523. PLACENTAL ANTIOXIDANT ENZYMES IN RAT PREGNANCY SHOW ZONE- AND STAGE-DEPENDENT VARIATION

Placental oxidative stress plays a key role in the pathophysiology of placenta-related disorders including preeclampsia. Protection from oxidative stress is provided by antioxidant enzymes which inactivate reactive oxygen species (ROS). The rat placenta consists of two major zones, the junctional (JZ) and labyrinth (LZ), and because only the LZ grows in late gestation we hypothesized it generates more ROS and thus requires greater antioxidant protection. Our previous studies on expression of the antioxidants superoxide dismutase (SOD)-1, SOD-2 and catalase support this hypothesis. Here, we extend these observations to include mRNA expression of SOD-3 and thioredoxin reductases (Txnrd-1, -2, -3) and activities of SOD, hydrogen peroxide (H2O2) scavenging and xanthine oxidase (XO). Placental oxidative damage was assessed by measurement of F2-isoprostanes and TBARS concentrations. We also measured the effects of maternal dexamethasone treatment, since glucocorticoid excess is known to induce oxidative damage in other tissues. Placentas were collected from untreated mothers on days 16 and 22 (term=day 23) and on day 22 after dexamethasone treatment from day 13 (1 μg/ml drinking water). SOD-3, Txnrd-1, -2, and -3 mRNAs were measured in JZ and LZ by qRT-PCR. F2-isoprostanes were measured by GC-MS and kit assays were used to measure TBARS and the activities of SOD, H2O2 scavenging and XO. In both placental zones, expression of SOD-3 and Txnrd-1 mRNAs and H2O2 scavenging activity decreased from day 16 to 22, whereas XO activity increased. Dexamethasone treatment increased H2O2 scavenging in both zones, but had no effect on SOD or XO activities or antioxidant mRNA expression. Despite predicted increases in placental ROS generation in late pregnancy and after dexamethasone, neither F2-isoprostanes nor TBARS were increased. These and our previous data suggest that endogenous protection against oxidative stress is abundant in the rat placenta and provides protection against potential oxidative insults including glucocorticoid excess.

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215. Placental expression of uncoupling protein-2 is reduced by glucocorticoid treatment in late pregnancy: implications for placental oxidative stress

Reproduction Fertility and Development ◽

10.1071/srb08abs215 ◽

2008 ◽

Vol 20 (9) ◽

pp. 15

Author(s):

M. L. Jones ◽

P. J. Mark ◽

B. J. Waddell

Keyword(s):

Oxidative Stress ◽

Gestational Age ◽

Uncoupling Protein ◽

Late Pregnancy ◽

Uncoupling Protein 2 ◽

Dexamethasone Treatment ◽

Glucocorticoid Treatment ◽

Ucp2 Expression ◽

Endogenous Protection ◽

Placental Oxidative Stress

Placental oxidative stress plays a key role in the pathophysiology of placenta-related disorders in humans, most notably in preeclampsia (PE) and intrauterine growth restriction (IUGR). Protection from oxidative stress is provided by antioxidant enzymes including superoxide dismutase-1 and 2 (SOD-1 and –2) and catalase (CAT), which convert reactive oxygen species (ROS) to inert products. It has also been proposed that uncoupling protein-2 (UCP2) may limit oxidative stress by reducing ROS production, but little is known of UCP2 expression in placenta. Here we measured placental UCP2, SOD-1, SOD-2 and CAT mRNA expression (by qRT–PCR) in normal gestation and after glucocorticoid-induced IUGR. The latter was included because glucocorticoids can increase oxidative stress in other tissues, and placental glucocorticoid exposure is elevated in both PE and IUGR. Placentas were collected on days 16 and 22 of normal pregnancy (term = day 23) and on day 22 after dexamethasone treatment (0.75 mg/mL in drinking water from day 13). The two morphologically-distinct regions of the placenta, the junctional (JZ) and labyrinth (LZ) zones, were analysed separately because effectively all growth occurs in the LZ over this period. Expression of UCP2 in LZ exceeded that in JZ (P < 0.001) and increased in both zones between days 16 and 22 (LZ: 2.0-fold; JZ: 3.2-fold). Dexamethasone treatment reduced UCP2 in LZ (44%; P < 0.05) but not in JZ. SOD1 and SOD2 increased with gestational age in LZ (P < 0.01) and JZ (P < 0.05), but neither were affected by dexamethasone. CAT expression was higher (2.4-fold, P < 0.001) in LZ compared with JZ but did not change with gestational age or dexamethasone. In summary, these data suggest that endogenous protection against oxidative stress increases in the rat placenta during late pregnancy. Moreover, this protection may be compromised by reduced placental UCP2 expression in a model of glucocorticoid-induced IUGR.

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Abstract 067: Downregulation Of Vascular Factor-erythroid 2-related Factor-2 And Associated Antioxidant Enzymes In Hypertension

Hypertension ◽

10.1161/hyp.64.suppl_1.067 ◽

2014 ◽

Vol 64 (suppl_1) ◽

Author(s):

Rheure A Lopes ◽

Karla B Neves ◽

Augusto Montezano ◽

Rita Tostes ◽

Rhian Touyz

Keyword(s):

Oxidative Stress ◽

Antioxidant Enzymes ◽

Mrna Expression ◽

Vascular Dysfunction ◽

Ros Generation ◽

Related Factor ◽

Mrna Levels ◽

Ang Ii ◽

Peroxiredoxin 1 ◽

Anti Oxidant

Oxidative stress plays an important role in vascular dysfunction in hypertension. While mechanisms regulating vascular pro-oxidants are emerging, there is a paucity of information on anti-oxidant systems. Factor-erythroid 2-related factor-2 (Nrf2) is a master regulator of antioxidants and its role in hypertension remains elusive. We assessed vascular Nrf2 in hypertension by studying mesenteric vessels and VSMCs from WKY and SHRSP rats. Cells were stimulated with Ang II (10-7M) in the absence/presence of Nrf2 activators (bardoxolone or L-sulforaphane). ROS generation was assessed by chemiluminescence and amplex red. mRNA expression of anti-oxidant enzymes was assessed by qPCR. Nrf2 activity was analyzed by ELISA. Nrf2 activity was decreased in arteries (18%) and VSMCs (48%) in SHRSP (p<0.05 vs WKY). mRNA levels of antioxidant enzymes were reduced in SHRSP (SOD 1 (64%), catalase (60%), peroxiredoxin 1 (75%) and glutathione peroxidase (54%) Ang II increased Nrf2 activity in VSMCs from WKY (197%, 4h) and SHRSP (44%, 4h) (p<0.05, vs. vehicle). This was associated with increased antioxidant mRNA expression in WKY rats (SOD1-32%, catalase-42%, thioredoxin-71%, peroxiredoxin 1-90%, quinone oxidoreductase-84%; p<0.05 vs. vehicle) but not in SHRSP. ROS production and glucose-6-phosphate dehydrogenase (source of NADPH) mRNA levels were increased in SHRSP. Ang II-induced ROS generation in VSMCs from WKY and SHRSP was blocked by Nrf2 activators. Vascular function assessment, by wire myography, demonstrated that increased contractility (Emax Phe: WKY 113.4±5,67 vs. SHRSP 159.0±8.29) and decreased endothelial-dependent relaxation (Emax ACh: WKY 88.7±3.13 vs. SHRSP 74.7±3.25, p<0.05) in SHRSP were corrected by bardoxolone and L-sulforaphane. In conclusion, vascular dysfunction in SHRSP is associated with oxidative stress, decreased Nrf2 activity and reduced Nrf2-regulated antioxidant enzymes. A similar molecular phenotype was observed in Ang II-stimulated VSMCs. Nrf-2 agonists ameliorated vascular dysfunction in SHRSP. Our findings suggest that Nrf-2 downregulation may contribute to redox-sensitive vascular dysfunction and could be a therapeutic target in hypertension. Financial Support: ScWB.

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Exercise protects against doxorubicin-induced oxidative stress and proteolysis in skeletal muscle

Journal of Applied Physiology ◽

10.1152/japplphysiol.00677.2010 ◽

2011 ◽

Vol 110 (4) ◽

pp. 935-942 ◽

Cited By ~ 69

Author(s):

Ashley J. Smuder ◽

Andreas N. Kavazis ◽

Kisuk Min ◽

Scott K. Powers

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Antioxidant Enzymes ◽

Heat Shock ◽

Heat Shock Protein ◽

Oxidative Damage ◽

Muscle Fibers ◽

Muscular Exercise ◽

Protease Activation ◽

Exercise Induced

Doxorubicin (Dox) is a potent antitumor agent used in cancer treatment. Unfortunately, Dox is myotoxic and results in significant reductions in skeletal muscle mass and function. Complete knowledge of the mechanism(s) by which Dox induces toxicity in skeletal muscle is incomplete, but it is established that Dox-induced toxicity is associated with increased generation of reactive oxygen species and oxidative damage within muscle fibers. Since muscular exercise promotes the expression of numerous cytoprotective proteins (e.g., antioxidant enzymes, heat shock protein 72), we hypothesized that muscular exercise will attenuate Dox-induced damage in exercise-trained muscle fibers. To test this postulate, Sprague-Dawley rats were randomly assigned to the following groups: sedentary, exercise, sedentary with Dox, or exercise with Dox. Our results show increased oxidative stress and activation of cellular proteases (calpain and caspase-3) in skeletal muscle of animals treated with Dox. Importantly, our findings reveal that exercise can prevent the Dox-induced oxidative damage and protease activation in the trained muscle. This exercise-induced protection against Dox-induced toxicity may be due, at least in part, to an exercise-induced increase in muscle levels of antioxidant enzymes and heat shock protein 72. Together, these novel results demonstrate that muscular exercise is a useful countermeasure that can protect skeletal muscle against Dox treatment-induced oxidative stress and protease activation in skeletal muscles.

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Oxidative Stress, Mitochondrial DNA Mutation, and Impairment of Antioxidant Enzymes in Aging

Experimental Biology and Medicine ◽

10.1177/153537020222700901 ◽

2002 ◽

Vol 227 (9) ◽

pp. 671-682 ◽

Cited By ~ 377

Author(s):

Yau-Huei Wei ◽

Hsin-Chen Lee

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dna ◽

Antioxidant Enzymes ◽

Oxidative Damage ◽

Large Scale ◽

Wide Spectrum ◽

Radical Scavenging ◽

Mtdna Mutations ◽

Enhanced Production ◽

Age Related

Mitochondria do not only produce less ATP, but they also increase the production of reactive oxygen species (ROS) as byproducts of aerobic metabolism in the aging tissues of the human and animals. It is now generally accepted that aging-associated respiratory function decline can result in enhanced production of ROS in mitochondria. Moreover, the activities of free radical-scavenging enzymes are altered in the aging process. The concurrent age-related changes of these two systems result in the elevation of oxidative stress in aging tissues. Within a certain concentration range, ROS may induce stress response of the cells by altering expression of respiratory genes to uphold the energy metabolism to rescue the cell. However, beyond the threshold, ROS may cause a wide spectrum of oxidative damage to various cellular components to result in cell death or elicit apoptosis by induction of mitochondrial membrane permeability transition and release of apoptogenic factors such as cytochrome c. Moreover, oxidative damage and large-scale deletion and duplication of mitochondrial DNA (mtDNA) have been found to increase with age in various tissues of the human. Mitochondria act like a biosensor of oxidative stress and they enable cell to undergo changes in aging and age-related diseases. On the other hand, it has recently been demonstrated that impairment in mitochondrial respiration and oxidative phosphorylation elicits an increase in oxidative stress and causes a host of mtDNA rearrangements and deletions. Here, we review work done in the past few years to support our view that oxidative stress and oxidative damage are a result of concurrent accumulation of mtDNA mutations and defective antioxidant enzymes in human aging.

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ANTIOXIDATIVE DEFENSE RESPONSE TO APHID-INDUCED OXIDATIVE STRESS IN Glycine max (L.) Merr. cv. “Nam Dan”

Vietnam Journal of Science and Technology ◽

10.15625/0866-708x/54/6/7952 ◽

2016 ◽

Vol 54 (6) ◽

pp. 719 ◽

Cited By ~ 1

Author(s):

Tran Ngoc Toan ◽

Tran Thi Van Thanh Huyen ◽

Mai Van Chung

Keyword(s):

Oxidative Stress ◽

Glycine Max ◽

Oxidative Damage ◽

Thiobarbituric Acid ◽

Ros Generation ◽

Oxygen Species ◽

Thiobarbituric Acid Reactive Substances ◽

Aphis Craccivora Koch ◽

Glycine Max L ◽

Aphid Feeding

Infestation of cowpea aphid (Aphis craccivora Koch) induced oxidative stress in leaves of soybean (Glycine max (L.) Merr. cv. “Nam Dan”) with a burst in generation of reactive oxygen species (ROS) products such as superoxide anion radical (O2.-) and hydrogen peroxide (H2O2) recorded around 24 hours after aphid feeding. An increase in content of thiobarbituric acid reactive substances (TBARS) in lipid peroxidation and a defined percentage of injury in aphid-infested leaves were resulted from the cellular oxidative damage. The enhanced activity of the antioxidant enzymes such as superoxide dismutase (SOD, EC 1.15.1.1) and catalase (CAT, EC 1.11.1.6) in leaves of soybean “Nam Dan” functions as the antioxidative response that controlled both ROS-generation to be enough levels to play as defensive element and ROS-detoxifying to reduce aphid-induced oxidative damage. The enhancement of SOD and CAT also can improve the tolerance of soybean “Nam Dan” to impact from A. craccivora.

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Pechiche (Vitex cymosa Berteo ex Speng), a Nontraditional Fruit from Ecuador, is a Dietary Source of Phenolic Acids and Nutrient Minerals, in Addition to Efficiently Counteracting the Oxidative-Induced Damage in Human Dermal Fibroblasts

Antioxidants ◽

10.3390/antiox9020109 ◽

2020 ◽

Vol 9 (2) ◽

pp. 109

Author(s):

Mabel Guevara ◽

Luis A. Valdés-Silverio ◽

María G. Granda-Albuja ◽

Gabriel Iturralde ◽

Tatiana Jaramillo-Vivanco ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Enzymes ◽

Oxidative Damage ◽

Phenolic Acids ◽

Glutathione Transferase ◽

Dermal Fibroblasts ◽

Human Dermal Fibroblasts ◽

Atp Levels ◽

Intracellular Ros ◽

Phosphorus And Potassium

Pechiche fruits (Vitex cymosa Berteo ex Speng) from Ecuador were studied to determine their phenolic acid profile, nutrient minerals and capacity to protect primary human dermal fibroblasts (HDFa) against oxidative-induced damage. Up to five phenolic acids were identified, with homovanillic acid as the main one. Vitamin C, β-carotene and lutein were also determined. Phosphorus and potassium were the main macrominerals, while iron was the principal micromineral. HDFa were preincubated with a crude pechiche extract (PCext) and then subjected to oxidative stress. The activity of five antioxidant enzymes, intracellular reactive oxygen species (ROS) and ATP levels and lipid peroxidation and protein oxidation were used as markers of oxidative damage. Preincubation with PCext for 24 h allowed for the significant reduction of intracellular ROS levels, improved the intracellular ATP levels and protected lipids and proteins against oxidative damage (p < 0.05). Additionally, preincubation with PCext was also able to significantly (p < 0.05) improve the activity of the antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and glutathione transferase, compared to the stressed group without pretreatment. The results obtained in this study suggest the potential of pechiche as a source of bioactive compounds, as well as its beneficial effect against oxidative stress.

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Effect of Dietary Hemp Seed on Oxidative Status in Sows during Late Gestation and Lactation and Their Offspring

Animals ◽

10.3390/ani9040194 ◽

2019 ◽

Vol 9 (4) ◽

pp. 194 ◽

Cited By ~ 5

Author(s):

Laurentiu Mihai Palade ◽

Mihaela Habeanu ◽

Daniela Eliza Marin ◽

Veronica Sanda Chedea ◽

Gina Cecilia Pistol ◽

...

Keyword(s):

Lipid Peroxidation ◽

Antioxidant Enzymes ◽

Control Diet ◽

Thiobarbituric Acid ◽

Oxidative Status ◽

Late Gestation ◽

Control Group ◽

Ros Generation ◽

Lactation Period ◽

Hemp Seed

This study shows the antioxidant effect of a dietary hemp seed diet rich in ω-6 polyunsaturated fatty acid (PUFA) on oxidative status in sows during late gestation and lactation and their offspring. Ten pregnant sows were divided into two groups and fed either a control diet (CD) or a hemp diet (HD) containing 2% hemp seed meal for a period of 10 days before farrowing and 5% throughout the lactation period (21 d). After farrowing, 16 of their resulting piglets were divided into two groups: control group CD (eight piglets derived from control sows) and HD group (eight piglets derived from HD sows), respectively. Blood collected from sows and piglets at day 1, 7 and 21 was used for the measurement of antioxidant enzymes (catalase (CAT), superoxide dismutase (SOD), glutathione (GPx)), nitric oxide production (NO), lipid peroxidation (thiobarbituric acid reactive substances—TBARS), reactive oxygen species (ROS) generation and total antioxidant capacity (TAC) in plasma. The results showed a significant improvement in the oxidative status of sows fed HD throughout lactation compared with CD. Similarly, in piglets, HD positively influenced the activities of antioxidant enzymes, TAC and NO levels and significantly decreased lipid peroxidation in plasma until weaning, in comparison with the CD group. This study suggests the potential of hemp seed diet to improve the overall antioxidant status of the lactating sows and their progeny.

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Reduced mitochondrial ROS, enhanced antioxidant defense, and distinct age-related changes in oxidative damage in muscles of long-lived Peromyscus leucopus

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00139.2012 ◽

2013 ◽

Vol 304 (5) ◽

pp. R343-R355 ◽

Cited By ~ 25

Author(s):

Yun Shi ◽

Daniel A. Pulliam ◽

Yuhong Liu ◽

Ryan T. Hamilton ◽

Amanda L. Jernigan ◽

...

Keyword(s):

Oxidative Stress ◽

Oxidative Damage ◽

Peromyscus Leucopus ◽

Laboratory Mouse ◽

Linear Increase ◽

Young Age ◽

Protein Carbonyls ◽

Ros Generation ◽

Glutathione Peroxidase 1 ◽

Age Related

Comparing biological processes in closely related species with divergent life spans is a powerful approach to study mechanisms of aging. The oxidative stress hypothesis of aging predicts that longer-lived species would have lower reactive oxygen species (ROS) generation and/or an increased antioxidant capacity, resulting in reduced oxidative damage with age than in shorter-lived species. In this study, we measured ROS generation in the young adult animals of the long-lived white-footed mouse, Peromyscus leucopus (maximal life span potential, MLSP = 8 yr) and the common laboratory mouse, Mus musculus (C57BL/6J strain; MLSP = 3.5 yr). Consistent with the hypothesis, our results show that skeletal muscle mitochondria from adult P. leucopus produce less ROS (superoxide and hydrogen peroxide) compared with M. musculus. Additionally, P. leucopus has an increase in the activity of antioxidant enzymes superoxide dismutase 1, catalase, and glutathione peroxidase 1 at young age. P. leucopus compared with M. musculus display low levels of lipid peroxidation (isoprostanes) throughout life; however, P. leucopus although having elevated protein carbonyls at a young age, the accrual of protein oxidation with age is minimal in contrast to the linear increase in M. musculus. Altogether, the results from young animals are in agreement with the predictions of the oxidative stress hypothesis of aging with the exception of protein carbonyls. Nonetheless, the age-dependent increase in protein carbonyls is more pronounced in short-lived M. musculus, which supports enhanced protein homeostasis in long-lived P. leucopus.

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The Effects of Moderate, Strenuous, and Overtraining on Oxidative Stress Markers and DNA Repair in Rat Liver

Canadian Journal of Applied Physiology ◽

10.1139/h05-114 ◽

2005 ◽

Vol 30 (2) ◽

pp. 186-195 ◽

Cited By ~ 53

Author(s):

Helga Ogonovszky ◽

Maria Sasvári ◽

Agoston Dosek ◽

István Berkes ◽

Takao Kaneko ◽

...

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Antioxidant Enzymes ◽

Oxidative Damage ◽

Rat Liver ◽

Nuclear Dna ◽

Activity Levels ◽

Carbonyl Derivative ◽

Stress Markers ◽

Cell Extracts

Physical exercise above a certain load has been suggested as being a cause of oxidative stress. We have tested whether training with moderate (MT), strenuous (ST), or over (OT) load can cause alterations in the activities of antioxidant enzymes, lipid peroxidation, protein oxidation, DNA damage, or activity of 8-oxoG-DNA glycosylase (OGG1) in rat liver. The levels of corticosterone decreased in all exercising groups but the differences were not significant. Adrenocorticotrophin hormone (ACTH) levels decreased, not significantly, in MT and OT compared to C. Activity levels of antioxidant enzymes did not change significantly in the liver. The levels of reactive carbonyl derivative (RCD) content decreased in the liver of exercising animals, and the differences reached significance between control and moderately trained groups. The changes in the levels of lipid peroxidation (LIPOX) were not significant, but were lower in the exercised groups. The 8-hydroxydeoxyguanosine (8-OHdG) levels increased in the OT group, and the activity of OGG1 measured from crude cell extracts tended to increase in MT and ST. The findings of this study imply that overtraining induces oxidative damage to nuclear DNA, but not to liver lipids and proteins. Key words: exercise, oxidative damage, adaptation, OGG1

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Regulation of Reactive Oxygen Species and Antioxidant Defense in Plants under Salinity

International Journal of Molecular Sciences ◽

10.3390/ijms22179326 ◽

2021 ◽

Vol 22 (17) ◽

pp. 9326

Author(s):

Mirza Hasanuzzaman ◽

Md. Rakib Hossain Raihan ◽

Abdul Awal Chowdhury Masud ◽

Khussboo Rahman ◽

Farzana Nowroz ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Salt Stress ◽

Oxidative Damage ◽

Antioxidant Defense ◽

Reactive Oxygen ◽

Antioxidant Defense System ◽

Ros Generation ◽

Oxygen Species ◽

Defense System

The generation of oxygen radicals and their derivatives, known as reactive oxygen species, (ROS) is a part of the signaling process in higher plants at lower concentrations, but at higher concentrations, those ROS cause oxidative stress. Salinity-induced osmotic stress and ionic stress trigger the overproduction of ROS and, ultimately, result in oxidative damage to cell organelles and membrane components, and at severe levels, they cause cell and plant death. The antioxidant defense system protects the plant from salt-induced oxidative damage by detoxifying the ROS and also by maintaining the balance of ROS generation under salt stress. Different plant hormones and genes are also associated with the signaling and antioxidant defense system to protect plants when they are exposed to salt stress. Salt-induced ROS overgeneration is one of the major reasons for hampering the morpho-physiological and biochemical activities of plants which can be largely restored through enhancing the antioxidant defense system that detoxifies ROS. In this review, we discuss the salt-induced generation of ROS, oxidative stress and antioxidant defense of plants under salinity.

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