Abstract 13916: A Novel Biomarker of Oxidative Stress is Predictive of Incident Death and Myocardial Infarction in Patients with Coronary Artery Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Riyaz S Patel ◽  
Nima Ghasemzadeh ◽  
Danny J Eapen ◽  
Salman Sher ◽  
Shawn Arshad ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
High Performance ◽  
Composite Endpoint ◽  
Cardiovascular Death ◽  
Adverse Outcomes ◽  
Cellular Damage ◽  
Free Radical Scavengers ◽  
C Statistic ◽  
Artery Disease

Introduction: Oxidative stress (OS) is implicated in cellular damage and atherosclerosis, yet clinical experience of free radical scavengers has been uniformly disappointing, promoting the concept that clinically important OS may be mediated by alternative non-free radical processes. Hypothesis: We hypothesized that novel aminothiol markers of non-free radical mediated OS would predict incident adverse outcomes in patients at high risk for CAD Methods: 1411 consecutive patients undergoing coronary angiography (mean age 63 years, male 66%), were recruited from the Emory Cardiovascular Biobank study. Plasma levels of reduced (cysteine and glutathione) and oxidized (cystine and glutathione disulphide) aminothiols were measured by high performance liquid chromatography at baseline and patients followed prospectively for a primary composite endpoint of death or non-fatal MI. Results: During a mean follow up of 3.9± 2.2 years, 19% died or suffered a non-fatal MI. The adjusted hazard ratios for all cause death/MI based on high vs low cut-points for the oxidized disulphide cystine was 1.65 (95% CI, 1.27-2.15); for reduced glutathione was 0.69 (0.52-0.92), and for the ratio of cystine/glutathione was 1.79 (1.39-2.30). Compared to a model containing clinical risk factors and CRP, addition of the cystine/glutathione ratio improved the C-Statistic (p=0.03) and also correctly reclassified 17% of events and 23% of non-events. When combined with high/low CRP into a 3 level multi-marker score, those with 2 high markers had an annualized event rate of 12.8% compared to 4.5% and 1.4% for those with 1 raised marker or none, respectively. Similar associations were found for all-cause and cardiovascular death endpoints and also in stratified analysis for those with and without significant CAD. Conclusions: A high extracellular oxidant burden and reduced intracellular antioxidant capacity quantified by the plasma aminothiols, cystine, glutathione and their respective ratio, is associated with adverse events in patients with CAD, a finding that is independent of and additive to any inflammatory burden. Further studies are needed to validate these findings, which support an alternative model of oxidative stress independent of free radical biology.

scholarly journals Mechanistic Insight into Antimicrobial and Antioxidant Potential of Jasminum Species: A Herbal Approach for Disease Management

Plants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1089
Author(s):  
Acharya Balkrishna ◽  
Akansha Rohela ◽  
Abhishek Kumar ◽  
Ashwani Kumar ◽  
Vedpriya Arya ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Drug Resistance ◽  
Free Radicals ◽  
Free Radical ◽  
Microbial Pathogens ◽  
Free Radical Scavengers ◽  
Bioactive Constituents ◽  
Global Issues ◽  
Iridoid Glucosides ◽  
Insight Into

Drug resistance among microbial pathogens and oxidative stress caused by reactive oxygen species are two of the most challenging global issues. Firstly, drug-resistant pathogens cause several fatalities every year. Secondly aging and a variety of diseases, such as cardiovascular disease and cancer, are associated with free radical generated oxidative stress. The treatments currently available are limited, ineffective, or less efficient, so there is an immediate need to tackle these issues by looking for new therapies to resolve resistance and neutralize the harmful effects of free radicals. In the 21st century, the best way to save humans from them could be by using plants as well as their bioactive constituents. In this specific context, Jasminum is a major plant genus that is used in the Ayurvedic system of medicine to treat a variety of ailments. The information in this review was gathered from a variety of sources, including books, websites, and databases such as Science Direct, PubMed, and Google Scholar. In this review, a total of 14 species of Jasminum have been found to be efficient and effective against a wide variety of microbial pathogens. In addition, 14 species were found to be active free radical scavengers. The review is also focused on the disorders related to oxidative stress, and it was concluded that Jasminum grandiflorum and J. sambac normalized various parameters that were elevated by free radical generation. Alkaloids, flavonoids (rutoside), terpenes, phenols, and iridoid glucosides are among the main phytoconstituents found in various Jasminum species. Furthermore, this review also provides insight into the mechanistic basis of drug resistance, the generation of free radicals, and the role of Jasminum plants in combating resistance and neutralizing free radicals.

scholarly journals Effects of Caloric Restriction on Cardiac Oxidative Stress and Mitochondrial Bioenergetics: Potential Role of Cardiac Sirtuins

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ken Shinmura
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Oxidative Damage ◽  
Caloric Restriction ◽  
Functional Decline ◽  
Cellular Damage ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Stress Theory

The biology of aging has not been fully clarified, but the free radical theory of aging is one of the strongest aging theories proposed to date. The free radical theory has been expanded to the oxidative stress theory, in which mitochondria play a central role in the development of the aging process because of their critical roles in bioenergetics, oxidant production, and regulation of cell death. A decline in cardiac mitochondrial function associated with the accumulation of oxidative damage might be responsible, at least in part, for the decline in cardiac performance with age. In contrast, lifelong caloric restriction can attenuate functional decline with age, delay the onset of morbidity, and extend lifespan in various species. The effect of caloric restriction appears to be related to a reduction in cellular damage induced by reactive oxygen species. There is increasing evidence that sirtuins play an essential role in the reduction of mitochondrial oxidative stress during caloric restriction. We speculate that cardiac sirtuins attenuate the accumulation of oxidative damage associated with age by modifying specific mitochondrial proteins posttranscriptionally. Therefore, the distinct role of each sirtuin in the heart subjected to caloric restriction should be clarified to translate sirtuin biology into clinical practice.

scholarly journals HPTLC study to determine the antioxidant activity of dried leaves of Portulaca oleracea L.

2021 ◽  
Vol 12 (1) ◽  
pp. 254-261
Author(s):  
Kesri Nandan Sharma ◽  
Nitu Bhatnagar
Keyword(s):  
Free Radical ◽  
High Performance ◽  
Radical Scavenging ◽  
Portulaca Oleracea ◽  
Free Radical Scavengers ◽  
Stable Free Radical ◽  
Methanolic Extracts ◽  
Straightforward Method ◽  
Anti Oxidant ◽  
B Complex Vitamins

This present study involves the assessment of the anti-oxidant activity study of the sample which was obtained from the methanolic extracts of dried leaves of Portulaca Oleracea L.(common name Purslane). Purslane is a rich source of Vitamin A, Vitamin-C and some other B-complex vitamins like riboflavin, niacin, pyridoxine and carotenoids which are known powerful natural anti-oxidants.  Anti-oxidants are compounds that inhibit oxidation. This methanolic extract of leaves was evaluated for the determination of its anti-oxidant efficiency by using 1,1–diphenyl-2-picryl-hydrazyl (DPPH) by using Silica TLC plates on Camag High-Performance Thin Layer Chromatography (HPTLC) system using visionCATS software. Densitograms and chromatographs obtained show the presence of anti-oxidant activity. It is a rapid, inexpensive and straightforward method to measure anti-oxidant properties of substances after separation by HPTLC. It involves the use of the free radical, 2, 2-Diphenyl-1- picrylhydrazyl (DPPH) which is widely used to test the ability of compounds to act as free radical scavengers or hydrogen donors and to evaluate anti-oxidant activity. When Anti-oxidants substances react with DPPH, which is a stable free radical becomes paired off in the presence of a hydrogen donor (e.g., a free radical scavenging anti-oxidant) and is reduced to the DPPHH. As a consequence, the absorbance's decreased from the DPPH.   

scholarly journals Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease

2021 ◽  
pp. ASN.2021020167
Author(s):  
Glenn Chertow ◽  
Priya Vart ◽  
Niels Jongs ◽  
Robert Toto ◽  
Jose Luis Gorriz ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Adverse Events ◽  
Controlled Trial ◽  
Composite Endpoint ◽  
Cardiovascular Death ◽  
Adverse Outcomes ◽  
Serious Adverse Events ◽  
Stage 4 ◽  
Cardiovascular Endpoint

Background In the Dapagliflozin And Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized placebo-controlled trial, the sodium-glucose cotransporter 2 inhibitor dapagliflozin significantly reduced risk of kidney failure and prolonged survival in CKD patients with or without type 2 diabetes. Methods In this prespecified analysis of dapagliflozin's effects in patients with stage 4 CKD (eGFR<30 mL/min per 1.73m2) at baseline, we randomized adults with eGFR of 25-75 mL/min per 1.73m2 and urinary albumin-to-creatinine ratio of 200-5000 mg/g to receive dapagliflozin 10 mg/day or placebo. The primary outcome was a composite of time to ≥50% sustained decline in eGFR, end-stage kidney disease, or kidney or cardiovascular death. Secondary outcomes were a kidney composite (same as the primary endpoint but without cardiovascular death), a composite of cardiovascular death or heart failure hospitalization, and all-cause death. Results A total of 293 participants received dapagliflozin and 331 received placebo. Relative to placebo, dapagliflozin was associated with reductions in the primary composite endpoint (hazard ratio [HR], 0.73; 95% confidence interval [95% CI], 0.53 to 1.0), the kidney endpoint (HR, 0.71; 95% CI, 0.49 to 1.02), the cardiovascular endpoint (HR, 0.83; 95% CI, 0.45 to 1.53), and the mortality endpoint (HR, 0.68; 95% CI, 0.39 to 1.21). The eGFR slope declined by 2.15 and 3.38 mL/min per 1.73m2 per year in the dapagliflozin and placebo groups, respectively (P=0.005). Patients treated with dapagliflozin or placebo had similar rates of serious adverse events and adverse events of interest. Conclusions Among patients with stage 4 CKD and albuminuria, dapagliflozin's benefits were consistent with those observed in the DAPA-CKD trial overall, with no evidence of increased risks.

scholarly journals Lessons learned from the DAPA-HF trial concerning the mechanisms of benefit of SGLT2 inhibitors on heart failure events in the context of other large-scale trials nearing completion

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Milton Packer
Keyword(s):  
Heart Failure ◽  
Large Scale ◽  
Cardiovascular Death ◽  
Sglt2 Inhibitors ◽  
Adverse Outcomes ◽  
Lessons Learned ◽  
Reduced Ejection Fraction ◽  
Sodium Glucose Cotransporter ◽  
Patients With Diabetes ◽  
Artery Disease

Abstract Four large-scale trials in type 2 diabetes have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors prevent the occurrence of serious heart failure events. Additionally, the DAPA-HF trial demonstrated a benefit of dapagliflozin to reduce major adverse outcomes in patients with established heart failure with a reduced ejection fraction. The trial sheds light on potential mechanisms. In DAPA-HF, the benefits of dapagliflozin on heart failure were seen to a similar extent in both patients with or without diabetes, thus undermining the hypothesis that these drugs mitigate glycemia-related cardiotoxicity. The action of SGLT2 inhibitors to promote ketogenesis is also primarily a feature of the action of these drugs in patients with diabetes, raising doubts that enhanced ketogenesis contributes to the benefit on heart failure. Also, dapagliflozin does not have a meaningful effect to decrease circulating natriuretic peptides, and it did not potentiate the actions of diuretics in DAPA-HF; moreover, intensification of diuretics therapy does not reduce cardiovascular death, questioning a benefit of SGLT2 inhibitors that is mediated by an action on renal sodium excretion. Finally, although hematocrit increases with SGLT2 inhibitors might favorably affect patients with coronary artery disease, in DAPA-HF, the benefit of dapagliflozin was similar in patients with or without an ischemic cardiomyopathy; furthermore, increases in hematocrit do not favorably affect the clinical course of patients with heart failure. Therefore, the results of DAPA-HF do not support many currently-held hypotheses about the mechanism of action of SGLT2 inhibitors in heart failure. Ongoing trials are likely to provide further insights.

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