Serum superoxide dismutase 3 (extracellular superoxide dismutase) activity is a sensitive indicator of Cu status in rats

Johnson, W. Thomas; Johnson, Lu Ann K.; Lukaski, Henry C.

doi:10.1016/j.jnutbio.2005.03.009

Cited by 40 publications

(18 citation statements)

References 35 publications

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“…It is mainly produced by vascular smooth muscle cells and retained in the vascular wall, and therefore mainly absent in erythrocytes and other blood cells (Nozik-Grayck et al, 2005). Superoxide dismutase 3 is mainly responsible for the SOD activity found in plasma and serum (Nozik-Grayck et al, 2005;Tasaki et al, 2006), and decreased copper levels inhibit its activity in rats (Johnson et al, 2005). Superoxide dismutase 3 activity in human plasma is low, but increases upon treatment with heparin (Tasaki et al, 2006).…”

Section: Resultsmentioning

confidence: 99%

Identification of biomarkers for the antiangiogenic and antitumour activity of the superoxide dismutase 1 (SOD1) inhibitor tetrathiomolybdate (ATN-224)

Doñate¹,

Juarez²,

Burnett³

et al. 2008

Br J Cancer

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Tetrathiomolybdate (choline salt; ATN-224), a specific, high-affinity copper binder, is currently being evaluated in several phase II cancer trials. ATN-224 inhibits CuZn superoxide dismutase 1 (SOD1) leading to antiangiogenic and antitumour effects. The pharmacodynamics of tetrathiomolybdate has been followed by tracking ceruloplasmin (Cp), a biomarker for systemic copper. However, at least in mice, the inhibition of angiogenesis occurs before a measurable decrease in systemic copper is observed. Thus, the identification and characterisation of other biomarkers to follow the activity of ATN-224 in the clinic is of great interest. Here, we present the preclinical evaluation of two potential biomarkers for the activity of ATN-224: (i) SOD activity measurements in blood cells in mice and (ii) levels of endothelial progenitor cells (EPCs) in bonnet macaques treated with ATN-224. The superoxide dismutase activity in blood cells in mice is rapidly inhibited by ATN-224 treatment at doses at which angiogenesis is maximally inhibited. Furthermore, ATN-224 dosing in bonnet macaques causes a profound and reversible decrease in EPCs without significant toxicity. Thus, both SOD activity measurements and levels of EPCs may be useful biomarkers of the antiangiogenic activity of ATN-224 to be used in its clinical development.

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Section: Resultsmentioning

confidence: 99%

Identification of biomarkers for the antiangiogenic and antitumour activity of the superoxide dismutase 1 (SOD1) inhibitor tetrathiomolybdate (ATN-224)

Doñate¹,

Juarez²,

Burnett³

et al. 2008

Br J Cancer

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“…Unlike the human EC-SOD, rat SOD exists as a dimer and has a poor affinity for heparin, which may explain the higher concentration found in rat plasma compared with human plasma. 119 EC-SOD has also been implicated in the antioxidant defense of hamsters after arousal from hibernation, during which reperfusion accompanying the increase in cardiac output leads to a state of transient oxidant stress. 120 The different affinities of EC-SOD may regulate its cellular distribution and its function.…”

Section: Extracellular Antioxidant Enzymes Extracellular Superoxide Dmentioning

confidence: 99%

Redox Regulation in the Extracellular Environment

Ottaviano

Handy

Loscalzo

2008

Circ J

128

100

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Molecular oxygen is involved in the oxidation of substrates used to produce energy; however, normal metabolism can also generate harmful (bio)chemical byproducts. These deleterious products are partially reduced forms of oxygen, and include free radicals such as superoxide anion radical, hydroxyl radical, or highly oxidizing non-radical species such as hydrogen peroxide (H2O2) and lipid peroxides, which are collectively known as ROS. 1 ROS typically derive from normal metabolism, activated leukocytes, and ambient oxygen in the environment. The production and accumulation of ROS and their downstream effects can be controlled or attenuated by antioxidants. When the ability of antioxidants to eliminate harmful cellular and extracellular ROS is compromised, the balance between ROS generation and antioxidant function to eliminate ROS is shifted in favor of an accumulation of oxidants, which defines the state of oxidative stress in a cell or organism. Oxidative damage can affect DNA, lipids, and proteins, and eventually compromise cell integrity. Many studies have implicated ROS in the pathological processes leading to heart disease, cancer, aging, AIDS, and inflammatory and autoimmune diseases.Oxidants, especially free radicals, are highly reactive. Superoxide can react within milliseconds with nitric oxide (NO) to produce peroxynitrite (ONOO -), a reactive nitrogen species (RNS). The nitrosium cation and nitroxyl anion are other RNS derived from NO. 2 Peroxynitrite is a strong oxidant involved in the nitrosative modification of proteins and lipids. Owing to its rapid reaction with NO, superoxide may modulate NO bioavailability and, subsequently, regulate vascular function. 3 Circulation Journal Vol.72, January 2008The cytosol, mitochondria, peroxisomes, and plasma are all potential sites of ROS formation. 4 The major sources of ROS are enzymatic via nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox), xanthine oxidase, myeloperoxidase, endothelial NO synthase (eNOS), or as a consequence of normal mitochondrial respiration. In vascular cells, other enzymatic sources of ROS include cytochrome P450 isoenzymes, lipoxygenase, cyclooxygenase, heme oxygenase, and glucose oxidase. 1,3,[5][6][7] Most reviews to date have focused on the role of intracellular antioxidants that eliminate ROS from the intracellular environment. There are, however, several extracellular antioxidants that also play an equally important role in limiting ROS accumulation in the extracellular environment. Along with limiting ROS accumulation, extracellular redox status is essential for maintaining protein stability and function.The major enzymes important for the elimination of extracellular H2O2 are glutathione peroxidase-3 (GPx-3) and peroxiredoxin IV (Prx IV). Other extracellular antioxidants involved in ROS elimination include paraoxonase (PON), thioredoxin (Trx), Trx reductase (TrxR), glutaredoxin (Grx), extracellular superoxide dismutase (EC-SOD), and extracellular glutathione (GSH).Some of these antioxidants, notably glutathione...

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“…Superoxide dismutase (SODs) belong to a group of antioxidant enzymes that catalyse the dismutation of superoxide to produce hydrogen peroxide and oxygen [47]. SOD is essentially a protective enzyme which scavenges the superoxide ions produced as cellular by-products during oxidative stress [48].…”

Section: Results:-mentioning

confidence: 99%

The Therapeutic Role of Vitamin E or Zinc and Their Mixture Supplementation on Some Heavy Metals-Induced Testicular Functions Injuries in Male Rats.

Ibrahim.¹

2017

IJAR

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Background: Toxic heavy metals in water, air and soil are global problems that are a growing threat to humanity. Heavy metals are widely distributed in the environment and some of them occur in food, water, air and tissues even in the absence of occupational exposure. Aim: To investigate the antioxidant and protective influences of vitamin E and/or zinc on some heavy metals (lead, cadmium and mercury) induced oxidative stress and testicular injuries in male rats. Results: Results showed that exposure to lead, cadmium or/and mercury causes damage or alterations in the testicular functions in male albino rats. On the other hand, vitamin E or/and zinc administration lessened or cured these damages and repaired the destruction which occurred because of exposure to these toxic substances. Conclusion: heavy metals stimulated different hazardous effects leading to testicular dysfunction in male rats, and the supplementation of vitamin E or/and zinc play(s) an important role to minimize and reduce the harmful effects of heavy metal exposure. These improvements are attributed to the antioxidant functions of vitamin E and zinc. In addition, suggestions for further studies were recommended.

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Serum superoxide dismutase 3 (extracellular superoxide dismutase) activity is a sensitive indicator of Cu status in rats

Cited by 40 publications

References 35 publications

Identification of biomarkers for the antiangiogenic and antitumour activity of the superoxide dismutase 1 (SOD1) inhibitor tetrathiomolybdate (ATN-224)

Identification of biomarkers for the antiangiogenic and antitumour activity of the superoxide dismutase 1 (SOD1) inhibitor tetrathiomolybdate (ATN-224)

Redox Regulation in the Extracellular Environment

The Therapeutic Role of Vitamin E or Zinc and Their Mixture Supplementation on Some Heavy Metals-Induced Testicular Functions Injuries in Male Rats.

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