Free-radical scavengers, thiol-containing reagents and endothelium-dependent relaxation in isolated rat and human resistance arteries

1993 ◽  
Vol 84 (3) ◽  
pp. 287-295 ◽  
Author(s):  
W. Sunman ◽  
A.D. Hughes ◽  
P.S. Sever
Keyword(s):  
Superoxide Dismutase ◽  
Free Radical ◽  
Methyl Ester ◽  
Enzyme Inhibitor ◽  
Subcutaneous Fat ◽  
Free Radical Scavengers ◽  
Radical Scavenger ◽  
Resistance Arteries ◽  
Rat Mesentery ◽  
Endothelium Dependent Relaxation

1. Small arteries were isolated from either rat mesentery or human subcutaneous fat, and mounted in a myograph for the measurement of isometric force. 2. Superoxide dismutase, either in the presence or absence of catalase, relaxed noradrenaline-induced tone. This effect was abolished by removal of the endothelium or incubation with an inhibitor of NO synthase, N-ω-nitro-L-arginine methyl ester. Catalase alone had a negligible effect on noradrenaline-induced tone. 3. Captopril, an angiotensin-converting enzyme inhibitor and putative free-radical scavenger, did not relax pre-contracted isolated vessels. N-Acetylcysteine caused an endothelium-independent relaxation of rat vessels. Similar effects were observed in human vessels. 4. Acetylcholine induced a concentration-dependent relaxation of isolated resistance arteries, which was inhibited by removal of the endothelium or N-ω-nitro-L-arginine methyl ester, but unaffected by indomethacin. Preincubation with captopril, N-acetylcysteine or catalase alone did not alter the acetylcholine concentration-response relationship, but superoxide dismutase in combination with catalase enhanced responses to acetylcholine, causing a six-fold increase in potency. 5. Superoxide dismutase causes endothelium-dependent relaxation of resistance arteries and potentiates responses to acetylcholine. This action is probably due to the ability of the enzyme to scavenge superoxide anions which inhibit endothelium-dependent relaxation. 6. N-Acetylcysteine causes an endothelium-independent relaxation of resistance arteries which is probably unrelated to the putative ability of this compound to scavenge superoxide radicals and may reflect a direct action on vascular smooth muscle.

Cerebral vascular responsiveness after experimental traumatic brain injury: the beneficial effects of delayed hypothermia combined with superoxide dismutase administration

2008 ◽  
Vol 109 (3) ◽  
pp. 502-509 ◽  
Author(s):  
Anna I. Baranova ◽  
Enoch P. Wei ◽  
Yuji Ueda ◽  
Milton M. Sholley ◽  
Hermes A. Kontos ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Superoxide Dismutase ◽  
Free Radical ◽  
Brain Injury ◽  
Vascular Function ◽  
Free Radical Scavengers ◽  
Therapeutic Window ◽  
Radical Scavenger ◽  
Vascular Protection ◽  
Cerebral Vascular

Object Traumatic brain injury (TBI) induces cerebral vascular dysfunction reflected in altered responses to vasodilators such as acetylcholine and hypercapnia. It has been demonstrated that the use of either posttraumatic hypothermia or free radical scavengers offered vascular protection when those treatments were delivered early after the injury, losing efficacy when the initiation of either treatment was delayed. Because immediate posttraumatic treatment is not realistic in the clinical setting, the authors undertook this study to investigate whether the combination of delayed hypothermia and the delayed administration of the free radical scavenger superoxide dismutase (SOD) could result in improved vascular protection. Methods Male Sprague–Dawley rats were anesthetized and subjected to either an impact-acceleration or sham injury. Animals were treated either with hypothermia (32°C) initiated 60 minutes after TBI, delayed SOD (60 U/ml) applied 90 minutes after TBI, or a combination of delayed hypothermia (32°C) and delayed SOD (60 U/ml) applied 15 minutes prior to the cessation of hypothermia. In this investigation, the diameter of cerebral pial arterioles was measured at rest and then challenged with vasodilator acetylcholine and hypercapnia. Four vessels were assessed per animal prior to injury and then again up to 6 hours after injury. Results Delayed SOD treatment did not enhance vascular function, while delayed hypothermia treatment only partially preserved pial vascular function. However, the combination of delayed hypothermia and delayed SOD significantly preserved vascular function after the injury. Conclusions The results of these studies demonstrate that delayed hypothermia partially preserves vascular function after TBI, while expanding the therapeutic window over which agents such as SOD can now provide enhanced protection.

Oxygen free radical-mediated selective endothelial dysfunction in isolated coronary artery

1992 ◽  
Vol 262 (3) ◽  
pp. H806-H812 ◽  
Author(s):  
K. Todoki ◽  
E. Okabe ◽  
T. Kiyose ◽  
T. Sekishita ◽  
H. Ito
Keyword(s):  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Free Radicals ◽  
Free Radical ◽  
Coronary Artery ◽  
Iron Chelator ◽  
Oxygen Free Radical ◽  
Alpha Tocopherol ◽  
Endothelium Dependent Relaxation ◽  
Iron Chelator Deferoxamine

To understand the direct involvement of free radicals causing reduction in endothelium-dependent relaxation of isolated canine coronary ring preparations, this study was undertaken to examine the effect of free radicals generated from dihydroxy fumarate (DHF) plus Fe(3+)-ADP or from H2O2 plus FeSO4. The vasodilators (acetylcholine, bradykinin, A23187, and nitroglycerin) were given after DHF/Fe(3+)-ADP or H2O2/FeSO4 was removed from the organ chamber. The earlier DHF/Fe(3+)-ADP exposure produced an attenuation of the relaxation of the rings induced by acetylcholine, bradykinin, or A23187 but not of the relaxation induced by nitroglycerin. The observed effect of previous DHF/Fe(3+)-ADP exposure was significantly protected in the vessels isolated from the dogs treated with alpha-tocopherol. In the experiments for assessing the effect of various scavengers, 1O2 scavenger histidine or iron chelator deferoxamine effectively protected the attenuation induced by DHF/Fe(3+)-ADP exposure of the relaxation elicited by acetylcholine; superoxide dismutase (SOD), catalase, or dimethyl sulfoxide (DMSO) had no effect on this system. Furthermore, the relaxation elicited by acetylcholine, but not nitroglycerin, was significantly attenuated by the earlier exposure to .OH generated by Fenton's reagent (H2O2+FeSO4); the attenuation was significantly protected by DMSO. These results are consistent with the view that .OH, 1O2, and/or iron-dependent reactive species selectively damage endothelium-dependent relaxation as opposed to endothelium-independent relaxation in endothelium-intact coronary ring preparations. It is also postulated that lipid peroxidation may be responsible for this effect.

scholarly journals Bioimmunological responses to Schistosoma mansoni and Fasciola gigantica worm homogenates either with or without saponin

2010 ◽  
Vol 4 (05) ◽  
pp. 334-344
Author(s):  
Amany Sayed Maghraby ◽  
Manal Abdel-Aziz Hamed ◽  
Sanaa Ahmed Ali
Keyword(s):  
Free Radical ◽  
Liver Function ◽  
Schistosoma Mansoni ◽  
Subcutaneous Administration ◽  
Free Radical Scavenger ◽  
Fasciola Gigantica ◽  
Free Radical Scavengers ◽  
Radical Scavenger ◽  
Immune Mediated ◽  
Mice Liver

Background: In this study, we evaluated the biochemical, immunological, histopathological and antischistosomal activities of Schistosoma mansoni or Fasciola gigantica worm homogenates mixed either with or without saponin that was extracted from Atriplex nummularia. Methodology: The immunization schedule was based on subcutaneous administration of two doses (50 μg /100 μl PBS) of each homogenate with time intervals of 15 days. After 15 days of the last homogenate inoculation, all mice were challenged with 100 Schistosoma mansoni cercariae and sacrificed after two months. Free radical scavengers and liver function enzymes were determined in mice liver. Worm counting and the histopathological picture of the liver were also done. Results: Immunization with Schistosoma or Fasciola worm homogenates, mixed either with or without saponin, recorded an amelioration of the free radical scavenger levels, liver function enzymes and reduction in worm burden, as well as improvement of the histological feature of the liver, the number and size of granuloma, evidence of increased immune reaction manifested by a lymphocytic cuff surrounding the granuloma, diminution of its fibrotic and collagen content, and destruction of Schistosoma ova. Conclusion: Fasciola or Schistosoma worm antigens mixed with or without saponin succeeded to eliminate the product of oxidative stress and assistance in immune-mediated destruction of eggs that ameliorate the histopathological picture of the liver cells and preserve its function.

scholarly journals Bergenin Content and Free Radical Scavenging Activity of Bergenia Extracts

2015 ◽  
Vol 10 (7) ◽  
pp. 1934578X1501000
Author(s):  
Helena Hendrychová ◽  
Jan Martin ◽  
Lenka Tůmová ◽  
Nina Kočevar-Glavač
Keyword(s):  
Free Radical ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Hplc Method ◽  
Free Radical Scavenging ◽  
Free Radical Scavenging Activity ◽  
Free Radical Scavengers ◽  
Radical Scavenger ◽  
Scavenging Activity ◽  
Different Seasons

Our research was focused on the evaluation of bergenin content and free radical scavenging activity of extracts prepared from three different species of Bergenia - B. crassifolia (L.) Fritsch., B. ciliata (Haw.) Sternb. and B. x ornata Stein. collected during different seasons. Using an HPLC method, the highest total amount of bergenin was revealed in the leaves of B. x ornata and B. crassifolia (4.9 - 5.1 mg.g−1). Free radical scavenging power was determined by two methods - FRAP and NADH. The best free radical scavengers were B. crassifolia (FRAP: 6.7 - 15.9 mg GAE.100g−1; NADH: 20.3 - 50.9%) and B. ornata (FRAP: 13.7 - 15.2 mg GAE.100g−1; NADH: 29.3 - 31.1%). The lowest content of bergenin and the weakest radical scavenger was B. ciliata (bergenin: 3.1 mg.g−1; FRAP: 5.5 - 11.0 mg GAE.100g−1; NADH: 23.2 - 25.6%). The presence of a large percentage of bergenin is responsible for the radical scavenging activity, as shown by the results from the FRAP and NADH assays. Significant, positive correlation was found between bergenin content and radical scavenging activity in both methods.

scholarly journals Induction of heme oxygenase-1 by hypoxia and free radicals in human dermal fibroblasts

2000 ◽  
Vol 278 (1) ◽  
pp. C92-C101 ◽  
Author(s):  
Maria V. Panchenko ◽  
Harrison W. Farber ◽  
Joseph H. Korn
Keyword(s):  
Free Radicals ◽  
Free Radical ◽  
Heme Oxygenase ◽  
Iron Homeostasis ◽  
Dermal Fibroblasts ◽  
Skin Fibroblasts ◽  
Free Radical Scavengers ◽  
Radical Scavenger ◽  
Heme Oxygenase 1

Heme oxygenase-1 (HO-1) catalyzes the rate-limiting step in heme catabolism and presumably is involved in cellular iron homeostasis. It is induced by a variety of cellular stresses, including oxygen deprivation and free radical-mediated stress. We examined induction of HO-1 mRNA in skin fibroblasts and investigated the mechanism by which it occurs. Hypoxia did not appear to act via induction of oxygen free radicals: induction of HO-1 was not sensitive to the free radical scavenger GSH or other antioxidants. Moreover, hypoxia did not increase steady-state levels of free radicals generated by fibroblasts. In contrast, HO-1 induction by the oxidants, H2O2and carbonyl cyanide m-chlorophenylhydrazone (CCCP) was significantly attenuated in the presence of free radical scavengers. This correlated with increased levels of free radical production in fibroblasts treated with these oxidants. Iron depletion by desferrioxamine mesylate, a specific iron complexon, completely inhibited hypoxic stimulation of HO-1 but did not attenuate the effect of H2O2and CCCP on HO-1 mRNA. Addition of Fe2+, Fe3+, or holo-transferrin to fibroblasts increased levels of HO-1 mRNA. Treatment of cells with hypoxia, but not H2O2or an exogenous source of iron, significantly increased the half-life of HO-1 mRNA. The data suggest hypoxia regulates HO-1 gene expression by a specific posttranscriptional mechanism: stabilization of mRNA. Hypoxia has previously been shown to increase fibroblast collagen synthesis and is thought to play a role in pathogenesis of systemic sclerosis (SSc). Skin fibroblasts isolated from patients with SSc demonstrated significantly stronger induction of HO-1 by hypoxia than did fibroblasts from normal controls. We hypothesize that exposure of SSc fibroblasts to hypoxic conditions leads to in vivo selective proliferation of cells that adapt to hypoxia.

Diabetic human platelets release a substance that inhibits platelet-mediated vasodilation

1997 ◽  
Vol 273 (1) ◽  
pp. H371-H379 ◽  
Author(s):  
H. J. Oskarsson ◽  
T. G. Hofmeyer
Keyword(s):  
Superoxide Dismutase ◽  
Free Radical ◽  
Thromboxane A2 ◽  
Human Platelets ◽  
Free Radical Scavengers ◽  
Radical Scavengers ◽  
Short Acting ◽  
Vasodilatory Response ◽  
Dilatory Response ◽  
A2 Receptors

This study was performed to investigate the mechanism for impaired vasodilation in response to activated diabetic human platelets. As observed previously, diabetic platelets failed to cause vasorelaxation, whereas normal platelets produced normal vasodilation. However, when activated and perfused through quiescent, NG-nitro-L-arginine-pretreated arteries, diabetic and normal platelets caused similar degrees of vasoconstriction. Inhibition of serotonergic and thromboxane A2 receptors in preconstricted normal arteries also failed to improve vasodilatory responses to diabetic platelets. The amount of ADP released into the supernatant from activated diabetic and normal platelets was similar. Concomitant perfusion of activated diabetic platelets impaired vasodilation produced by abluminally applied acetylcholine but perfusion of normal platelets did not. Whereas activated diabetic platelets failed to produce vasodilation, supernatant from the same platelets caused normal vasorelaxation. Dimethylthiourea and Tiron, intracellular free radical scavengers, normalized the vasodilatory response to diabetic platelets, whereas superoxide dismutase, catalase, and mannitol did not. We conclude that the impaired vasorelaxation in response to activated diabetic platelets is caused by an unidentified, short-acting, platelet-derived substance(s) that interferes with the normal dilatory response.

Sign in / Sign up

Export Citation Format

Share Document