Superoxide dismutase protects against paraquat-mediated dioxygen toxicity and mutagenicity: studies in Salmonella typhimurium

1982 ◽  
Vol 60 (11) ◽  
pp. 1367-1373 ◽  
Author(s):  
Hosni M. Hassan ◽  
Carmella S. Moody
Keyword(s):  
Superoxide Dismutase ◽  
Free Radicals ◽  
Salmonella Typhimurium ◽  
Normal Level ◽  
Ames Test ◽  
Superoxide Radical ◽  
Oxygen Free Radicals ◽  
Chromosomal Breaks ◽  
Oxygen Sensitive ◽  
Mutagenic Effects

Paraquat is univalently reduced to the relatively stable, but oxygen-sensitive, paraquat radical (PQ∙+). This PQ∙+ can react with dioxygen to generate the superoxide radical, which can further generate other more deleterious species of oxygen free radicals (i.e., hydroxyl radical, OH∙). These oxygen free radicals are known to cause chromosomal breaks; therefore, it was logical to postulate that paraquat is a mutagen. This proved to be the case when tested in a modified Ames test using a liquid incubation assay. Salmonella typhimurium strains TA98 and TA100 were grown in the presence of various concentrations of PQ, as well as in the presence of known mutagenic compounds: mitomycin C, azide, and proflavine. Paraquat was much more toxic and mutagenic in a simple nutritionally restricted medium than in a rich complex medium and these toxic and mutagenic effects were oxygen dependent. Furthermore, cells containing high levels of superoxide dismutase were more resistant to the toxic and mutagenic effects of paraquat than were cells containing a normal level of this enzyme.

Ethane production as a measure of lipid peroxidation after renal ischemia

1986 ◽  
Vol 251 (5) ◽  
pp. F839-F843 ◽  
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.

Beneficial actions of superoxide dismutase and catalase in stunned myocardium of dogs

1986 ◽  
Vol 250 (3) ◽  
pp. H372-H377 ◽  
Author(s):  
G. J. Gross ◽  
N. E. Farber ◽  
H. F. Hardman ◽  
D. C. Warltier
Keyword(s):  
Blood Flow ◽  
Superoxide Dismutase ◽  
Free Radicals ◽  
Oxygen Free Radicals ◽  
Ischemia Reperfusion ◽  
Free Radical Scavengers ◽  
Stunned Myocardium ◽  
Regional Myocardial Blood Flow ◽  
Control Group ◽  
Myocardial Segment

Recent evidence suggests that oxygen free radicals may partially mediate irreversible ischemia-reperfusion injury in the myocardium. In the present study, the effect of a combination of two oxygen free radical scavengers, superoxide dismutase plus catalase (SOD + CAT), on the recovery of subendocardial segment function following 15 min of coronary artery occlusion followed by 3 h of reperfusion ("stunned" myocardium) was compared with a control group in barbital-anesthetized dogs. Myocardial segment shortening (%SS) in the subendocardium of nonischemic and ischemic areas was measured by sonomicrometry and regional blood flow by radioactive microspheres. SOD and CAT were infused into the left atrium 30 min before and throughout the occlusion period. Compared with the control group, %SS in the subendocardium of the ischemic region was significantly (P less than 0.05) greater in the SOD plus CAT-treated group during occlusion and throughout reperfusion. Since there were no significant differences in hemodynamics or regional myocardial blood flow between the SOD plus CAT and the control groups, these results suggest that toxic oxygen free radicals may be partially involved in the reversible ischemic injury that occurs during short periods of coronary occlusion followed by reperfusion.

Oxidative Stress in Critically Ill Patients

2002 ◽  
Vol 11 (6) ◽  
pp. 543-551 ◽  
Author(s):  
Caryl Goodyear-Bruch ◽  
Janet D. Pierce
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Superoxide Dismutase ◽  
Free Radicals ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Oxygen Free Radicals ◽  
Oxygen Species ◽  
Defense System ◽  
Oxygen Derived Free Radicals

Oxygen-derived free radicals play an important role in the development of disease in critically ill patients. Normally, oxygen free radicals are neutralized by antioxidants such as vitamin E or enzymes such as superoxide dismutase. However, in patients who require intensive care, oxygen free radicals become a problem when either a decrease in the removal or an overproduction of the radicals occurs. This oxidative stress and the damage due to it have been implicated in many diseases in critically ill patients. Many drugs and treatments now being investigated are directed toward preventing the damage from oxidative stress. The formation of reactive oxygen species, the damage caused by them, and the body’s defense system against them are reviewed. New interventions are described that may be used in critically ill patients to prevent or treat oxidative damage.

Effect of Oxygen Free Radicals on Cardiac Contractile Activity and Sarcolemmal Na+–Ca2+ Exchange

1996 ◽  
Vol 1 (3) ◽  
pp. 211-217
Author(s):  
Taku Matsubara ◽  
Naranjan S. Dhalla
Keyword(s):  
Superoxide Dismutase ◽  
Free Radicals ◽  
Xanthine Oxidase ◽  
Cardiac Dysfunction ◽  
Oxygen Free Radicals ◽  
Contractile Activity ◽  
Contractile Force ◽  
Cardiac Contractile ◽  
Intracellular Ca ◽  
Exchange Activity

Background Although oxygen free radicals have been shown to induce myocardial cell damage and cardiac dysfunction, the exact mechanism by which these radicals affect the heart function is not clear. Since the occurrence of intracellular Ca2+ overload is critical in the genesis of cellular damage and cardiac dysfunction, and since the sarcolemmal Na+–Ca2+ exchange is intimately involved in Ca2+ movements in myocardium, this study was undertaken to examine the effects of oxygen free radicals on the relationship between changes in cardiac contractile force development and sarcolemmal Na+–Ca2+ exchange activity. Methods and Results Isolated rat hearts were perfused with a medium containing xanthine plus xanthine oxidase for different times, and changes in contractile force as well as sarcolemmal Na+–Ca2+ exchange activity were monitored. Perfusion of the heart with xanthine plus xanthine oxidase resulted in a transient increase followed by a marked decrease in contractile activity; the resting tension was markedly increased. The xanthine plus xanthine oxidase-induced depression in developed tension, rate of contraction, and rate of relaxation, except the transient increase in contractile activity, was prevented by the addition of catalase, but not by superoxide dismutase, in the perfusion medium. A time-dependent depression in sarcolemmal Na+–Ca2+ was also evident upon perfusing the heart with xanthine plus xanthine oxidase. This depression in Na+-dependent Ca2+ uptake was associated with a decrease in the maximal velocity of reaction without any changes in the affinity of Na+–Ca2+ exchanger for Ca2+. The presence of catalase, unlike superoxide dismutase, prevented the decrease in sarcolemmal Na+–Ca2+ exchange activity in hearts perfused with xanthine plus xanthine oxidase. Conclusion The results support the view that a depression in the sarcolemmal Na+–Ca2+ exchange activity may contribute to the occurrence of intracellular Ca2+ overload and subsequent decrease in contractile activity. Furthermore, these actions of xanthine plus xanthine oxidase in the whole heart appear to be a consequence of H2O2 production rather than the ‘ generation of superoxide radicals.

scholarly journals Genotoxicity of triiodothyronine: Effects on Salmonella typhimurium TA100 and human lymphocytes in vitro

Genetika ◽  
2017 ◽  
Vol 49 (2) ◽  
pp. 387-397
Author(s):  
Jasna Bosnjak-Neumüller ◽  
Ninoslav Djelic ◽  
Milena Radakovic ◽  
Stoimir Kolarevic ◽  
Dragana Mitic-Culafic ◽  
...  
Keyword(s):  
Salmonella Typhimurium ◽  
Mammalian Cells ◽  
Ames Test ◽  
Human Lymphocytes ◽  
Genetic Material ◽  
Genotoxic Effects ◽  
Reverse Mutation ◽  
Mutagenic Effects ◽  
Mutation Assay

There is increasing evidence that substances which are normally present in human or animal bodies may, under the certain circumstances, exhibit deleterious effects on genetic material, therefore acting as endogenous mutagenic agents. Since hormones represent one of the best studied endogenous mutagens, some research focused on the possible role of thyroid hormone in mutagenesis and carcinogenesis. Indeed, thyroid hormones accelerate aerobic metabolism and production of reactive oxygen species (ROS) and, therefore, may exhibit mutagenic effects in various test systems on mammalian cells. However, possible mutagenic effects on prokaryotic DNA has not been investigated so far. Hence, the aim of this research was to compare the sensitivity of TA 100 Salmonella typhimurium with and without metabolic activation with S9 fraction, and human lymphocytes to possible genotoxic effects of triiodothyronine (T3). Therefore, we used the reverse mutation assay on S. typhimurium (Ames test) and in vitro Comet assay in isolated peripheral blood human lymphocytes. In both tests-systems a broad spectrum of T3 concentrations was applied. The obtained results showed absence of genotoxic effects of T3 in bacterial reverse mutation assay and very profound genotoxic effects in human lymphocytes at concentrations higher than 15 ?M. We only observed cytotoxic effects in bacterial system at very high T3 concentrations (300 and 500 ?M). In conclusion, T3 was unable to increase the level of reverse mutations in Ames test both with and without S9 mix. Therefore, it seems that ROS production in mitochondria may be the primary cause of DNA damage caused by T3 in mammalian cells.

Oxygen free radicals in nephrology

1987 ◽  
Vol 10 (6) ◽  
pp. 379-389 ◽  
Author(s):  
C. Canavese ◽  
P. Stratta ◽  
A. Vercellone
Keyword(s):  
Hydrogen Peroxide ◽  
Superoxide Dismutase ◽  
Free Radicals ◽  
Aging Process ◽  
Oxygen Free Radicals ◽  
Membrane Lipids ◽  
Potential Toxicity ◽  
Practical Possibility ◽  
Clinical Verification ◽  
Hydroxyl Hydrogen

For living creatures with an aerobic metabolism, the univalent reduction of oxygen can lead to formation within the cell of intermediate products with marked chemical instability and strong potential toxicity. These are the free radicals (FR) superoxide and hydroxyl, hydrogen peroxide and the singlet 1O2. Their toxicity is primarily expressed through the peroxidation of membrane lipids, resulting in mitochondrial, lysosomal and parietal damage. It is enhanced by the presence of metals in trace amounts. Imbalance between the production of FR and the availability of FR scavengers (superoxide dismutase, catalase, glutathione peroxidase, etc.) may underlie different human pathologies. FR have been thought to play a part in inflammation; the aging process, carcinomatous transformations, damage due to recirculation and autoimmune diseases. As far as the kidney is concerned, the intervention of FR has been demonstrated or can be postulated in various contexts in the light of what has been observed in other pathologies: immunological nephritis, toxic nephropathies, microthrombotic and microangiopathic processes, damage caused by post-ischemic reflow, and problems in the preservation and rejection of transplants. FR have also been incriminated in lung lesions following intradialytic leukostasis and some aspects of toxicity ascribable to uremia. Subject to the precautions imposed by the need for theoretical, experimental and clinical verification, FR biochemistry offers new keys to the interpretation of a variety of kidney pathologies and opens up new prospects for treatment, both through a better understanding of the mechanism of action of drugs already known and employed, and with regard to the practical possibility of using alternative or combined forms of therapy.

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