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.

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.

Alterations in cardiac lysosomal hydrolases following induction of the calcium paradox

1987 ◽  
Vol 65 (11) ◽  
pp. 2175-2181 ◽  
Author(s):  
Michael J. B. Kutryk ◽  
Naranjan S. Dhalla
Keyword(s):  
Lysosomal Enzyme ◽  
Enzyme Activities ◽  
Lysosomal Enzymes ◽  
Cell Damage ◽  
Calcium Paradox ◽  
Free Medium ◽  
Lysosomal Hydrolases ◽  
Cardiac Damage ◽  
Rat Hearts ◽  
Reperfusion Period

Although perfusion of the heart with calcium-free medium for a brief period followed by reperfusion with calcium-containing medium results in marked structural derangements (calcium paradox), the mechanisms for this cell damage are far from clear. Since activation of lysosomal enzymes has been associated with pathological damage, it was the purpose of this study to examine alterations in the activities of several lysosomal enzymes in rat hearts subjected to calcium paradox. No significant changes in the activities of (β-acetylglucosaminidase, β-galactosidase, α-mannosidase, or acid phosphatase were seen in the homogenates of hearts exposed to the calcium paradox. However, there were dramatic alterations in the lysosomal enzyme activities in the sedimentable and nonsedimentable fractions during calcium paradox. The lysosomal enzyme activities were also detected in the perfusate collected during reperfusion with calcium-containing medium. These changes occurred during the reperfusion period since no alterations were apparent after calcium-free perfusion and were dependent upon the time of reperfusion with medium containing Ca2+ as well as the time of perfusion with Ca2+ -free medium before inducing Ca2+ paradox. These data indicate that alterations in lysosomal enzymes owing to reinstitution of calcium in Ca2+-deprived hearts may occur as a part of cardiac damage and general cellular disintegration.

LIPID PEROXIDATION, OXYGEN RADICALS, CELL DAMAGE, AND ANTIOXIDANT THERAPY

The Lancet ◽  
1984 ◽  
Vol 323 (8391) ◽  
pp. 1396-1397 ◽  
Author(s):  
B. Halliwell ◽  
JohnM.C. Gutteridge
Keyword(s):  
Lipid Peroxidation ◽  
Oxygen Radicals ◽  
Cell Damage ◽  
Antioxidant Therapy

Targeting xanthine oxidase by natural products as a therapeutic approach for mental disorders

2020 ◽  
Vol 26 ◽  
Author(s):  
Miquel Martorell ◽  
Xavier Lucas ◽  
Pedro Alarcón-Zapata ◽  
Xavier Capó ◽  
Maria Magdalena Quetglas-Llabrés ◽  
...  
Keyword(s):  
Mental Disorders ◽  
Small Molecules ◽  
Xanthine Oxidase ◽  
Cell Damage ◽  
Bipolar Affective Disorder ◽  
Oxidative Reaction ◽  
Mental Diseases ◽  
Potential Therapeutic Application ◽  
Increased Activity ◽  
Dietary Flavonoids

: Mental disorders comprise diverse human pathologies including depression, bipolar affective disorder, schizophrenia, and dementia that affect millions of people around the world. The causes of mental disorders are unclear but growing evidence suggests that oxidative stress and the purine/adenosine system play a key role in their development and progression. Xanthine oxidase (XO) is a flavoprotein enzyme essential for the catalysis of the oxidative hydroxylation of purines -hypoxanthine and xanthine- to generate uric acid. As a consequence of the oxidative reaction of XO, reactive oxygen species (ROS) such as superoxide and hydrogen peroxide are produced and, further, contribute to the pathogenesis of mental disorders. Altered XO activity has been associated with free radical-mediated neurotoxicity inducing cell damage and inflammation. Diverse studies reported a direct association between an increased activity of XO and diverse mental diseases including depression or schizophrenia. Small-molecule inhibitors, such as the well-known allopurinol, and dietary flavonoids, can modulate the XO activity and subsequent ROS production. In the present work, we review the available literature on XO inhibition by small molecules and their potential therapeutic application in mental disorders. In addition, we discuss the chemistry and molecular mechanism of XO inhibitors, as well as the use of structure-based and computational methods to design specific inhibitors with the capability of modulating XO activity.

Mechanisms of Nickel-Induced Cell Damage in Allergic Contact Dermatitis and Nutritional Intervention Strategies

2020 ◽  
Vol 20 (7) ◽  
pp. 1010-1014 ◽  
Author(s):  
Dana Filatova ◽  
Christine Cherpak
Keyword(s):  
Lipid Peroxidation ◽  
Contact Dermatitis ◽  
Oxidative Damage ◽  
Allergic Contact Dermatitis ◽  
Cell Damage ◽  
Consumer Products ◽  
The Body ◽  
Cellular Damage ◽  
Nutritional Interventions ◽  
Allergic Contact

Background: Hypersensitivity to nickel is a very common cause of allergic contact dermatitis since this metal is largely present in industrial and consumer products as well as in some commonly consumed foods, air, soil, and water. In nickel-sensitized individuals, a cell-mediated delayed hypersensitivity response results in contact to dermatitis due to mucous membranes coming in long-term contact with nickel-containing objects. This process involves the generation of reactive oxidative species and lipid peroxidation-induced oxidative damage. Immunologically, the involvement of T helper (h)-1 and Th-2 cells, as well as the reduced function of T regulatory cells, are of importance. The toxicity, mutagenicity, and carcinogenicity of nickel are attributed to the generation of reactive oxygen species and induction of oxidative damage via lipid peroxidation, which results in DNA damage. Objective: The aim of this research is to identify nutritionally actionable interventions that can intercept nickel-induced cell damage due to their antioxidant capacities. Conclusion: Nutritional interventions may be used to modulate immune dysregulation, thereby intercepting nickel-induced cellular damage. Among these nutritional interventions are a low-nickel diet and an antioxidant-rich diet that is sufficient in iron needed to minimize nickel absorption. These dietary approaches not only reduce the likelihood of nickel toxicity by minimizing nickel exposure but also help prevent oxidative damage by supplying the body with antioxidants that neutralize free radicals.

Sign in / Sign up

Export Citation Format

Share Document