Adriamycin-induced myocardial dysfunction in vitro is mediated by free radicals

The role of free radicals in adriamycin (Adr)-induced acute myocardial changes was examined by using different antioxidants. Exposure of papillary muscles to Adr (100 microM) in a tissue bath for 60 min reduced developed force by 42%, increased lipid peroxidation by 200%, and resulted in characteristic ultrastructural changes. Catalase (4 x 10(4) U/l), an enzyme effective in the hydrolysis of hydrogen peroxide (H2O2), was more effective in maintaining the developed force than mannitol (20 mM), a hydroxyl radical scavenger. A small protection of developed force seen with superoxide dismutase (1.2 x 10(5) U/l), a quencher of superoxide radical, was evident for the first 15 min only. Only catalase and mannitol showed significant protection against Adr-induced increase in lipid peroxidation. Ultrastructural changes due to Adr alone included mitochondrial swelling, intramitochondrial granules, vacuolization, and disruption of sarcomeres. All of these changes were reduced in the presence of both catalase and mannitol, whereas superoxide dismutase was without any effect. Complete structural or functional protection was not seen with any of the antioxidants used in the study. Although both H2O2 and hydroxyl radical appear to be involved in Adr-induced deleterious effects, data on developed force also indicate that H2O2 may have a major role in mediating the acute effects of Adr in vitro.

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Diabetes-induced endothelial dysfunction in streptozotocin-treated rats: role of prostaglandin endoperoxides and free radicals.

Journal of the American Society of Nephrology ◽

10.1681/asn.v461327 ◽

1993 ◽

Vol 4 (6) ◽

pp. 1327-1336

Author(s):

F X Dai ◽

A Diederich ◽

J Skopec ◽

D Diederich

Keyword(s):

Free Radicals ◽

Endothelial Dysfunction ◽

Diabetic Rats ◽

Renal Arteries ◽

Radical Scavenger ◽

Wistar Kyoto ◽

And Control ◽

A2 Receptors

The vasoactive responses of renal arteries from diabetic and control rats were compared in vitro in arteriograph assemblies. Diabetes was established by an iv injection of streptozotocin (55 mg/kg) in Wistar-Kyoto rats. Endothelium-dependent relaxations mediated by nitric oxide (EDNO) were impaired in arteries from the diabetic rats; the impairment in endothelial function increased with duration of the diabetic state. After 6 and 16 wk, the concentrations of acetylcholine required to produce 50% relaxation of norepinephrine preconstriction were 3.2 and 25 microM for arteries from diabetic rats and 0.4 microM in control arteries, representing 8- and 62-fold decreases in sensitivity to the endothelium-dependent vasodilator in the diabetic arteries. After 6 wk of diabetes, renal arteries also became 20-fold less sensitive to relaxation induced by histamine, another agonist that induces EDNO-mediated relaxations. The inhibition of EDNO production with L-NG-nitroarginine produced greater impairments in acetylcholine relaxations in arteries from diabetic rats than from control rats. Relaxations in response to acetylcholine were impaired in arteries from diabetic rats because of increased production of factors that opposed the vasorelaxant effects of EDNO, rather than from decreased production of EDNO. Pretreatment of the diabetic arteries with the hydroxyl radical scavenger dimethylthiourea normalized relaxations in response to acetylcholine. The blockade of prostaglandin H2-thromboxane A2 receptors with SQ 29548 also improved relaxations in response to acetylcholine in diabetic arteries. These data indicate that endothelial dysfunction in the renal arteries of diabetic rats may be mediated by the increased production of free radicals and of prostaglandin endoperoxides, which oppose the vasorelaxant effects of EDNO.

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Mechanisms of oxidative stress in porcine oocytes and the role of anti-oxidants

Reproduction Fertility and Development ◽

10.1071/rd08037 ◽

2008 ◽

Vol 20 (6) ◽

pp. 694 ◽

Cited By ~ 28

Author(s):

B. D. Whitaker ◽

J. W. Knight

Keyword(s):

Oxidative Stress ◽

Superoxide Dismutase ◽

Free Radicals ◽

Dna Fragmentation ◽

Reduced Glutathione ◽

Sod Activity ◽

Anti Oxidant ◽

Gpx Activity

The mechanisms of oxidative stress in in vitro maturing porcine oocytes and the effects of anti-oxidant supplementation of the medium in ameliorating these effects were investigated in the present study. In addition to intracellular reduced glutathione (GSH) concentrations and DNA fragmentation, the present study focused on superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase activity. The anti-oxidants used were N-acetylcysteine (NAC) and its derivative NAC-amide (NACA). The results indicate that when SOD is inhibited, supplementation of the maturarion medium with 1.5 mm NAC or NACA compensates for the decrease in SOD activity by reducing the degree of DNA fragmentation (P < 0.05). When GPx is inhibited, supplementation of the maturarion medium with 1.5 mm NAC alleviates the effects of no GPx activity, as indicated by a decrease in the degree of DNA fragmentation (P < 0.05). When the maturarion medium was supplemented with 1.5 mm NACA, intracellular GSH concentrations decreased (P < 0.05) and SOD and catalase activities increased (P < 0.05) along with the degree of DNA fragmentation. These results indicate that the mechanisms of alleviating oxidative stress in porcine oocytes are very complex and supplementing maturing oocytes with anti-oxidants may enhance enzyme activities and eliminate free radicals.

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Phenolic constituents and inhibitory effects of the leaf of Rauvolfia vomitoria Afzel on free radicals, cholinergic and monoaminergic enzymes in rat’s brain in vitro

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2020-0144 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Olubukola H. Oyeniran ◽

Adedayo O. Ademiluyi ◽

Ganiyu Oboh

Keyword(s):

Lipid Peroxidation ◽

Free Radicals ◽

Methanolic Extract ◽

Array Detector ◽

Oh Radicals ◽

Inhibitory Effects ◽

Methanolic Extracts ◽

Phenolic Constituents ◽

Rauvolfia Vomitoria

AbstractObjectivesRauvolfia vomitoria is a medicinal plant used traditionally in Africa in the management of several human diseases including psychosis. However, there is inadequate scientific information on the potency of the phenolic constituents of R. vomitoria leaf in the management of neurodegeneration. Therefore, this study characterized the phenolic constituents and investigated the effects of aqueous and methanolic extracts of R. vomitoria leaf on free radicals, Fe2+-induced lipid peroxidation, and critical enzymes linked to neurodegeneration in rat’s brain in vitro.MethodsThe polyphenols were evaluated by characterizing phenolic constituents using high-performance liquid chromatography coupled with diode array detector (HPLC-DAD). The antioxidant properties were assessed through the extracts ability to reduce Fe3+ to Fe2+; inhibit ABTS, DPPH, and OH radicals and Fe2+-induced lipid peroxidation. The effects of the extracts on AChE and MAO were also evaluated.ResultsThe phenolic characterization of R. vomitoria leaf revealed that there were more flavonoids present. Both aqueous and methanolic extracts of R. vomitoria leaf had inhibitory effects with the methanolic extract having higher significant (p≤0.05) free radicals scavenging ability coupled with inhibition of monoamine oxidases. However, there was no significant (p≤0.05) difference obtained in the inhibition of lipid peroxidation and cholinesterases.ConclusionThis study suggests that the rich phenolic constituents of R. vomitoria leaf might contribute to the observed antioxidative and neuroprotective effects. The methanolic extract was more potent than the aqueous extract; therefore, extraction of R. vomitoria leaf with methanol could offer better health-promoting effects in neurodegenerative condition.

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4-Hydroxynonenal Contributes to Fibroblast Senescence in Skin Photoaging Evoked by UV-A Radiation

Antioxidants ◽

10.3390/antiox10030365 ◽

2021 ◽

Vol 10 (3) ◽

pp. 365 ◽

Cited By ~ 1

Author(s):

Audrey Swiader ◽

Caroline Camaré ◽

Paul Guerby ◽

Robert Salvayre ◽

Anne Negre-Salvayre

Keyword(s):

Lipid Peroxidation ◽

Dermal Fibroblasts ◽

Connective Tissues ◽

Hairless Mice ◽

Cultured Fibroblasts ◽

Γh2ax Foci ◽

Skin Photoaging ◽

Actinic Elastosis

Solar ultraviolet A (UV-A) radiation promotes a huge variety of damages on connective tissues and dermal fibroblasts, including cellular senescence, a major contributor of skin photoaging. The mechanisms of skin photoaging evoked by UV-A partly involve the generation of reactive oxygen species and lipid peroxidation. We previously reported that 4-hydroxynonenal (HNE), a lipid peroxidation-derived aldehyde, forms adducts on elastin in the skins of UV-A irradiated hairless mice, possibly contributing to actinic elastosis. In the present study, we investigated whether and how HNE promotes fibroblast senescence in skin photoaging. Dermal fibroblasts of skins from UV-A-exposed hairless mice exhibited an increased number of γH2AX foci characteristic of cell senescence, together with an accumulation of HNE adducts partly colocalizing with the cytoskeletal protein vimentin. Murine fibroblasts exposed to UV-A radiation (two cycles of 15 J/cm2), or HNE (30 µM, 4 h), exhibited senescence patterns characterized by an increased γH2AX foci expression, an accumulation of acetylated proteins, and a decreased expression of the sirtuin SIRT1. HNE adducts were detected on vimentin in cultured fibroblasts irradiated by UV-A or incubated with HNE. The HNE scavenger carnosine prevented both vimentin modification and fibroblast senescence evoked by HNE in vitro and in the skins of UV-A-exposed mice. Altogether, these data emphasize the role of HNE and lipid peroxidation-derived aldehydes in fibroblast senescence, and confirm the protective effect of carnosine in skin photoaging.

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Ethane production as a measure of lipid peroxidation after renal ischemia

AJP Renal Physiology ◽

10.1152/ajprenal.1986.251.5.f839 ◽

1986 ◽

Vol 251 (5) ◽

pp. F839-F843 ◽

Cited By ~ 1

Author(s):

M. S. Paller ◽

R. P. Hebbel

Keyword(s):

Lipid Peroxidation ◽

Free Radicals ◽

Superoxide Radical ◽

Oxygen Free Radicals ◽

Tissue Injury ◽

Renal Ischemia ◽

Radical Scavenger ◽

Base Line ◽

Ethane Production

After renal ischemia, oxygen free radicals are formed and produce tissue injury, in large part, through peroxidation of polyunsaturated fatty acids. We used an in vivo method to monitor lipid peroxidation after renal ischemia, the measurement of ethane in expired gas, to determine the time course of lipid peroxidation and the effect of several agents to limit lipid peroxidation after renal ischemia. In anesthetized rats there was no significant increase in ethane production during 60 min of renal ischemia. During the first 10 min of renal reperfusion, there was a prompt increase in ethane production from 2.9 +/- 1.3 to 6.3 +/- 1.9 pmol/min (P less than 0.05). Ethane production was significantly increased during the first 50 min of reperfusion and then rapidly tapered to base-line levels. Preischemic administration of allopurinol to prevent superoxide radical generation or the superoxide radical scavenger superoxide dismutase prevented the increase in ethane production during postischemic reperfusion. These studies confirm that there is increase lipid peroxidation following renal ischemia that can be prevented by agents which limit the formation or accumulation of oxygen free radicals. This in vivo method for measuring lipid peroxidation could also be employed to study the effects of ischemia on lipid peroxidation in other organs, as well as to monitor lipid peroxidation in other forms of injury.

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Role of Free Radicals and Lipid Peroxidation in Gastric Mucosal Injury Induced by Ischemia-Reperfusion in Rats

Scandinavian Journal of Gastroenterology ◽

10.3109/00365528909091124 ◽

1989 ◽

Vol 24 (sup162) ◽

pp. 55-58 ◽

Cited By ~ 27

Author(s):

S. Ueda ◽

T. Yoshikawa ◽

S. Takahashi ◽

H. Ichikawa ◽

M. Yasuda ◽

...

Keyword(s):

Lipid Peroxidation ◽

Free Radicals ◽

Ischemia Reperfusion ◽

Mucosal Injury ◽

Gastric Mucosal Injury

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Organic Peroxy Free Radicals and the Role of Superoxide Dismutase and Antioxidants

Reactive Oxygen Species in Chemistry, Biology, and Medicine ◽

10.1007/978-1-4757-0417-4_5 ◽

1988 ◽

pp. 81-84

Author(s):

R. L. Willson

Keyword(s):

Superoxide Dismutase ◽

Free Radicals

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

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1992.262.3.h806 ◽

1992 ◽

Vol 262 (3) ◽

pp. H806-H812 ◽

Cited By ~ 5

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.

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