Reduced vulnerability of the hypertrophied rat heart to oxygen-radical injury

1987 ◽  
Vol 65 (6) ◽  
pp. 1157-1164 ◽  
Author(s):  
Madhu Gupta ◽  
Annabel Gameiro ◽  
Pawan K. Singal
Keyword(s):  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Free Radical ◽  
Xanthine Oxidase ◽  
Oxygen Radicals ◽  
High Energy ◽  
Oxygen Radical ◽  
Similar Amount ◽  
High Energy Phosphates ◽  
Contractile Failure

Effects of xanthine – xanthine oxidase produced oxygen radicals were studied in hypertrophied rat hearts in a Langendorff preparation. Heart hypertrophy was produced by banding of the abdominal aorta for 6 weeks. This resulted in a 22% increase in ventricle/body weight ratio compared with that of sham-operated controls. Perfusion with xanthine – xanthine oxidase caused contractile failure and a significant rise in the resting tension. Complete contractile failure in hypertrophied hearts was seen at 25.5 ± 3.2 min, whereas in control hearts it happened at 14.4 ± 5.6 min. Contractile failure due to oxygen radicals in both groups was associated with a decline in high energy phosphates, increased lipid peroxidation, and extensive structural damage. Sarcolemma in both groups became permeable to the extracellular tracer lanthanum. As compared with control, in hypertrophied hearts the malondialdehyde content, indicative of lipid peroxidation, was less by 40%; whereas superoxide dismutase, a free radical scavenger, was higher by a similar amount. These data show a greater capacity of the 6-week hypertrophied heart to withstand a free radical induced contractile failure. This delay in oxygen radical effect can be partially explained by the reduced lipid peroxide content and increased superoxide dismutase activity in the hypertrophied hearts.

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 THE STATE OF THE ANTIOXIDANT SYSTEM OF THE INTERNAL ORGANS IN RATS DURING BURN DISEASE

2014 ◽  
Vol 13 (3) ◽  
pp. 51-55
Author(s):  
L. G. Netyukhailo ◽  
T. A. Sukhomlin ◽  
Ya. A. Basarab ◽  
V. V. Bondarenko ◽  
S. V. Kharchenko
Keyword(s):  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Free Radical ◽  
Salivary Glands ◽  
Antioxidant System ◽  
The State ◽  
Antioxidant Systems ◽  
Free Radical Processes ◽  
Burn Disease ◽  
Radical Processes

The objective of research was to study the state of prooxidant and antioxidant systems in the tissues of the lungs, kidneys, pancreas and salivary glands at burn disease. The intensity of the free radical processes was evaluated on the basis of the content of malondialdehyde (MDA) and antioxidant system – based on the indexes of its enzymatic chain: superoxide dismutase and catalase in homogenates of the studied organs. It has been found that changes in experimental burn disease depend on the studied organs and the stage of burn disease. The activation of free radical processes observed in all investigated organs (lungs, kidneys, pancreas and salivary glands). Reactive oxygen species induce lipid peroxidation, which is a universal marker of tissue damage. MDA appears in the body during degradation of polyunsaturated fatty acids and it’s a marker of lipid peroxidation and oxidative stress. It was found the increasing of MDA in all organs, especially in the lungs and kidneys at stage of burn shock. Under these conditions it was observed the decrease of superoxide dismutase and catalase in all investigated organs. At burn disease there is development of disbalance between the action of prooxidant and antioxidant systems due to the activation of free radical processes.

Time course of structure, function, and metabolic changes due to an exogenous source of oxygen metabolites in rat heart

1989 ◽  
Vol 67 (12) ◽  
pp. 1549-1559 ◽  
Author(s):  
Madhu Gupta ◽  
Pawan K. Singal
Keyword(s):  
Time Course ◽  
Active Oxygen Species ◽  
Lipid Peroxide ◽  
High Energy ◽  
Active Oxygen ◽  
High Energy Phosphates ◽  
Oxygen Species ◽  
Peroxide Content ◽  
Resting Tension ◽  
Contractile Failure

Effects of xanthine (2 mM) and xanthine oxidase (10 U/L) perfusion on myocardial function, lipid peroxide content, high-energy phosphates and their metabolites, and ultrastructure were examined in isolated perfused rat hearts to define the time course of myocardial injury due to exogenous supply of active oxygen species. Peak-developed force and dF/dt showed a decline within 5 min and complete contractile failure was seen at 20 min. Resting tension was higher at 10 min and reached a maximum value of 400% at 40 min. These changes in contractile parameters were reduced by superoxide dismutase (1.2 × 105 U/L), catalase (2 and 4 × 104 U/L), and mannitol (10 and 20 mM). Lipid peroxide content was significantly higher at 5 min and rose continuously with xanthine – xanthine oxidase (X–XO) perfusion. A close correlation was noted (r = 0.935) between increased lipid peroxide content and a decrease in peak-developed force. Creatine phosphate and adensoine triphosphate (ATP) showed a time-dependent decrease due to X–XO perfusion. Loss of ATP also correlated (r = 0.819) with the contractile failure. Adenosine diphosphate showed an increase at 5 min followed by a decrease at 20 and 40 min. Adenosine monophosphate, adenosine, and creatine content increased with X–XO perfusion. In a semiquantitative morphometric study, significant myocardial and vascular changes became apparent only after 10 min of X–XO perfusion. When a 5-min perfusion with X–XO was followed by a control perfusion, a recovery of developed force and normal structure was noted at 40 min. These data show that X–XO induced contractile failure involves partially reduced forms of oxygen such as superoxide, hydroxyl radicals, and hydrogen peroxide. The negative inotropic effect of a vascular supply of these active oxygen species may be related to increased lipid peroxidation as well as the loss of high-energy phosphates. Structural damage to myocytes and blood vessels and a rise in resting tension were delayed events requiring a continuous and longer exposure to radical species.Key words: myocardial failure, oxygen radicals, lipid peroxidation, myocardial high-energy phosphates, myocardial cell damage, antioxidant protection.

Oxypurinol administration fails to prevent free radical-mediated lipid peroxidation during loaded breathing

1999 ◽  
Vol 87 (3) ◽  
pp. 1123-1131 ◽  
Author(s):  
G. Supinski ◽  
D. Nethery ◽  
D. Stofan ◽  
L. Szweda ◽  
A. DiMarco
Keyword(s):  
Lipid Peroxidation ◽  
Free Radical ◽  
Xanthine Oxidase ◽  
Thiobarbituric Acid ◽  
Thiobarbituric Acid Reactive Substances ◽  
Xanthine Oxidase Inhibitor ◽  
Air Breathing ◽  
Fatigue Development ◽  
Loaded Breathing

The purpose of the present study was to determine whether it is possible to alter the development of fatigue and ablate free radical-mediated lipid peroxidation of the diaphragm during loaded breathing by administering oxypurinol, a xanthine oxidase inhibitor. We studied 1) room-air-breathing decerebrate, unanesthetized rats given either saline or oxypurinol (50 mg/kg) and loaded with a large inspiratory resistance until airway pressure had fallen by 50% and 2) unloaded saline- and oxypurinol-treated room-air-breathing control animals. Additional sets of studies were performed with animals breathing 100% oxygen. Animals were killed at the conclusion of loading, and diaphragmatic samples were obtained for determination of thiobarbituric acid-reactive substances and assessment of in vitro force generation. We found that loading of saline-treated animals resulted in significant diaphragmatic fatigue and thiobarbituric acid-reactive substances formation ( P < 0.01). Oxypurinol administration, however, failed to increase load trial time, reduce fatigue development, or prevent lipid peroxidation in either room-air-breathing or oxygen-breathing animals. These data suggest that xanthine oxidase-dependent pathways do not generate physiologically significant levels of free radicals during the type of inspiratory resistive loading examined in this study.

scholarly journals Tirilazad Pretreatment Improves Early Cerebral Metabolic and Blood Flow Recovery from Hyperglycemic Ischemia

1995 ◽  
Vol 15 (1) ◽  
pp. 88-96 ◽  
Author(s):  
Yuichi Maruki ◽  
Raymond C. Koehler ◽  
Jeffrey R. Kirsch ◽  
Kathleen K. Blizzard ◽  
Richard J. Traystman
Keyword(s):  
Lipid Peroxidation ◽  
Blood Flow ◽  
Intracranial Pressure ◽  
Intracellular Ph ◽  
High Energy ◽  
Vehicle Group ◽  
Resonance Spectroscopy ◽  
High Energy Phosphates ◽  
Early Reperfusion ◽  
Tirilazad Mesylate

Acidosis may augment cerebral ischemic injury by promoting lipid peroxidation. We tested the hypothesis that when acidosis is augmented by hyperglycemia, pretreatment with the 21-aminosteroid tirilazad mesylate (U74006F), a potent inhibitor of lipid peroxidation in vitro, improves early cerebral metabolic recovery. In a randomized, blinded study, anesthetized dogs received either tirilazad mesylate (1 mg/kg plus 0.2 mg/kg/h; n = 8) or vehicle (n = 8). Hyperglycemia (400–500 mg/dl) was produced prior to 30 min of global incomplete cerebral ischemia. Intracellular pH and high energy phosphates were measured by phosphorus magnetic resonance spectroscopy. During ischemia, microsphere-determined CBF decreased to 8 ± 4 ml min−1 100 g−1 and intracellular pH decreased to 5.6 ± 0.2 in both groups. During the first 20 min of reperfusion, ATP partially recovered in the vehicle group to 57 ± 21% of baseline, but then declined progressively in association with elevated intracranial pressure. By 30 min, ATP recovery was greater in the tirilazad group (77 ± 35 vs. 36 ± 19%), although postischemic hyperemia was similar. By 45 min, the tirilazad group had a higher intracellular pH (6.5 ± 0.5 vs. 5.9 ± 0.6) and a lower intracranial pressure (18 ± 6 vs. 52 ± 24 mm Hg). By 180 min, blood flow and ATP were undetectable in seven of eight vehicle-treated dogs, whereas ATP was >67% and pH was >6.7 in six of eight tirilazad-treated dogs. Thus, tirilazad acts during early reperfusion to prevent secondary metabolic decay associated with severe acidotic ischemia. If tirilazad acts by inhibiting lipid peroxidation, then these data are consistent with extreme acidosis limiting recovery by a mechanism involving lipid peroxidation.

Contracture and cell damage in calcium paradox is not caused by lipid peroxidation

1988 ◽  
Vol 66 (8) ◽  
pp. 1087-1091 ◽  
Author(s):  
B. Belluk ◽  
M. Gupta ◽  
P. K. Singal
Keyword(s):  
Lipid Peroxidation ◽  
Structure Function ◽  
Xanthine Oxidase ◽  
Oxygen Radicals ◽  
Cell Damage ◽  
Calcium Paradox ◽  
Rat Hearts ◽  
Malondialdehyde Content ◽  
Perfused Rat Hearts ◽  
Dose Dependent Decrease

The role of oxygen radicals and lipid peroxidation in calcium-paradox injury in isolated perfused rat hearts was studied by examining the effects of mannitol and (or) allopurinol on this phenomenon. Myocardial changes due to calcium paradox were characterized by contractile failure, a rise in resting tension, and cell damage. These changes were also accompanied by increased lipid peroxidation, as indicated by an increase in malondialdehyde content. Mannitol (an effective quencher of hydroxyl radicals) treatment resulted in a dose-dependent decrease in lipid peroxidation but did not affect other changes due to calcium paradox. Allopurinol (an inhibitor of xanthine oxidase) neither affected lipid peroxidation nor modified any of the structure–function changes due to calcium paradox. These data demonstrate the occurrence of lipid peroxidation which, however, may not be involved in the observed structure–function changes due to calcium paradox. It is also suggested that in this experimental model, xanthine oxidase may not be the inducer of oxygen radicals or of lipid peroxidation.

scholarly journals Tocotrienol-Rich Fraction Ameliorates Antioxidant Defense Mechanisms and Improves Replicative Senescence-Associated Oxidative Stress in Human Myoblasts

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Shy Cian Khor ◽  
Wan Zurinah Wan Ngah ◽  
Yasmin Anum Mohd Yusof ◽  
Norwahidah Abdul Karim ◽  
Suzana Makpol
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Free Radical ◽  
Glutathione Peroxidase ◽  
Defense Mechanisms ◽  
Antioxidant Defense ◽  
Replicative Senescence ◽  
Ros Generation ◽  
Tocotrienol Rich Fraction

During aging, oxidative stress affects the normal function of satellite cells, with consequent regeneration defects that lead to sarcopenia. This study aimed to evaluate tocotrienol-rich fraction (TRF) modulation in reestablishing the oxidative status of myoblasts during replicative senescence and to compare the effects of TRF with other antioxidants (α-tocopherol (ATF) andN-acetyl-cysteine (NAC)). Primary human myoblasts were cultured to young, presenescent, and senescent phases. The cells were treated with antioxidants for 24 h, followed by the assessment of free radical generation, lipid peroxidation, antioxidant enzyme mRNA expression and activities, and the ratio of reduced to oxidized glutathione. Our data showed that replicative senescence increased reactive oxygen species (ROS) generation and lipid peroxidation in myoblasts. Treatment with TRF significantly diminished ROS production and decreased lipid peroxidation in senescent myoblasts. Moreover, the gene expression of superoxide dismutase(SOD2), catalase(CAT),and glutathione peroxidase(GPX1)was modulated by TRF treatment, with increased activity of superoxide dismutase and catalase and reduced glutathione peroxidase in senescent myoblasts. In comparison to ATF and NAC, TRF was more efficient in heightening the antioxidant capacity and reducing free radical insults. These results suggested that TRF is able to ameliorate antioxidant defense mechanisms and improves replicative senescence-associated oxidative stress in myoblasts.

scholarly journals Oxidative status of prostate and its dynamics against etiotropic antimicrobial chemotherapy in patients with chronic bacterial prostatitis

2019 ◽  
Vol 20 (3) ◽  
pp. 56-65
Author(s):  
О. I. Bratchikov ◽  
Р. A. Dubonos ◽  
I. A. Tyuzikov
Keyword(s):  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Free Radical ◽  
Treatment Group ◽  
Positive Relationship ◽  
Pain Syndrome ◽  
Oxidative Status ◽  
Control Group ◽  
Chronic Bacterial Prostatitis ◽  
Bacterial Prostatitis

The study objective is to investigate some initial characteristics of prostate oxidative status and their dynamics during the course of etiotropic antimicrobial monochemotherapy in patients with chronic bacterial prostatitis (CBP).Materials and methods. The work is based on treatment of 90 men aged 24–46 years (mean age 38.2 ± 1.4 years) with CBP (the treatment group), and 30 clinically healthy men aged 20–45 years (mean age 35.5 ± 1.5 years) (control group). All men underwent the same type of comprehensive examination during the study, and the results of the examination of the men of the control group were taken as reference values of the conditional norm. Complaints and anamnesis were collected. General physical, special urological, microbiological, laboratory, sonographic studies were performed. The etiotropic antimicrobial monochemotherapy was selected according to the results of microbiological studies of the secretion of the prostate gland, and levofloxacin (500 mg within 28 days) was chosen as a base drug for the subgroup of treatment (n = 15) isolated from the treatment group in the 2nd stage of the study. To assess the characteristics of the prostate oxidative status and its dynamics during etiotropic antimicrobial monochemotherapy, various modifications of biochemical studies of the secretion of the prostate were performed (reactive oxygen species (ROS), lipid peroxidation products (diol conjugates, malonic dialdehyde), activity of superoxide dismutase).Results. In patients with CBP in the secretion of the prostate due to increased ROS formation, increased functional activity (free radical aggression), increased reactions of lipid peroxidation and increased functional load on prostatic superoxide dismutase. Antimicrobial monochemotherapy of CBP was characterized by a microbiological efficacy of 86.7 % and was accompanied by a positive dynamics of a number of clinical and laboratory parameters of chronic bacterial prostatitis, however, this did not lead to the complete elimination of pain syndrome and oxidative disorders in the secretion of the prostate, and also did not significantly improve the quality life of patients and prostate secretory function. In patients with CBP a significant positive relationship was found between the amount of ROS and superoxide dismutase activity in the secretion of the prostate (n = 90; r = 0.413; p = 0.001); and the positive relationship between the amount of ROS in the secretion of the prostate and the clinical pain index (n = 90, r = 0.304, p = 0.001), which reflected the essential role of free radical prostatic aggression as an non-infectious component of the multifactorial pathogenesis of the pain syndrome in CBP.Conclusion. The persistence of residual oxidative disorders and functional deficits in the prostate after a standard course of microbial monochemotherapy justifies the advisability of the additional administration of antioxidants and antihypoxic agents in CBP. 

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