC-RR were quite similar to those induced by MC-LR, suggestive of a largely common mechanism of toxicity. However, changes in total gene expression were more pronounced following exposure to MC-LR compared to MC-RR, as revealed by functional annotation. MC-LR affected two principal pathways, the oxidative stress response and cell cycle regulation, which did not elicit significant alteration following MC-RR exposure. This work is the first comparative description of the effects of MC-LR and MC-RR in a human intestinal cell model at the pangenomic scale. It has allowed us to propose differences in the mechanism of toxicity for MC-RR and MC-LR. These results illustrate that taking into account the toxicity of MC variants remains a key point for risk assessment.

Exposure to waterborne copper reveals differences in oxidative stress response in three freshwater fish species

Among species, various strategies in metal handling can occur. Moreover, the same metal concentration, or even the same metal dose, does not always seem to exert the same effect in different species. Here, we have investigated differences in a copper induced oxidative stress response between rainbow trout ( Oncorhynchus mykiss), common carp ( Cyprinus carpio) and gibel carp ( Carassius auratus gibelio). Fish were exposed to two sub-lethal Cu concentrations, an identical concentration of 50 μg/l for all fish species and an identical toxic dose which was 10% of the concentration lethal to 50% of the fish within 96 h of exposure (LC50 96 h value) for each of the 3 species (20 μg/l for rainbow trout, 65 μg/l for carp and 150 μg/l for gibel carp). Different anti-oxidative enzyme (superoxide dismutase, glutathione reductase and catalase) activities and anti-oxidant (reduced glutathione and reduced ascorbate) concentrations were determined in gill samples collected after 1 h, 12 h, 24 h, 3 days, 1 week and 1 month of Cu exposure. Changes in the measured parameters were present in all 3 species, yet a clear differentiation between fish species could be made before and during the exposure. The ascorbate levels of gibel carp were twice as high as those in common carp or rainbow trout. In contrast, the level of glutathione in rainbow trout was more than twice of that in the two other species. Also, glutathione reductase activity of rainbow trout was higher than in the other species. In rainbow trout a decrease of reduced ascorbate and reduced glutathione was observed in the beginning of the exposure, indicating that ROS scavenging molecules were under pressure. This was followed by an increase in the activity of superoxide dismutase after 3 days of exposure. In contrast, common carp and especially gibel carp enhanced their anti-oxidant enzyme activities as quickly as in the first day of exposure. Furthermore, our research seems to confirm that some fish rely more on glutathione as a first line of defence against metal exposure, while others rely more on metallothionein in combination with anti-oxidant enzymes.

Gender related differences in the oxidative stress response to PCB exposure in an endangered goodeid fish (Girardinichthys viviparus)

Polychlorinated biphenyls (PCBs) are persistent xenobiotics within aquatic environments, which elicit diverse toxic effects such as induction of oxidative stress. Despite numerous earlier studies, no detailed information exists on the toxic response by different sexes in fish. The aim of this study was to determine sex-linked differences in oxidative stress response and antioxidant defenses in Girardinichthys viviparus, an endangered fish endemic to Mexico, when exposed to sub-lethal concentrations of waterborne PCBs. The biological markers evaluated were lipid peroxidation (LPOX), superoxide dismutase (SOD) and catalase (CAT) activity. Adult eight-month-old specimens born in the laboratory were exposed to (1/2) of the LC0 (0.92 mg PCBs/L) in semi-hard synthetic water and sacrificed on days 1, 2, 4, 8 and 16 for biomarker assays. Sex-linked differences were observed in the control fish with respect to all three factors assayed. PCBs elicited significant (p<0.01) time- and sex-dependent LPOX levels which were higher in the case of males. In PCB-treated G. viviparus, SOD activity was depressed in both sexes and appears to return to pre-exposure levels after 16 days in males only. In contrast, CAT was significantly induced (p<0.01) in both sexes. This enzyme may be responsible for balancing oxidative stress and antioxidant defenses under experimental conditions. PCBs at sub-lethal concentrations are hazardous to both sexes of G. viviparus since these compounds are able to induce liver LPOX and changes in the antioxidant defense activities. The relationship between these biomarkers and cytochrome P450 and CYP1A induction is also discussed.

Sex-related responses to oxidative stress in primary cultured hepatocytes of European flounder ( Platichthys flesus L. )

Effects of oxidative stress induced by xenobiotic compounds were studied in primary cultures of isolated hepatocytes of immature European flounder ( Platichthys flesus L.) of both sexes caught in a relatively unpolluted area of the German Bight (North Sea). Cells were exposed to oxidative stressors such as 100 μM hydrogen peroxide (H 2O 2), 100 μM benzo[a]pyrene (B[a]p) and 50 μM nitrofurantoin ( N-(5-nitro-2-furfurylidene)-1-aminohydantoin; NF) for 2 and 24 h. Cell mortality was determined with the use of the fluorescent ethidium homodimer-1 and calcein. Oxidative stress response was assessed by quantitative analysis of (1) intracellular reactive oxygen species (ROS) formation with dihydrorhodamine 123, (2) lipid peroxidation on the basis of concentrations of lipid hydroperoxides and the lipid peroxidation products malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) and (3) cellular total oxidant-scavenging capacity (TOSC) using the TOSC assay ( Winston et al., 1998). An increase in ROS formation was detected as early as 2 h after exposure to H 2O 2, B[a]p and NF. After 24 h, stress responses were lower, except following exposure to NF. The pattern of responses differed with the different oxidative stressors. Lipid peroxidation and the capacity to scavenge ROS were increased significantly in both sexes only after exposure to H 2O 2, whereas B[a]p and NF provoked sex-dependent responses. B[a]p-induced lipid peroxidation and increase in scavenging capacity were observed only in hepatocytes of females, whereas NF initiated these responses only in cells of males. Sex differences in oxidative stress response only after exposure to pro-oxidants that require enzymatic activation infer the importance of biotransformation pathways in stress responses. Because of their sensitivity to oxidative stress, flounder hepatocytes provide a useful model for early risk assessment of xenobiotics.

Interspecies differences in oxidative stress response and radiocesium concentrations in rodents inhabiting areas highly contaminated by the chornobyl nuclear disaster

Indicators of oxidative stress response were compared to radionuclide concentrations in rodents from highly contaminated sites around the Chornobyl Nuclear Power Plant, Ukraine, and uncontaminated reference areas. Three rodent species-Apodemus agrarius, Apodemus sylvaticus, and Clethrionomys glareolus (n = 121)-were collected from contaminated sites within the 10-km exclusion zone surrounding the Chornobyl Nuclear Power Plant and from uncontaminated reference areas in northern Ukraine. Liver samples were analyzed for superoxide dismutase (SOD) and catalase (CAT) activities, and muscle samples were analyzed for radiocesium activity. Superoxide dismutase and catalase activities differed significantly between reference and contaminated groups only for A. agrarius, and activities were lower in contaminated animals relative to those from reference sites. The SOD activity did not differ among species collected in reference areas. Among contaminated groups, A. agrarius had a significantly lower SOD activity than the other two species. Among reference groups, CAT activity for C. glareolus was significantly lower than for the other two species. Very high muscle radiocesium activities (up to 60,000 Bq/g) were found in rodents from contaminated areas, while the references for each species were at or below background. Clethrionomys glareolus had significantly higher muscle radiocesium concentrations than the other species collected at contaminated sites. There were no significant correlations between either SOD or CAT activities and muscle radiocesium concentrations for contaminated or reference animals in any species. There are significant interspecies differences in oxidative enzyme activities in rodents with lifetime exposure at highly radioactive contaminated sites. However, internal radiocesium concentration is not a sensitive predictor of these oxidative stress responses in individuals.