Extracellular-Superoxide Dismutase Type C (EC-SOD C) Reduces Myocardial Damage in Rats Subjected to Coronary Occlusion and 24 Hours of Reperfusion

Wahlund, Göran; Marklund, Stefan L.; Sjöquist, Per-Ove

doi:10.3109/10715769209061087

Cited by 14 publications

(8 citation statements)

References 35 publications

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“…Lipid peroxidation levels in liver and serum were measured using an assay for thiobarbituric acid reactive substances (TBARS) [ 16 ]. SOD activity was assayed in the serum and liver using a technique that involves inhibition of pyrogallol auto oxidation at pH 8.0 [ 17 ].…”

Section: Methodsmentioning

confidence: 99%

Alcohol-induced Hyperlipidemia Is Ameliorated by Orally Administered DWP208, a Sodium Succinate Form of ZYM201

Cho

Choi

Park

et al. 2014

Korean J Physiol Pharmacol

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DWP208 is a sodium succinate form of ZYM-201 which is a triterpenoid glycoside isolated from Sanguisorba officinalis, a medicinal plant prescribed for various diseases, such as duodenal ulcers and bleeding in East Asian counties. We demonstrated that this compound is able to normalize the altered lipid metabolism induced by hyperglycemia and a high fat diet. In this study, we determined whether hyperlipidemic conditions induced with chronically treated alcohol can also be restored by DWP208. Similar to our previous results, orally administered DWP208 (1 to 10 mg/kg) also ameliorated the hyperlipidemia that was induced by alcohol. This compound reversed the alcohol-induced hyperlipidemia including (i) up-regulated hyperlipidemic parameters such as low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), atherosclerotic index (AI), triglyceride, and total cholesterol, and (ii) down-regulated hyperlipidemic parameters such as absolute body weight, superoxide dismutase (SOD) activity, and high-density lipoprotein (HDL) in serum and liver. According to our data, the ameliorative activity of DWP208 is due to its indirect anti-oxidative activity as a result of which lipid peroxide and hydroxyl radical levels were reduced and the activity of SOD was enhanced. Therefore, our data strongly suggest that DWP208 can be used as a remedy against alcohol-induced hyperlipidemia.

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Section: Methodsmentioning

confidence: 99%

Alcohol-induced Hyperlipidemia Is Ameliorated by Orally Administered DWP208, a Sodium Succinate Form of ZYM201

Cho

Choi

Park

et al. 2014

Korean J Physiol Pharmacol

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“…The artificial ECSOD so produced exerted a strong antiinflammatory effect. ECSOD also protects against reperfusion injury (155)(156)(157)(158), enhances arterial relaxation (159), and thereby diminishes hyper tension (160). ECSOD may prove to be a useful pharmaceutical, and the production of transgenic mice that secrete the human ECSOD in milk has clearly brought us closer to realizing a convenient source (161).…”

Section: Extracellular Sods (Ecsods)mentioning

confidence: 99%

Superoxide Radical and Superoxide Dismutases

Fridovich

1995

Annu. Rev. Biochem.

3,002

1,499

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O2- oxidizes the [4Fe-4S] clusters of dehydratases, such as aconitase, causing-inactivation and release of Fe(II), which may then reduce H2O2 to OH- +OH.. SODs inhibit such HO. production by scavengingO2-, but Cu, ZnSODs, by virtue of a nonspecific peroxidase activity, may peroxidize spin trapping agents and thus give the appearance of catalyzing OH. production from H2O2. There is a glycosylated, tetrameric Cu, ZnSOD in the extracellular space that binds to acidic glycosamino-glycans. It minimizes the reaction of O2- with NO. E. coli, and other gram negative microorganisms, contain a periplasmic Cu, ZnSOD that may serve to protect against extracellular O2-. Mn(III) complexes of multidentate macrocyclic nitrogenous ligands catalyze the dismutation of O2- and are being explored as potential pharmaceutical agents. SOD-null mutants have been prepared to reveal the biological effects of O2-. SodA, sodB E. coli exhibit dioxygen-dependent auxotrophies and enhanced mutagenesis, reflecting O2(-)-sensitive biosynthetic pathways and DNA damage. Yeast, lacking either Cu, ZnSOD or MnSOD, are oxygen intolerant, and the double mutant was hypermutable and defective in sporulation and exhibited requirements for methionine and lysine. A Cu, ZnSOD-null Drosophila exhibited a shortened lifespan.

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“…Of the three SOD isoforms, ecSOD expression levels are lowest in the heart based on expression levels and relative SOD activity. However, overexpression of ecSOD or treatment with SOD mimetics [31, 32, 60] has been shown to attenuate oxidative stress and to mitigate tissue dysfunction in cardiovascular disease. EcSOD can be upregulated in response to hypoxia and proinflammatory cytokines such as IFN-γ [38].…”

Section: Introductionmentioning

confidence: 99%

Cardiomyocyte-restricted overexpression of extracellular superoxide dismutase increases nitric oxide bioavailability and reduces infarct size after ischemia/reperfusion

et al. 2012

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Increased levels of extracellular superoxide dismutase (ecSOD) induced by preconditioning or gene therapy protect the heart from ischemia/reperfusion injury. To elucidate the mechanism responsible for this action, we studied the effects of increased superoxide scavenging on nitric oxide (NO) bioavailability in a cardiac myocyte-specific ecSOD transgenic (Tg) mouse. Results indicated that ecSOD overexpression increased cardiac myocyte-specific ecSOD activity 27.5-fold. Transgenic ecSOD was localized to the sarcolemma and, notably, the cytoplasm of cardiac myocytes. Ischemia/reperfusion injury was attenuated in ecSOD Tg hearts, in which infarct size was decreased and LV functional recovery was improved. Using the ROS spin trap, DMPO, electron paramagnetic resonance (EPR) spectroscopy demonstrated a significant decrease in ROS in Tg hearts during the first 20 min of reperfusion. This decrease in ROS was accompanied by an increase in NO production determined by EPR using the NO spin trap, Fe-MGD. Attenuated ROS in ecSOD Tg myocytes was also supported by decreased production of peroxynitrite (ONOO−). Increased NO bioavailability was confirmed by attenuated guanylate cyclase-dependent (p-VASP) signaling. In conclusion, attenuation of ROS levels by cardiac-specific ecSOD overexpression increases NO bioavailability in response to ischemia/reperfusion and protects against reperfusion injury. These findings are the first to demonstrate increased NO bioavailability with attenuation of ROS by direct measurement of these reactive species (EPR, reactive fluorescent dyes) with cardiac-specific ecSOD expression. This is also the first indication that the predominantly extracellular SOD isoform is capable of cytosolic localization that affects myocardial intracellular signal transduction and function.Electronic supplementary materialThe online version of this article (doi:10.1007/s00395-012-0305-1) contains supplementary material, which is available to authorized users.

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Extracellular-Superoxide Dismutase Type C (EC-SOD C) Reduces Myocardial Damage in Rats Subjected to Coronary Occlusion and 24 Hours of Reperfusion

Cited by 14 publications

References 35 publications

Alcohol-induced Hyperlipidemia Is Ameliorated by Orally Administered DWP208, a Sodium Succinate Form of ZYM201

Alcohol-induced Hyperlipidemia Is Ameliorated by Orally Administered DWP208, a Sodium Succinate Form of ZYM201

Superoxide Radical and Superoxide Dismutases

Cardiomyocyte-restricted overexpression of extracellular superoxide dismutase increases nitric oxide bioavailability and reduces infarct size after ischemia/reperfusion

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